Rienzi asserts, based on this study [1], that 'Personal "self-identification" is not enough. Genetic analyses of ancestry are required.' Rienzi clearly implies this study of "African Americans" indicates a need for individual genetic ancestry analysis of white Americans--an absurd conclusion.
Studies have repeatedly shown American blacks average ~20% European admixture, while white Americans show minimal if any non-European admixture. Gene flow was overwhelmingly one way.
It is no surprise that among American blacks "self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry". The overwhelming majority of American blacks have "African" (black) parents and grandparents. No doubt most of Aframs' European genes entered the Afram gene pool more than 3 generation ago. Aframs without recent white ancestors may range from light-skinned to coal-black. We see no such variations in the phenotypes of white Americans.
Additionally, most white Americans who care to can construct pedigrees for themselves much deeper than three generations.
While I personally find genetic ancestry analysis interesting, and look forward to further developments in the field, as of now I see nothing of benefit for the overwhelming majority of white Americans in any commercially available test of individual admixture.
[1] Comparing genetic ancestry and self-described race in african americans born in the United States and in Africa. Yaeger R, Avila-Bront A, Abdul K, Nolan PC, Grann VR, Birchette MG, Choudhry S, Burchard EG, Beckman KB, Gorroochurn P, Ziv E, Consedine NS, Joe AK. Cancer Epidemiol Biomarkers Prev 2008;17(6):1329-38
More ancient DNA results from Xinjiang
I'm unfamiliar with the site and I haven't read the paper, but based on the dates mentioned (~500 BC to 1 AD) these results again most likely have little or no bearing on the question or the origins of the older, Northern European-looking mummies (which date to as early as ~1800 BC).
Sci China C Life Sci. 2008 Mar;51(3):205-13.
Mitochondrial DNA analysis of human remains from the Yuansha site in Xinjiang, China.
Gao S, Cui Y, Yang Y, Duan R, Abuduresule I, Mair VH, Zhu H, Zhou H.
Laboratory of Ancient DNA, Research Center for Chinese Frontier Archaeology, Jilin University, Changchun, 130012, China.
The Yuansha site is located in the center of the Taklimakan Desert of Xinjiang, in the southern Silk Road region. MtDNA was extracted from fifteen human remains excavated from the Yuansha site, dating back 2,000-2,500 years. Analysis of the phylogenetic tree and the multidimensional scaling (MDS) reveals that the Yuansha population has relatively close relationships with the modern populations of South Central Asia and Indus Valley, as well as with the ancient population of Chawuhu.
PMID: 18246308 [PubMed - indexed for MEDLINE]
Sci China C Life Sci. 2008 Mar;51(3):205-13.
Mitochondrial DNA analysis of human remains from the Yuansha site in Xinjiang, China.
Gao S, Cui Y, Yang Y, Duan R, Abuduresule I, Mair VH, Zhu H, Zhou H.
Laboratory of Ancient DNA, Research Center for Chinese Frontier Archaeology, Jilin University, Changchun, 130012, China.
The Yuansha site is located in the center of the Taklimakan Desert of Xinjiang, in the southern Silk Road region. MtDNA was extracted from fifteen human remains excavated from the Yuansha site, dating back 2,000-2,500 years. Analysis of the phylogenetic tree and the multidimensional scaling (MDS) reveals that the Yuansha population has relatively close relationships with the modern populations of South Central Asia and Indus Valley, as well as with the ancient population of Chawuhu.
PMID: 18246308 [PubMed - indexed for MEDLINE]
Some ancient DNA results from the Tarim Basin
Note: some clown references this paper on Wikipedia in the following context:
In fact, this study has no bearing on the origins of the Northern Europoid "Tarim mummies". Sampul is a much later site, which according to physical anthropologists was populated primarily by Central Asian "Eastern Mediterranean" types. Mallory and Mair discuss the findings of Han Kangxin:
Progress in Natural Science, Volume 17, Number 8, pp. 927-933(7)
Mitochondrial DNA analysis of ancient Sampula population in Xinjiang
Xie Chengzhi Li Chunxiang Cui Yinqiu Cai Dawei Wang Haijing Zhu Hong Zhou Hui
Abstract: The archaeological site of Sampula cemetery was located about 14 km to the southwest of the Luo County in Xinjiang Khotan, China, belonging to the ancient Yutian kingdom. 14C analysis showed that this cemetery was used from 217 B.C. to 283 A.D. Ancient DNA was analyzed by 364 bp of the mitochondrial DNA hypervariable region I (mtDNA HVR-I), and by six restriction fragment length polymorphism (RFLP) sites of mtDNA coding region. We successfully extracted and sequenced intact stretches of maternally inherited mtDNA from 13 out of 16 ancient Sampula samples. The analysis of mtDNA haplogroup distribution showed that the ancient Sampula was a complex population with both European and Asian characteristics. Median joining network of U3 sub-haplogroup and multi-dimensional scaling analysis all showed that the ancient Sampula had maternal relationship with Ossetian and Iranian.
Keywords: ancient DNA mitochondrial DNA Sampula ancient populations
[link]
The authors detect the following haplogroups: U3 (in four individuals), N (x2), C (x2), B, F1a, G, M, and T2.
The cemetery at Yanbulaq contained 29 mummies which date from 1800–500 BC, 21 of which are Caucasoid—the earliest Caucasoid mummies found in the Tarim Basin—and eight of which are of the same Caucasoid physical type found at Qäwrighul.[1]:237 . However, more recent genetic studies painted a more complex picture (Xie et al., 2007). It showed both european and asian characteristics.
In fact, this study has no bearing on the origins of the Northern Europoid "Tarim mummies". Sampul is a much later site, which according to physical anthropologists was populated primarily by Central Asian "Eastern Mediterranean" types. Mallory and Mair discuss the findings of Han Kangxin:
The Qäwrighul remains are relatively homogeneous and they exhibit features associated with a type known as Proto-Europoid, a rather robust Caucasoid, especially well represented in Northern Europe and the steppelands and forest-steppe of Russia and the Ukraine. Similar remains occur in the Bronze Age cemeteries of southern Siberia, Kazakhstan, Central Asia and the Lower Volga. [. . .]
The next oldest remains derive from the Yanbulaq cemetery near Humul (Hami), situated to the northeast of Qäwrighul and the easternmost cemetery investigated. Here Han Kangxin identified 21 of the 29 complete skulls as Mongoloids and these are the earliest definite evidence of Mongoloids in East Central Asia. The remaining skulls, however, belonged to Caucasoids who are closest to those from Qäwrighul and point to the same general direction for their origins, i.e. the steppelands to the north and west.
The single skull recovered from among the inhumation burials at Shambalay near Tahkurgan in the far west of the Tarim Basin has been compared with the type that spanned the Mediterranean across Central Asia; this type also includes the Saka tribes of the southern Pamirs.
A much larger sample of 58 skulls was recovered from one of the mass graves at Alwighul in the Tangri Tagh (Tian Shan). Here Han distinguishes two Caucasoids types: the Eastern Mediterranean or Indo-Afghan type with their long and high skulls and the broader and rounder skulls of the Pamir-Ferghana type; Han also identified hybrids of these two subtypes as well as some evidence of Mongoloid admixture. By now, the attentive reader will know we owe another caveat; the three physical types employed by Han Kangxin -- Proto-Europoids, Indo-Afghans and Pamir-Ferghanans -- are largely relabelled Nordics, Mediterraneans, and Alpines, terms that send shivers of apprehension down the spines of Western biological anthropologists.
[. . .]
The Sampul cemetery provides us with our only physical anthropological evidence of the southern Silk Road in the vicinity of Khotan. Although the cemetery contained various individual graves employing some form of log coffin, all the burials examined derive from the group graves which date to the first centuries BC. Han Kangxin has identified the remains as belonging to the same Indo-Afghan type that one encounters among the Saka of the southern Pamirs.
[pp. 236-239; The Tarim Mummies]
Progress in Natural Science, Volume 17, Number 8, pp. 927-933(7)
Mitochondrial DNA analysis of ancient Sampula population in Xinjiang
Xie Chengzhi Li Chunxiang Cui Yinqiu Cai Dawei Wang Haijing Zhu Hong Zhou Hui
Abstract: The archaeological site of Sampula cemetery was located about 14 km to the southwest of the Luo County in Xinjiang Khotan, China, belonging to the ancient Yutian kingdom. 14C analysis showed that this cemetery was used from 217 B.C. to 283 A.D. Ancient DNA was analyzed by 364 bp of the mitochondrial DNA hypervariable region I (mtDNA HVR-I), and by six restriction fragment length polymorphism (RFLP) sites of mtDNA coding region. We successfully extracted and sequenced intact stretches of maternally inherited mtDNA from 13 out of 16 ancient Sampula samples. The analysis of mtDNA haplogroup distribution showed that the ancient Sampula was a complex population with both European and Asian characteristics. Median joining network of U3 sub-haplogroup and multi-dimensional scaling analysis all showed that the ancient Sampula had maternal relationship with Ossetian and Iranian.
Keywords: ancient DNA mitochondrial DNA Sampula ancient populations
[link]
The authors detect the following haplogroups: U3 (in four individuals), N (x2), C (x2), B, F1a, G, M, and T2.
Oceania: tracing population history and adaptation with genome-wide SNP data
MBE Advance Access published online on June 3, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn128
Gene Flow and Natural Selection in Oceanic Human Populations, Inferred from Genome-wide SNP Typing
Ryosuke Kimura1,*, Jun Ohashi2, Yasuhiro Matsumura3, Minato Nakazawa4, Tsukasa Inaoka5, Ryutaro Ohtsuka6, Motoki Osawa1 and Katsushi Tokunaga2
It is suggested that the major prehistoric human colonizations of Oceania occurred twice, namely, about 50,000 and 4,000 years ago. The first settlers are considered as ancestors of indigenous people in New Guinea and Australia. The second settlers are Austronesian-speaking people who dispersed by voyaging in the Pacific Ocean. In this study, we performed genome-wide SNP typing on an indigenous Melanesian (Papuan) population, Gidra, and a Polynesian population, Tongans, by using the Affymetrix 500K assay. The SNP data were analyzed together with the data of the HapMap samples provided by Affymetrix. In agreement with previous studies, our phylogenetic analysis indicated that indigenous Melanesians are genetically closer to Asians than to Africans and European Americans. Population structure analyses revealed that the Tongan population is genetically originated from Asians at 70% and indigenous Melanesians at 30%, which thus supports the so-called "Slow train" model. We also applied the SNP data to genome-wide scans for positive selection by examining haplotypic variation, and identified many candidates of locally selected genes. Providing a clue to understand human adaptation to environments, our approach based on evolutionary genetics must contribute to revealing unknown gene functions as well as functional differences between alleles. Conversely, this approach can also shed some light onto the invisible phenotypic differences between populations.
Key Words: adaptive evolution • gene flow • human genome • SNP • Oceania
http://mbe.oxfordjournals.org/cgi/content/short/msn128v1?rss=1
Molecular Biology and Evolution, doi:10.1093/molbev/msn128
Gene Flow and Natural Selection in Oceanic Human Populations, Inferred from Genome-wide SNP Typing
Ryosuke Kimura1,*, Jun Ohashi2, Yasuhiro Matsumura3, Minato Nakazawa4, Tsukasa Inaoka5, Ryutaro Ohtsuka6, Motoki Osawa1 and Katsushi Tokunaga2
It is suggested that the major prehistoric human colonizations of Oceania occurred twice, namely, about 50,000 and 4,000 years ago. The first settlers are considered as ancestors of indigenous people in New Guinea and Australia. The second settlers are Austronesian-speaking people who dispersed by voyaging in the Pacific Ocean. In this study, we performed genome-wide SNP typing on an indigenous Melanesian (Papuan) population, Gidra, and a Polynesian population, Tongans, by using the Affymetrix 500K assay. The SNP data were analyzed together with the data of the HapMap samples provided by Affymetrix. In agreement with previous studies, our phylogenetic analysis indicated that indigenous Melanesians are genetically closer to Asians than to Africans and European Americans. Population structure analyses revealed that the Tongan population is genetically originated from Asians at 70% and indigenous Melanesians at 30%, which thus supports the so-called "Slow train" model. We also applied the SNP data to genome-wide scans for positive selection by examining haplotypic variation, and identified many candidates of locally selected genes. Providing a clue to understand human adaptation to environments, our approach based on evolutionary genetics must contribute to revealing unknown gene functions as well as functional differences between alleles. Conversely, this approach can also shed some light onto the invisible phenotypic differences between populations.
Key Words: adaptive evolution • gene flow • human genome • SNP • Oceania
http://mbe.oxfordjournals.org/cgi/content/short/msn128v1?rss=1
Isotopic analysis of an LBK mass grave
The Telegraph reports the study as follows:Neolithic men were prepared to fight for their women
[. . .]
Many archaeologists have argued that women have long motivated cycles of violence and blood feuds throughout history but there has really been no solid archaeological evidence to support this view.
Now a relatively new method has been used to work out the origins of the victims tossed into a mass grave of skeletons, and so distinguish one tribe from another, revealing that neighbouring tribes were prepared to kill their male rivals to secure their women some 7000 years ago.
The Durham University research, described in the academic journal Antiquity, focused on 34 skeletons found buried in the village of Talheim in the south-west of Germany.
[. . .]
Lead author Dr Alex Bentley says the simplest explanation is that the women of one tribe were captured.
"It seems this community was specifically targeted, as could happen in a cycle of revenge between rival groups. Although resources and population were undoubtedly factors in central Europe around that time, women appear to be the immediate reason for the attack.
"Our analysis points to the local women being regarded as somehow special and were therefore kept alive."
Antiquity
Volume: 82 Number: 316 Page: 290–304
Isotopic signatures and hereditary traits: snapshot of a Neolithic community in Germany
R. Alexander Bentley1, Joachim Wahl2, T. Douglas Price3 and Tim C. Atkinson4
1Department of Anthropology, Durham University, 43 Old Elvet, Durham DH1 3HN, UK (Email: r.a.bentley@durham.ac.uk) 2RP Stuttgart, Landesamt für Denkmalpflege, Osteologie, Stromeyersdorfstraße 3, D-78467, Konstanz, Germany (Email: Joachim.Wahl@rps.bwl.de) 3Department. of Anthropology, University of Wisconsin, 1180 Observatory Dr., Madison, WI 53706-1393, USA (Email: tdprice@wisc.edu) 4Department of Earth Sciences, University College London, Gower Street, London WC1E 6BT, UK (Email: t.atkinson@ucl.ac.uk)
A group of Linearbandkeramik people at Talheim, Germany were previously found to have died at the same time, probably in a massacre, and the authors were able to ask some searching questions of their skeletons. The isotope signatures of strontium, oxygen and carbon, which gave information on diet and childhood region, showed up three groups which correlated with hereditary traits (derived previously from the analysis of the teeth). In the local group, there were many local children but no adult women, suggesting they had been selectively taken alive at the time of the massacre. Another group, with isotope signatures derived from upland areas, includes two men who may have been closely related. A third group has a composition suggestive of a nuclear family. The variations of one type of isotope signature with another suggested subtle interpretations, such as transhumance, and a probable labour division in the community between stockholders and cultivators. Here we see the ever-growing potential of these new methods for writing the ‘biographies’ of prehistoric skeletons.
Keywords: Neolithic, Germany, LBK, Talheim, isotope analysis, hereditary traits, trans-humance
http://www.antiquity.ac.uk/ant/082/ant0820290.htm
Hydraulic cement: Thank the English, not the Romans
[re: hysterical Medocentrist outburst elsewhere]Portland cement as widely used today was originally formulated by Englishman William Aspdin, building on the work of other Englishmen, including his father Joseph Aspdin and, ultimately, John Smeaton:
Smeaton investigated the cementing properties of various mortars, made from lime obtained from various locations, and discovered that the best mortars were made from the calcination of limes that contained considerable proportions of clay minerals (argillaceous lime). This was the first occasion that the importance of clay mixed with the lime had been recognized in the formation of a hydraulic setting cement. It was found that limes that did not dissolve completely in nitric acid (clay being insoluble in the acid) possessed good hydraulic properties (Kohlhaas, 1983). The cementitious agent Smeaton finally used was made from such a clay containing lime which was mixed with an equal quantity of pozzolana (Lea, 1970). The lighthouse that he constructed stood for 123 years until 1879 and only failed when its foundations were undermined by the sea. Smeaton's conclusions about the importance of the presence of clay were not published until after his death in 1792. Smeaton was the first to call himself a civil engineer (as distinct from a military engineer). In the preface to his book, Hydraulischen Moertel, W Michaelis stated in 1869 (in translation):A century has elapsed since the famous Smeaton completed the building of the Eddystone Lighthouse. Not only the seafaring but for all humanity stands as a true signal of blessed work, a light in the dark night. From the scientific point of view it illuminated the darkness of nearly 2000 years.The cement was called 'Roman cement' although it in no way resembled the true Roman cement, except for its hydraulic setting reactions.
The errors which came to us from the Romans and which were shared even by the excellent Belidor, were dispersed.
The Eddystone Lighthouse is the foundation upon which our knowledge of hydraulic mortars has been built and is the chief pillar of modern construction. Smeaton freed us from the shackles of tradition by showing us that the purest and hardest limestone is not the best, at least for hydraulic purposes, and that the source of the hydraulicity of lime mortar must be sought in the argillacrious admixtures (Draffin, 1976).
[Mary S. J. Gani; Cement and Concrete; p. 5]
The Romans ceased building with high-quality concrete by around A.D. 300. Our modern knowledge of cement owes nothing to them.
Cement was used from the decline of the Empire and through the Middle Ages, but none of it was any good until comparatively recent times (Davey, 1961). [. . .]
In this case, it was not that a Roman secret was lost, rather that the Romans, who did no testing, never learned what they had. The very idea of testing is comparatively recent, and the engineer John Smeaton, who tested samples for the construction of the Eddystone Light in the years 1756– 1759 (Davey, 1961) is, I suspect, the first man on the planet deliberately to test cements of differing compositions.
[Thomas Nelson Winter. Roman Concrete: The Ascent, Summit, and Decline of an Art. Transactions of the Nebraska Academy of Sciences 7 (1979), pp. 137-143.]
Europeans more highly evolved, not "genetically weaker"
This part of John Hawks' most recent post is worth pointing out:
What is amazing to me is that these same geneticists embrace hypotheses of population history that cannot possibly have happened. The other geneticists quoted in the article, Carlos Bustamante and his graduate student Kirk Lohmueller, wrote a paper earlier this spring arguing that deleterious mutations have reached high frequency in Europeans (moreso than Africans) because of a bottleneck during European history. The press reported this work as "Whites genetically weaker than blacks, study finds." The hypothesis in the paper is that protein-coding sites otherwise conserved in most mammals may differ among humans because of relaxed selection in a bottleneck.
Here's why they're wrong: their bottleneck is impossible. They propose that the European population was a small, isolated population of 5,700 effective individuals from 214,000 years ago up to the Last Glacial Maximum. I suppose I should take some encouragement that they believe Neandertals were European ancestors (because otherwise, where exactly would this small, isolated population of Europeans have lived). But it's still quite impossible -- it implies no gene flow between Africans and Europeans across that entire span. You see, that is the only way that genetic drift can lead to this kind of result -- large differences in frequencies between continents for hundreds of deleterious alleles. It takes a bottleneck of exceptional length, along with complete isolation.
In what has become a troubling trend, these details were hidden away in the online supplementary information of the paper. It is no surprise that most people read only the paper's conclusions, without critically evaluating the methods. But when the assumptions are hidden so that it takes an effort to look at them, you can understand that the paper does not receive the kind of scrutiny that it deserves. These are not obscure laboratory techniques; they are the basic evidence on which the conclusions were based.
Now, Bustamante knows that positive selection has been very important in recent human evolution, because he wrote an important paper on the subject in 2005. I wrote about the paper at the time -- it was one of the works that really got us thinking about acceleration in the first place. So why in the world did their more recent paper adopt such a ridiculous model of population history?
In any event, I don't think that either of these studies from earlier this year are relevant to our acceleration results. They address different aspects of genetic variation. However, acceleration may help to explain the high frequencies of some gene variants conserved in other mammals -- the results explained by Lohmueller and colleagues as relaxed selection under a bottleneck.
The acceleration of recent positive selection would predict that many otherwise conserved gene variants may be segregating in humans, because they are the targets of positive selection. These conserved sites are among those most likely to show a strong sign of recent selection, because adaptive changes on them are necessarily rare (we know they're rare, because they haven't happened very often among other species). Most such sites are still conserved in humans -- it's just not possible to change their function in adaptive ways. But the massive ecological changes of recent human history have created the opportunity for adaptive responses that are not present in other mammalian lineages. We shouldn't be surprised to see that some such changes are currently underway.
Kin selection and the evolution of virulence
Heredity (2008) 100, 484–488; doi:10.1038/sj.hdy.6801093; published online 23 January 2008
Kin selection and the evolution of virulence (pdf)
A Buckling and M A Brockhurst
Social interactions between conspecific parasites are partly dependent on the relatedness of interacting parasites (kin selection), which, in turn, is predicted to affect the extent of damage they cause their hosts (virulence). High relatedness is generally assumed to favour less competitive interactions, but the relationship between relatedness and virulence is crucially dependent on the social behaviour in question. Here, we discuss the rather limited body of experimental work that addresses how kin-selected social behaviours affect virulence. First, if prudent use of host resources (a form of cooperation) maximizes the transmission success of the parasite population, decreased relatedness is predicted to result in increased host exploitation and virulence. Experimental support for this well-established theoretical result is surprisingly limited. Second, if parasite within-host growth rate is a positive function of cooperation (that is, when individuals need to donate public goods, such as extracellular enzymes), virulence is predicted to increase with increasing relatedness. The limited studies testing this hypothesis are broadly consistent with this prediction. Finally, there is some empirical evidence supporting theory that suggests that spiteful behaviours are maximized at intermediate degrees of relatedness, which, in turn, leads to minimal virulence because of the reduced growth rate of the infecting population. We highlight the need for further thorough experimentation on the role of kin selection in the evolution of virulence and identify additional biological complexities to these simple frameworks.
Keywords: experimental evolution, parasite, cooperation, spite, microbe, public goods
Kin selection and the evolution of virulence (pdf)
A Buckling and M A Brockhurst
Social interactions between conspecific parasites are partly dependent on the relatedness of interacting parasites (kin selection), which, in turn, is predicted to affect the extent of damage they cause their hosts (virulence). High relatedness is generally assumed to favour less competitive interactions, but the relationship between relatedness and virulence is crucially dependent on the social behaviour in question. Here, we discuss the rather limited body of experimental work that addresses how kin-selected social behaviours affect virulence. First, if prudent use of host resources (a form of cooperation) maximizes the transmission success of the parasite population, decreased relatedness is predicted to result in increased host exploitation and virulence. Experimental support for this well-established theoretical result is surprisingly limited. Second, if parasite within-host growth rate is a positive function of cooperation (that is, when individuals need to donate public goods, such as extracellular enzymes), virulence is predicted to increase with increasing relatedness. The limited studies testing this hypothesis are broadly consistent with this prediction. Finally, there is some empirical evidence supporting theory that suggests that spiteful behaviours are maximized at intermediate degrees of relatedness, which, in turn, leads to minimal virulence because of the reduced growth rate of the infecting population. We highlight the need for further thorough experimentation on the role of kin selection in the evolution of virulence and identify additional biological complexities to these simple frameworks.
Keywords: experimental evolution, parasite, cooperation, spite, microbe, public goods
Ancient Japan: Jomon vs. Yayoi limb proportions
American Journal of Physical Anthropology; 10.1002/ajpa.20853; Published Online: 16 May 2008
Variation in limb proportions between Jomon foragers and Yayoi agriculturalists from prehistoric Japan
Daniel H. Temple et al.
Keywords: ecogeography, canalization, phenotypic plasticity, Allen's rule, migration
Variation in limb proportions between prehistoric Jomon and Yayoi people of Japan are explored by this study. Jomon people were the descendents of Pleistocene nomads who migrated to the Japanese Islands around 30,000 yBP. Phenotypic and genotypic evidence indicates that Yayoi people were recent migrants to Japan from continental Northeast Asia who likely interbred with Jomon foragers. Limb proportions of Jomon and Yayoi people were compared using RMA regression and Quick-Test calculations to investigate relative variability between these two groups. Cluster and principal components analyses were performed on size-standardized limb lengths and used to compare Jomon and Yayoi people with other groups from various climatic zones. Elongated distal relative to proximal limb lengths were observed among Jomon compared to Yayoi people. Jomon limb proportions were similar to human groups from temperate/tropical climates at lower latitudes, while Yayoi limb proportions more closely resemble groups from colder climates at higher latitudes. Limb proportional similarities with groups from warmer environments among Jomon foragers likely reflect morphological changes following Pleistocene colonization of the Japanese Islands. Cold-derived limb proportions among the Yayoi people likely indicate retention of these traits following comparatively recent migrations to the Japanese Islands. Changes in limb proportions experienced by Jomon foragers and retention of cold-derived limb proportions among Yayoi people conform to previous findings that report changes in these proportions following long-standing evolution in a specific environment. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc.
Variation in limb proportions between Jomon foragers and Yayoi agriculturalists from prehistoric Japan
Daniel H. Temple et al.
Keywords: ecogeography, canalization, phenotypic plasticity, Allen's rule, migration
Variation in limb proportions between prehistoric Jomon and Yayoi people of Japan are explored by this study. Jomon people were the descendents of Pleistocene nomads who migrated to the Japanese Islands around 30,000 yBP. Phenotypic and genotypic evidence indicates that Yayoi people were recent migrants to Japan from continental Northeast Asia who likely interbred with Jomon foragers. Limb proportions of Jomon and Yayoi people were compared using RMA regression and Quick-Test calculations to investigate relative variability between these two groups. Cluster and principal components analyses were performed on size-standardized limb lengths and used to compare Jomon and Yayoi people with other groups from various climatic zones. Elongated distal relative to proximal limb lengths were observed among Jomon compared to Yayoi people. Jomon limb proportions were similar to human groups from temperate/tropical climates at lower latitudes, while Yayoi limb proportions more closely resemble groups from colder climates at higher latitudes. Limb proportional similarities with groups from warmer environments among Jomon foragers likely reflect morphological changes following Pleistocene colonization of the Japanese Islands. Cold-derived limb proportions among the Yayoi people likely indicate retention of these traits following comparatively recent migrations to the Japanese Islands. Changes in limb proportions experienced by Jomon foragers and retention of cold-derived limb proportions among Yayoi people conform to previous findings that report changes in these proportions following long-standing evolution in a specific environment. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc.
Ancient Britons "had geometry skills to rival Pythagoras"
The Independent reports:
(via rogueclassicism)
Stone Age Britons had a sophisticated knowledge of geometry to rival Pythagoras – 2,000 years before the Greek "father of numbers" was born, according to a new study of Stonehenge.
Five years of detailed research, carried out by the Oxford University landscape archaeologist Anthony Johnson, claims that Stonehenge was designed and built using advanced geometry.
The discovery has immense implications for understanding the monument – and the people who built it. It also suggests it is more rooted in the study of geometry than early astronomy – as is often speculated.
Mr Johnson believes the geometrical knowledge eventually used to plan, pre-fabricate and erect Stonehenge was learnt empirically hundreds of years earlier through the construction of much simpler monuments.
[. . .]
The experimental archaeology demonstrates that most of the monument was pre-planned and that the great stones were pre-fabricated off-site and then installed by surveyor-engineers.
"For years people have speculated that Stonehenge was built as a complex astronomical observatory. My research suggests that, apart from mid-summer and mid-winter solar alignments, this was not the case," said Mr Johnson. "It strongly suggests that it was the knowledge of geometry and symmetry which was an important component of the Neolithic belief system."
"It shows the builders of Stonehenge had a sophisticated yet empirically derived knowledge of Pythagorean geometry 2000 years before Pythagoras," he said.
(via rogueclassicism)
Human population history: a reconstruction based on HGDP genome-wide SNP data
From the press release:
Sounds interesting, but no doubt far from definitive looking at only 2540 SNPs and a limited number of populations.
Finns were not included in the analysis, but this independent evidence of west-east gene flow in northern Eurasia is in line with the theory that N3 (Tat C) Y chromosomes diffused from Northeastern Europeans to Siberians rather than the reverse:
'Our technique enables us to identify more subtle details about genetic contributions than other methods,' said Dr Garrett Hellenthal from the Department of Statistics at Oxford, a co-author on the paper. 'By incorporating the inheritance of 'blocks' of DNA between generations, rather than just individual genes, it captures a panoramic view of the sharing of patterns of DNA across the entire human genome. This allows us to consider a vast number of possible colonisation scenarios - not just the ones people have already thought of - and use an algorithm to determine the most likely migration routes.'
The new technique was used to analyse 2540 genetic markers using Single Nucleotide Polymorphism data from 927 individuals of diverse ethnicity whose DNA was collected by the Human Diversity Project.
'Humans like to tell stories and amongst the most captivating is the story of the global spread of modern humans from their original homeland in Africa,' said Dr Daniel Falush of University College Cork, a co-author on the paper. 'Traditionally this has been the preserve of anthropologists but geneticists are now starting to make an important contribution. However, genetic evidence is still typically analysed in the light of anthropological preconceptions; statistical techniques help us to see things more objectively.'
The researchers believe their method can cope with much larger datasets with over 500,000 genetic markers. Further developments of the technique should allow human ancestry to be reconstructed in unprecedented detail and give a perspective independent of anthropological theory and interpretation.
Sounds interesting, but no doubt far from definitive looking at only 2540 SNPs and a limited number of populations.
PLoS Genet 4(5): e1000078. doi:10.1371/journal.pgen.1000078
Inferring Human Colonization History Using a Copying Model
Garrett Hellenthal et al.
Genome-wide scans of genetic variation can potentially provide detailed information on how modern humans colonized the world but require new methods of analysis. We introduce a statistical approach that uses Single Nucleotide Polymorphism (SNP) data to identify sharing of chromosomal segments between populations and uses the pattern of sharing to reconstruct a detailed colonization scenario. We apply our model to the SNP data for the 53 populations of the Human Genome Diversity Project described in Conrad et al. (Nature Genetics 38,1251-60, 2006). Our results are consistent with the consensus view of a single “Out-of-Africa” bottleneck and serial dilution of diversity during global colonization, including a prominent East Asian bottleneck. They also suggest novel details including: (1) the most northerly East Asian population in the sample (Yakut) has received a significant genetic contribution from the ancestors of the most northerly European one (Orcadian). (2) Native South Americans have received ancestry from a source closely related to modern North-East Asians (Mongolians and Oroquen) that is distinct from the sources for native North Americans, implying multiple waves of migration into the Americas. A detailed depiction of the peopling of the world is available in animated form.
[. . .]
Gene Flow from Europe to East Asia around the Arctic Circle
In our inferred scenario there is little gene flow between East Asian and Europeans and the Yakut is the only East Asian population to have two European donors; the Russians and the Orcadians. The Russian contribution is not surprising because the Yakut live in North East Russia. The Orcadian contribution is particularly noteworthy because removing these donors reduces the log-likelihood of generating the Yakut chromosomes by 2.5 times more than removing donors from any other population (Table S2). The Orcadians are also the only other European population to donate to other East Asians, namely the Han from Northern China and the Hezhen, who are also amongst the most Northerly East Asian populations in the sample. On this basis we hypothesize that there has been an episode of gene flow from Europe to East Asia. We tested the robustness of this inference by putting Orcadians last in the ordering. The Yakut replaced the Orcadians with Sardinians, who are a major donor to the Orcadians. The Hezhen and the Han from Northern China did not acquire new European donors, consistent with the gene flow from Europe being less quantitatively important to these two populations than to the more Northerly Yakut. Orcadians did not gain any East Asian donors by being placed last in the ordering, strengthening the inference that the direction of the gene flow was from Europe to East Asia.
Finns were not included in the analysis, but this independent evidence of west-east gene flow in northern Eurasia is in line with the theory that N3 (Tat C) Y chromosomes diffused from Northeastern Europeans to Siberians rather than the reverse:
The peculiar Y chromosomal DNA variant, known as Tat C, is also dominant in almost all the indigenous peoples of Siberia, from the nomadic Yakuts right across to the Chukchis and Siberian Inuits living on the shores of the Bering Strait - regardless of what language they may communicate in.
According to Prof. Villems, the "point" in all this is that among the Finno-Ugric races of Europe this genetic inheritance is much more diverse, more multibranched, and hence apparently older than among any of the Siberian peoples.
Height (ESHG 2008 abstracts)
European Human Genetics Conference (abstract database)
PPARG and PPARGC1A gene variants are associated with height in athletes
I. A. Mozhayskaya, I. I. Ahmetov, V. A. Rogozkin;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.238
PPARgamma nuclear receptor positively promotes adipogenesis and negatively regulates osteoblast differentiation, indicating that PPARgamma is a negative regulator of bone mass. The Ala12 variant of PPARG gene Pro12Ala polymorphism is associated with lower transcriptional activity, increased body mass index and height in humans. PPARGC1A has been identified as a transcriptional coactivator of PPARgamma. Carriers of the Ser482 allele have been reported to have lower levels of PPARGC1A by comparison with Gly482 allele homozygotes. Therefore, one could expect that the Gly482Ser polymorphism might affect height too. The aim of the study was to investigate an association of PPARG Pro12Ala and PPARG1CA Gly482Ser polymorphisms with height in Russian male rowers and speed skaters. The study involved 99 rowers (height - 191.1 (5.4) cm, weight - 86 (9.7) kg; aged 20-27) and 64 speed skaters (height - 179.6 (6) cm, weight - 74.9 (8.8) kg; aged 20-25). Rowers were divided into three groups: the highest group (195-204 cm), the middle group (189-194 cm) and the lowest group (182-188 cm). Gene polymorphisms were determined by PCR-RLFP. We found that the presence of the PPARG 12Ala allele was significantly associated with higher body height (Ala/Ala+Pro/Ala- 182.7 (4.9) cm vs. Pro/Pro - 178.7 (6.1) cm; P=0.023) in speed skaters. The frequency of the PPARG1CA 482Ser allele was significantly higher in the highest group of rowers (33.3%), than in the middle (22.5%) and the lowest (18.8%) groups (P=0.032). In conclusion, functional polymorphisms in PPARG and PPARG1CA genes may influence the growth of the skeleton in male athletes.
Genome-wide association analysis identifies multiple loci associated with normal variation in height
M. N. Weedon1, H. Lango1, G. Lettre2, .. The GIANT Consortium1,2;
1Peninsula Medical School, Exeter, United Kingdom, 2Broad Institute, Boston, MA, United States.
Presentation Number: P07.060
There are many single gene disorders that affect stature, but little is known about the genetic variants that explain normal variation of adult height. The availability of genome-wide association data offers new opportunities to identify the genes involved in normal growth.
Recent meta-analyses of genome-wide association studies (GWAS), using up to 16,000 individuals, have identified 22 independent loci associated with height (p<5x10-8). The GIANT consortium has now extended these analyses, using imputation methods, to combine association results from 13 GWAS, with a total sample size of >32,000 individuals.
Initial meta-analysis identified 111 independent loci with p<1x10-5 and 50 with p<5x10-7. Confirmed loci implicate a wide range of molecular processes involved in normal growth. These include Hedgehog signaling (PTCH1, HHIP, IHH), chromatin remodeling (SCMH1, HMGA2), and basic cell cycling (CDK6, ANAPC13). Some of the variants and genes have been connected to other diseases, including cancer, suggesting that variants associated with height may also influence disease susceptibility. Many of the associated loci include genes known to be involved in growth based on monogenic human studies. Other loci implicate genes previously unsuspected to have a role in growth, and represent excellent candidate genes for, as yet unexplained, growth-related single gene disorders.
Combining data from many genome-wide association studies is likely to result in the identification of hundreds of loci that influence adult height. These data should result in an unprecedented increase in our knowledge of the genetics of growth and development.
A genome-wide scan of adult human stature and skeletal size
Presentation Time: Tuesday, 10:45 a.m. - 11:00 a.m.
N. Soranzo1, F. Rivadeneira2, U. Chinappen3, M. Inouye1, B. J. Richards3, S. Potter1, R. Gwilliam1, K. Papadakis4, E. Wheeler1, I. Barroso1, D. Hart5, G. Livshits6, R. J. F. Loos7, D. Strachan4, N. J. Wareham7, T. D. Spector3, A. Uitterlinden2, P. Deloukas1;
1The Wellcome Trust Sanger Institute, Hinxton, United Kingdom, 2Erasmus MC, Rotterdam, The Netherlands, 3School of Medicine, King’s College London, London, United Kingdom, 4St George's, University of London, London, United Kingdom, 5St. Thomas' Hospital, London, United Kingdom, 6Tel Aviv University, Tel Aviv, Israel, 7Institute of Metabolic Science, Cambridge, United Kingdom.
Presentation Number: C13.1
Human adult stature is a classical quantitative trait and a paradigm for genetic association studies of quantitative trait variation. We have carried out a meta-analysis of four genome-wide association scans of stature produced using the Illumina HumanHap300 SNP panel in 10,050 adults from four population-based cohorts (TwinsUK, EPIC Norfolk and 1958 Birth Cohort from the UK and the Rotterdam Study from the Netherlands). We have identified eighteen loci showing association with height with P-values of less than 10-5, which we have brought forward for replication in an independent sample of 9,000 individuals.
The signals identified provide strong evidence for replication in genomic regions previously implicated in height, including HMGA2 (rs8756, P-value = 5x10-13) and GDF5-UQCC (rs4911494, P-value = 1.5x10-10). In addition, we have identified novel candidate genetic loci for human height, some of which are in or near genes implicated in cellular growth and development (HHIP, ADAMTSL3 and DLEU7). In an attempt to dissect the mechanisms underlying human growth, we have tested the association of these novel candidate height loci with different measurements of skeletal growth. Our results provide both novel and confirmatory evidence for the implication of genes and pathways in human growth, thus contributing to the understanding of the biological processes underlying many common and severe human diseases.
Genome wide association analysis in human height of European-originated monozygotic female twins
J. A. Kettunen1,2, I. Lindqvist2, S. Ripatti2,3, T. D. Spector4, N. G. Martin5, L. Peltonen1,2, M. Perola2;
1Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 2National Public Health Institute, Helsinki, Finland, 3Karolinska Institutet, Stockholm, Sweden, 4Twin Research and Genetic Epidemiology Unit, King's College, London, United Kingdom, 5Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Austria.
Presentation Number: P06.126
Stature (i.e. adult height) is a quantitative trait with high heritability. Various interesting regions in the human genome have been linked to adult stature but only few have been confirmed by later studies. Two genome wide association (GWA) studies have been published recently and they identified two loci (HMGA2 and GDF5-UQCC) to be strongly associated to stature after extensive replication studies. In this study we report a genome wide association analysis performed on 1631 European monozygotic female twin pairs from the GenomEUtwin consortium. One of each pair was genotyped with the Illumina HumanHap300-duo chip. Whole genome association analysis was performed with the PLINK-program. Area of residence and age were used as covariates in all of the analyses. Our study had two goals: We wanted to reduce the environmental variance by using the mean of each pair as a phenotype. We observed an association (p = 3.14*10-6) on 8q24 locus underlying the linkage peak identified previously in our linkage scan on European dizygotic twins (LOD 3.28). The replication study is underway for the most significant findings in this GWA scan. Second, we analyzed whether we could pinpoint any regions in genome which would be associated to the difference within each pair. This approach was aiming to find genes responsible for increasing variance in human height, thus potentially indicating for example GxE interaction or imprinting/gene silencing. The most significant finding for variance in stature (p = 1.22 * 10-5) was identified on 6q14 region.
Genetic analysis of adult stature in Dutch isolated population
I. V. Zorkoltseva1, T. I. Axenovich1, C. M. van Duijn2;
1Institute of Cytology and Genetics, Novosibirsk, Russian Federation, 2Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, Netherlands.
Presentation Number: P06.008
We analysed a large complex pedigree from a Dutch genetically isolated population. About 2600 of 19700 pedigree members were phenotyped and genotyped for autosomal 5208 SNPs (Illumina 6K linkage panel). Complex segregation analysis of adult height was performed under mixed model including effects of biallelic major gene, polygene, age and sex. We used likelihood approximation based on breaking pedigree loops. The results confirmed large contribution of genes in the trait variance (h2 = 0.85 ) and significance of major gene effect in accordance with Elston-Stewart test. Three genotypic means were estimated as 183.5, 178.3 and 174.6 cm in males at 40 years with average difference of male and female genotypic means about 13 cm. The putative major gene explained 18% of trait variance.
A genome-wide scan was performed by variance-components method using Merlin program. Prior to analysis, the pedigree was split into smaller non-overlapping fragments, with maximum bit-size of 18. No loci demonstrated significant linkage, however for 6 loci linkage was suggestive:
SNP Chr Position(cM) LodScore
rs1993104 19 56.9 2.71
rs1873191 18 44.7 2.60
rs1019845 2 195.8 2.27
rs958883 5 123.3 2.15
rs936347 16 17.2 2.11
rs216223 17 2.1 2.11
Of these six loci, five were identified in previous linkage analyses, while locus at chromosome 16 (rs936347) was new.
PPARG and PPARGC1A gene variants are associated with height in athletes
I. A. Mozhayskaya, I. I. Ahmetov, V. A. Rogozkin;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.238
PPARgamma nuclear receptor positively promotes adipogenesis and negatively regulates osteoblast differentiation, indicating that PPARgamma is a negative regulator of bone mass. The Ala12 variant of PPARG gene Pro12Ala polymorphism is associated with lower transcriptional activity, increased body mass index and height in humans. PPARGC1A has been identified as a transcriptional coactivator of PPARgamma. Carriers of the Ser482 allele have been reported to have lower levels of PPARGC1A by comparison with Gly482 allele homozygotes. Therefore, one could expect that the Gly482Ser polymorphism might affect height too. The aim of the study was to investigate an association of PPARG Pro12Ala and PPARG1CA Gly482Ser polymorphisms with height in Russian male rowers and speed skaters. The study involved 99 rowers (height - 191.1 (5.4) cm, weight - 86 (9.7) kg; aged 20-27) and 64 speed skaters (height - 179.6 (6) cm, weight - 74.9 (8.8) kg; aged 20-25). Rowers were divided into three groups: the highest group (195-204 cm), the middle group (189-194 cm) and the lowest group (182-188 cm). Gene polymorphisms were determined by PCR-RLFP. We found that the presence of the PPARG 12Ala allele was significantly associated with higher body height (Ala/Ala+Pro/Ala- 182.7 (4.9) cm vs. Pro/Pro - 178.7 (6.1) cm; P=0.023) in speed skaters. The frequency of the PPARG1CA 482Ser allele was significantly higher in the highest group of rowers (33.3%), than in the middle (22.5%) and the lowest (18.8%) groups (P=0.032). In conclusion, functional polymorphisms in PPARG and PPARG1CA genes may influence the growth of the skeleton in male athletes.
Genome-wide association analysis identifies multiple loci associated with normal variation in height
M. N. Weedon1, H. Lango1, G. Lettre2, .. The GIANT Consortium1,2;
1Peninsula Medical School, Exeter, United Kingdom, 2Broad Institute, Boston, MA, United States.
Presentation Number: P07.060
There are many single gene disorders that affect stature, but little is known about the genetic variants that explain normal variation of adult height. The availability of genome-wide association data offers new opportunities to identify the genes involved in normal growth.
Recent meta-analyses of genome-wide association studies (GWAS), using up to 16,000 individuals, have identified 22 independent loci associated with height (p<5x10-8). The GIANT consortium has now extended these analyses, using imputation methods, to combine association results from 13 GWAS, with a total sample size of >32,000 individuals.
Initial meta-analysis identified 111 independent loci with p<1x10-5 and 50 with p<5x10-7. Confirmed loci implicate a wide range of molecular processes involved in normal growth. These include Hedgehog signaling (PTCH1, HHIP, IHH), chromatin remodeling (SCMH1, HMGA2), and basic cell cycling (CDK6, ANAPC13). Some of the variants and genes have been connected to other diseases, including cancer, suggesting that variants associated with height may also influence disease susceptibility. Many of the associated loci include genes known to be involved in growth based on monogenic human studies. Other loci implicate genes previously unsuspected to have a role in growth, and represent excellent candidate genes for, as yet unexplained, growth-related single gene disorders.
Combining data from many genome-wide association studies is likely to result in the identification of hundreds of loci that influence adult height. These data should result in an unprecedented increase in our knowledge of the genetics of growth and development.
A genome-wide scan of adult human stature and skeletal size
Presentation Time: Tuesday, 10:45 a.m. - 11:00 a.m.
N. Soranzo1, F. Rivadeneira2, U. Chinappen3, M. Inouye1, B. J. Richards3, S. Potter1, R. Gwilliam1, K. Papadakis4, E. Wheeler1, I. Barroso1, D. Hart5, G. Livshits6, R. J. F. Loos7, D. Strachan4, N. J. Wareham7, T. D. Spector3, A. Uitterlinden2, P. Deloukas1;
1The Wellcome Trust Sanger Institute, Hinxton, United Kingdom, 2Erasmus MC, Rotterdam, The Netherlands, 3School of Medicine, King’s College London, London, United Kingdom, 4St George's, University of London, London, United Kingdom, 5St. Thomas' Hospital, London, United Kingdom, 6Tel Aviv University, Tel Aviv, Israel, 7Institute of Metabolic Science, Cambridge, United Kingdom.
Presentation Number: C13.1
Human adult stature is a classical quantitative trait and a paradigm for genetic association studies of quantitative trait variation. We have carried out a meta-analysis of four genome-wide association scans of stature produced using the Illumina HumanHap300 SNP panel in 10,050 adults from four population-based cohorts (TwinsUK, EPIC Norfolk and 1958 Birth Cohort from the UK and the Rotterdam Study from the Netherlands). We have identified eighteen loci showing association with height with P-values of less than 10-5, which we have brought forward for replication in an independent sample of 9,000 individuals.
The signals identified provide strong evidence for replication in genomic regions previously implicated in height, including HMGA2 (rs8756, P-value = 5x10-13) and GDF5-UQCC (rs4911494, P-value = 1.5x10-10). In addition, we have identified novel candidate genetic loci for human height, some of which are in or near genes implicated in cellular growth and development (HHIP, ADAMTSL3 and DLEU7). In an attempt to dissect the mechanisms underlying human growth, we have tested the association of these novel candidate height loci with different measurements of skeletal growth. Our results provide both novel and confirmatory evidence for the implication of genes and pathways in human growth, thus contributing to the understanding of the biological processes underlying many common and severe human diseases.
Genome wide association analysis in human height of European-originated monozygotic female twins
J. A. Kettunen1,2, I. Lindqvist2, S. Ripatti2,3, T. D. Spector4, N. G. Martin5, L. Peltonen1,2, M. Perola2;
1Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 2National Public Health Institute, Helsinki, Finland, 3Karolinska Institutet, Stockholm, Sweden, 4Twin Research and Genetic Epidemiology Unit, King's College, London, United Kingdom, 5Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Austria.
Presentation Number: P06.126
Stature (i.e. adult height) is a quantitative trait with high heritability. Various interesting regions in the human genome have been linked to adult stature but only few have been confirmed by later studies. Two genome wide association (GWA) studies have been published recently and they identified two loci (HMGA2 and GDF5-UQCC) to be strongly associated to stature after extensive replication studies. In this study we report a genome wide association analysis performed on 1631 European monozygotic female twin pairs from the GenomEUtwin consortium. One of each pair was genotyped with the Illumina HumanHap300-duo chip. Whole genome association analysis was performed with the PLINK-program. Area of residence and age were used as covariates in all of the analyses. Our study had two goals: We wanted to reduce the environmental variance by using the mean of each pair as a phenotype. We observed an association (p = 3.14*10-6) on 8q24 locus underlying the linkage peak identified previously in our linkage scan on European dizygotic twins (LOD 3.28). The replication study is underway for the most significant findings in this GWA scan. Second, we analyzed whether we could pinpoint any regions in genome which would be associated to the difference within each pair. This approach was aiming to find genes responsible for increasing variance in human height, thus potentially indicating for example GxE interaction or imprinting/gene silencing. The most significant finding for variance in stature (p = 1.22 * 10-5) was identified on 6q14 region.
Genetic analysis of adult stature in Dutch isolated population
I. V. Zorkoltseva1, T. I. Axenovich1, C. M. van Duijn2;
1Institute of Cytology and Genetics, Novosibirsk, Russian Federation, 2Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, Netherlands.
Presentation Number: P06.008
We analysed a large complex pedigree from a Dutch genetically isolated population. About 2600 of 19700 pedigree members were phenotyped and genotyped for autosomal 5208 SNPs (Illumina 6K linkage panel). Complex segregation analysis of adult height was performed under mixed model including effects of biallelic major gene, polygene, age and sex. We used likelihood approximation based on breaking pedigree loops. The results confirmed large contribution of genes in the trait variance (h2 = 0.85 ) and significance of major gene effect in accordance with Elston-Stewart test. Three genotypic means were estimated as 183.5, 178.3 and 174.6 cm in males at 40 years with average difference of male and female genotypic means about 13 cm. The putative major gene explained 18% of trait variance.
A genome-wide scan was performed by variance-components method using Merlin program. Prior to analysis, the pedigree was split into smaller non-overlapping fragments, with maximum bit-size of 18. No loci demonstrated significant linkage, however for 6 loci linkage was suggestive:
SNP Chr Position(cM) LodScore
rs1993104 19 56.9 2.71
rs1873191 18 44.7 2.60
rs1019845 2 195.8 2.27
rs958883 5 123.3 2.15
rs936347 16 17.2 2.11
rs216223 17 2.1 2.11
Of these six loci, five were identified in previous linkage analyses, while locus at chromosome 16 (rs936347) was new.
2008-05-26 links
Statistical Modeling, Causal Inference, and Social Science: Voting patterns of Jews and other religious groups; Quarterbacks and psychometrics
Studium generale: Die Hausmaus in der Weltgeschichte
Mathilda's Anthropology Blog: The domestication and ancient pedigree of the housecat
Plomin et al.: Testing replication of a 5-SNP set for general cognitive ability in six population samples
mtDNA and disease: no association between the common [mitochondrial DNA haplogroups] and prostate cancer in the Korean population
AJPA: Middle Eastern and European mtDNA lineages characterize populations from eastern Crete
Studium generale: Die Hausmaus in der Weltgeschichte
Mathilda's Anthropology Blog: The domestication and ancient pedigree of the housecat
Plomin et al.: Testing replication of a 5-SNP set for general cognitive ability in six population samples
mtDNA and disease: no association between the common [mitochondrial DNA haplogroups] and prostate cancer in the Korean population
AJPA: Middle Eastern and European mtDNA lineages characterize populations from eastern Crete
Positive selection at MC1R in Europeans?
BMC Genetics 2008, 9:31doi:10.1186/1471-2156-9-31
Nucleotide diversity and population differentiation of the Melanocortin 1 Receptor gene, MC1R
Sharon A Savage et al.
Background
The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk.
Results
Allele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, ?, was much higher (10.1 × 10-4) than in other genes for all subjects. A large degree of population differentiation, determined by FST, was also present, particularly between Asia and all other populations, due to the p.R163Q (c.488 G>A) polymorphism. The least amount of differentiation was between the United States, Northern Europe, and Southern Europe. Tajima's D statistic suggested the presence of positive selection in individuals from Europe.
Conclusion
This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.
[. . .]
Numerous studies have demonstrated associations between specific MC1R variants and red hair, light skin, poor tanning ability and heavy freckling [4-9]. A recent genome-wide association scan confirmed the role of MC1R SNPs in hair, eye, and skin pigmentation[3]. The functional role of many of these variants has been described [10-13]. Several MC1R variants are also associated with increased risk of malignant melanoma in a variety of populations [14-22] The effect of MC1R polymorphisms in melanoma risk appears to extend beyond its effect on pigmentation in most of these investigations, and to be linked to melanomas harboring mutations in the BRAF oncogene[23].
Several hypotheses have been generated in an effort to understand the evolutionary history of skin pigmentation in humans. It has been suggested that as humans migrated out of Africa to climates with more limited exposure to sunlight, relaxation of functional constraints in pigmentation genes, including MC1R, or selection for functionally relevant variants that led to lighter skin pigmentation occurred[24]. This could result in an improved ability to synthesize vitamin D in the presence of limited sunlight exposures [25-27]. It has also been suggested that darker skin is favored in regions closer to the equator for protection against ultraviolet radiation[24]. In addition, differences in skin pigmentation could protect against pathogens and cold injury, and may have also been important in sexual selection[28].
[. . . ]
Several studies have evaluated genetic adaptation of the MC1R gene for evidence of positive selection with conflicting results. Some studies suggested that purifying selection is present in Africa and that relaxation of functional constraint in non-African populations, instead of positive selection, is present[25,27,40]. On the other hand, most recent studies have found evidence of positive selection at other pigmentation genes. For example, Myles et al [2] found evidence for positive selection in the DCT gene among individuals of Chinese ancestry. In their study, MC1R interpretations were limited because of the different SNPs genotyped between the Perlegen and HapMap data sets studied. In a study of 118 putative skin pigmentation genes, data were consistent with positive selection in subjects from Europe (OCA2, TYRP1, and KITLG) and in Asians (DCT, EGFR, and DRD2)[38]. Unfortunately, MC1R could not be evaluated in that study due to ascertainment criteria. It was also suggested that at least weak, recent positive selection may be present in MC1R, based on the AF variability between CEPH Utah and East Asian HapMap samples[3]. Our data suggest that MC1R may be under positive selection in some populations, although additional studies are needed to further evaluate this finding.
Nucleotide diversity and population differentiation of the Melanocortin 1 Receptor gene, MC1R
Sharon A Savage et al.
Background
The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk.
Results
Allele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, ?, was much higher (10.1 × 10-4) than in other genes for all subjects. A large degree of population differentiation, determined by FST, was also present, particularly between Asia and all other populations, due to the p.R163Q (c.488 G>A) polymorphism. The least amount of differentiation was between the United States, Northern Europe, and Southern Europe. Tajima's D statistic suggested the presence of positive selection in individuals from Europe.
Conclusion
This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.
[. . .]
Numerous studies have demonstrated associations between specific MC1R variants and red hair, light skin, poor tanning ability and heavy freckling [4-9]. A recent genome-wide association scan confirmed the role of MC1R SNPs in hair, eye, and skin pigmentation[3]. The functional role of many of these variants has been described [10-13]. Several MC1R variants are also associated with increased risk of malignant melanoma in a variety of populations [14-22] The effect of MC1R polymorphisms in melanoma risk appears to extend beyond its effect on pigmentation in most of these investigations, and to be linked to melanomas harboring mutations in the BRAF oncogene[23].
Several hypotheses have been generated in an effort to understand the evolutionary history of skin pigmentation in humans. It has been suggested that as humans migrated out of Africa to climates with more limited exposure to sunlight, relaxation of functional constraints in pigmentation genes, including MC1R, or selection for functionally relevant variants that led to lighter skin pigmentation occurred[24]. This could result in an improved ability to synthesize vitamin D in the presence of limited sunlight exposures [25-27]. It has also been suggested that darker skin is favored in regions closer to the equator for protection against ultraviolet radiation[24]. In addition, differences in skin pigmentation could protect against pathogens and cold injury, and may have also been important in sexual selection[28].
[. . . ]
Several studies have evaluated genetic adaptation of the MC1R gene for evidence of positive selection with conflicting results. Some studies suggested that purifying selection is present in Africa and that relaxation of functional constraint in non-African populations, instead of positive selection, is present[25,27,40]. On the other hand, most recent studies have found evidence of positive selection at other pigmentation genes. For example, Myles et al [2] found evidence for positive selection in the DCT gene among individuals of Chinese ancestry. In their study, MC1R interpretations were limited because of the different SNPs genotyped between the Perlegen and HapMap data sets studied. In a study of 118 putative skin pigmentation genes, data were consistent with positive selection in subjects from Europe (OCA2, TYRP1, and KITLG) and in Asians (DCT, EGFR, and DRD2)[38]. Unfortunately, MC1R could not be evaluated in that study due to ascertainment criteria. It was also suggested that at least weak, recent positive selection may be present in MC1R, based on the AF variability between CEPH Utah and East Asian HapMap samples[3]. Our data suggest that MC1R may be under positive selection in some populations, although additional studies are needed to further evaluate this finding.
Longevity (ESHG 2008 abstracts)
European Human Genetics Conference (abstract database)
The relation of common diseases SNPs and life span: no evidence for shared genetic component
O. Y. Byichkova1, O. A. Makeeva1, I. V. Tsimbal'uk2, K. V. Puzyrev3, V. N. Maksimov4, V. P. Puzyrev1,2;
1Research Institute of Medical Genetics, Tomsk, Russian Federation, 2Siberian State Medical University, Tomsk, Russian Federation, 3Research Institute of Cardiology, Tomsk, Russian Federation, 4Research Institute of Therapy, Novosibirsk, Russian Federation.
Presentation Number: P07.028
Life span is a multifactorial trait with a strong genetic component. Besides the number of genes has been directly implicated into the processes of ageing and longevity, the genes responsible for common diseases such as cardiovascular (CVD) or immunity disorders are also had to be under intent consideration. The persistence and both elimination from human populations ‘predisposing’ common genetic variants is forced by a complex interplay of different evolutionary processes; some variants being unfavorable during particular periods of life can offer their owners advantages on the others. Latter should be taken into account e.g. while developing genetic test and interpreting frequently discrepant genetic data on disease association. Testing the hypothesis that CVD predisposing alleles can be related to the life span, we investigate several cohorts: healthy controls of childbearing age (aged from 20 to 45, n=282), nonagenarians (aged 90 and over, n=235) and patients with cardiovascular disease (arterial hypertension with different complications) (n=231) from the same geographic region and ethnicity (East Siberia, Russians) and genotyped for several well-known CVD candidate genes polymorphisms (G-308A TNF, C894T NOS3, and A1166C AGTR1). While all the three SNPs under study affected several important cardiovascular endophenotypes (arterial blood pressure measurements, cardiac parameters, left ventricular hypertrophy development est.) no significant differences had been revealed among nonagenarians and middle aged group. In this study we never found actual proof for the stated hypothesis, though a huge amount of other genetic variants and the larger samples are needed to be tested before its decline.
Age-dependent genetic polymorphism frequencies and Gene - Pass
V. S. Baranov1, H. V. Baranova2, O. S. Glotov1;
1Ott’s Institute of Obstetrics & Gynecology, St.Petersburg, Russian Federation, 2European Institute of Personalized Prevention, Nice, France.
Presentation Number: P07.058
The report highlights the results of collaborative studies of personalized anti-aging medicine and its impact into longevity and aging. Special attention is paid to the gene nets of cardiovascular diseases, renin-angiotensin system, diabetus mellitus, osteoporosis etc. Polymorphic variants of at least some particular genes such as ACE, AGT, PAII, MTHFR, APOE, also as metabolic genes, like GSTs and other oxidative stress markers (NOS) are considered as the most plausible candidates of the genes crucial for aging. Molecular analysis of these particular genes supplemented with relevant metabolic genes testing, responsible for efficiency of detoxification system might have substantial contribution into personalyzed anti - aging medicine. The data on allele frequencies distribution for 10 differenet genes in newborns (106), 119 middle age and 148 old people over 69 are presented Relevant gene testing supplemented with its adequate sophisticated interpretation and constructive recommendations might have substantial contribution to human health and should be considered as a new highly promising tool in anti-aging medicine “Gene - pass ” term is suggested for the individual DNA data bank reflecting increased personal susceptibility to these common disorders. Tremendous impact to its practical application could be achieved through wide scale application of biochip technology. The latter are already available or are in progress for a number of multifactorial diseases. Special attention is paid to Genetic Pass of Reproductive Health - a version of Genetic Pass adjusted to the needs of pregnant woman. Life in harmony with personal gene makeup remains indispensable prerequisite of longevity and good health..
Study on a possible effect of four longevity candidate genes (ACE, PON1, PPAR-gamma, APOE) on human fertility
R. M. Corbo1,2, L. Ulizzi1, L. Piombo1, R. Scacchi2;
1La Sapienza University, Rome, Italy, 2CNR Institute of Molecular Biology and Pathology, Rome, Italy.
Presentation Number: P07.080
A possible effect on fertility of four genes [angiotensin 1-converting enzyme (ACE), paraoxonase (PON1), peroxisome proliferator-activated receptor gamma (PPAR-g), and apolipoprotein E(APOE)] previously found associated with longevity was sought in order to determine whether they have a pleiotropic action at different life ages. The study population was 151 Italian subjects whose reproductive life took place at the beginning of the demographic transition (declining fertility and longer life expectancy) and who had produced a mean number of children (3.6±2.3) such as to be still useful to detect a differential reproductive efficiency associated with different genotypes.
Of these four longevity candidate genes, only PPAR-g and APOE appeared to have an effect on fertility, indicating their possible influence on reproductive efficiency. The PPAR-g Pro/Ala genotype, which in a previous study (Barbieri et el. 2004) showed a positive association with longevity only in men, was found associated with a higher number of children (6.1 ± 3.3) than Pro/Pro genotype (3.3 ± 1.9, p=0.001) only in men. Compared with the other APOE alleles, the APOE*2 allele, considered as an allele favouring a longer life-span, was confirmed to be associated with the lowest fertility (p=0.03). The logistic regression analysis indicated that APOE and PPAR-g polymorphisms act as independent determinants of reproductive efficiency. These data suggest that the APOE*2 allele may follow the model of antagonist pleiotropy, whereas the PPAR-g Pro/Ala genotype seems to exert beneficial effects both early in life and in advanced age in a gender-specific way.
The relation of common diseases SNPs and life span: no evidence for shared genetic component
O. Y. Byichkova1, O. A. Makeeva1, I. V. Tsimbal'uk2, K. V. Puzyrev3, V. N. Maksimov4, V. P. Puzyrev1,2;
1Research Institute of Medical Genetics, Tomsk, Russian Federation, 2Siberian State Medical University, Tomsk, Russian Federation, 3Research Institute of Cardiology, Tomsk, Russian Federation, 4Research Institute of Therapy, Novosibirsk, Russian Federation.
Presentation Number: P07.028
Life span is a multifactorial trait with a strong genetic component. Besides the number of genes has been directly implicated into the processes of ageing and longevity, the genes responsible for common diseases such as cardiovascular (CVD) or immunity disorders are also had to be under intent consideration. The persistence and both elimination from human populations ‘predisposing’ common genetic variants is forced by a complex interplay of different evolutionary processes; some variants being unfavorable during particular periods of life can offer their owners advantages on the others. Latter should be taken into account e.g. while developing genetic test and interpreting frequently discrepant genetic data on disease association. Testing the hypothesis that CVD predisposing alleles can be related to the life span, we investigate several cohorts: healthy controls of childbearing age (aged from 20 to 45, n=282), nonagenarians (aged 90 and over, n=235) and patients with cardiovascular disease (arterial hypertension with different complications) (n=231) from the same geographic region and ethnicity (East Siberia, Russians) and genotyped for several well-known CVD candidate genes polymorphisms (G-308A TNF, C894T NOS3, and A1166C AGTR1). While all the three SNPs under study affected several important cardiovascular endophenotypes (arterial blood pressure measurements, cardiac parameters, left ventricular hypertrophy development est.) no significant differences had been revealed among nonagenarians and middle aged group. In this study we never found actual proof for the stated hypothesis, though a huge amount of other genetic variants and the larger samples are needed to be tested before its decline.
Age-dependent genetic polymorphism frequencies and Gene - Pass
V. S. Baranov1, H. V. Baranova2, O. S. Glotov1;
1Ott’s Institute of Obstetrics & Gynecology, St.Petersburg, Russian Federation, 2European Institute of Personalized Prevention, Nice, France.
Presentation Number: P07.058
The report highlights the results of collaborative studies of personalized anti-aging medicine and its impact into longevity and aging. Special attention is paid to the gene nets of cardiovascular diseases, renin-angiotensin system, diabetus mellitus, osteoporosis etc. Polymorphic variants of at least some particular genes such as ACE, AGT, PAII, MTHFR, APOE, also as metabolic genes, like GSTs and other oxidative stress markers (NOS) are considered as the most plausible candidates of the genes crucial for aging. Molecular analysis of these particular genes supplemented with relevant metabolic genes testing, responsible for efficiency of detoxification system might have substantial contribution into personalyzed anti - aging medicine. The data on allele frequencies distribution for 10 differenet genes in newborns (106), 119 middle age and 148 old people over 69 are presented Relevant gene testing supplemented with its adequate sophisticated interpretation and constructive recommendations might have substantial contribution to human health and should be considered as a new highly promising tool in anti-aging medicine “Gene - pass ” term is suggested for the individual DNA data bank reflecting increased personal susceptibility to these common disorders. Tremendous impact to its practical application could be achieved through wide scale application of biochip technology. The latter are already available or are in progress for a number of multifactorial diseases. Special attention is paid to Genetic Pass of Reproductive Health - a version of Genetic Pass adjusted to the needs of pregnant woman. Life in harmony with personal gene makeup remains indispensable prerequisite of longevity and good health..
Study on a possible effect of four longevity candidate genes (ACE, PON1, PPAR-gamma, APOE) on human fertility
R. M. Corbo1,2, L. Ulizzi1, L. Piombo1, R. Scacchi2;
1La Sapienza University, Rome, Italy, 2CNR Institute of Molecular Biology and Pathology, Rome, Italy.
Presentation Number: P07.080
A possible effect on fertility of four genes [angiotensin 1-converting enzyme (ACE), paraoxonase (PON1), peroxisome proliferator-activated receptor gamma (PPAR-g), and apolipoprotein E(APOE)] previously found associated with longevity was sought in order to determine whether they have a pleiotropic action at different life ages. The study population was 151 Italian subjects whose reproductive life took place at the beginning of the demographic transition (declining fertility and longer life expectancy) and who had produced a mean number of children (3.6±2.3) such as to be still useful to detect a differential reproductive efficiency associated with different genotypes.
Of these four longevity candidate genes, only PPAR-g and APOE appeared to have an effect on fertility, indicating their possible influence on reproductive efficiency. The PPAR-g Pro/Ala genotype, which in a previous study (Barbieri et el. 2004) showed a positive association with longevity only in men, was found associated with a higher number of children (6.1 ± 3.3) than Pro/Pro genotype (3.3 ± 1.9, p=0.001) only in men. Compared with the other APOE alleles, the APOE*2 allele, considered as an allele favouring a longer life-span, was confirmed to be associated with the lowest fertility (p=0.03). The logistic regression analysis indicated that APOE and PPAR-g polymorphisms act as independent determinants of reproductive efficiency. These data suggest that the APOE*2 allele may follow the model of antagonist pleiotropy, whereas the PPAR-g Pro/Ala genotype seems to exert beneficial effects both early in life and in advanced age in a gender-specific way.
A Saami admixture estimate
As always, I tend to be skeptical about the utility of HLA for accurately determining population affinities.
European Journal of Human Genetics advance online publication 14 May 2008; doi: 10.1038/ejhg.2008.88
Genetic origin of the Swedish Sami inferred from HLA class I and class II allele frequencies
Åsa Johansson et al.
Sami of northern Scandinavia are genetic outliers among European populations and their origin has been difficult to determine. In order to study the genetic origin of the Swedish Sami, we have performed high-resolution typing of the class I HLA-A and -B loci and the class II DRB1, DQB1 and DQA1 loci in the northern and southern Swedish Sami. Several of the common class I alleles in Sami (B*0702, B*1501, B*4002 and A*0301) are found at high frequency in other European populations. However, a number of class I and class II alleles (B*4001, A*2402, DRB1*0901 and DRB1*1101) in the Swedish Sami are characteristic of Asian populations. Admixture analyses indicate that 87% of the Sami gene pool is of European origin and that the Asian contribution is 13%. Our HLA analyses indicate a higher proportion of Asian ancestry in the Sami than shown by previous genetic studies.
Keywords: Sami, HLA, genetic origin, admixture
Structural variation (ESHG 2008 abstracts)
European Human Genetics Conference (abstract database)
Genomic structural variation profiles of world human populations
Presentation Time: Saturday, 7:30 p.m. - 7:45 p.m.
L. Bassaganyas1,2,3, M. Garcia1,3, M. Montfort1,4,3, L. Armengol1,3, X. Estivill1,4,3;
1Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain, 2Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain, 3Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, Catalonia, Spain, 4National Genotyping Center (CeGen), Barcelona, Catalonia, Spain.
Presentation Number: PL2.5
Genomic variants can contribute to genetic disease, and are potential substrates for natural selection resulting in phenotypic differences between individuals. The use of genome-wide molecular methods have revealed the existence of Copy Number Variants (CNVs), genomic segments ranging in size from one kb to several megabases, that are present at variable copy number in comparison with a reference genome. The aim of our study was to determine the existence of population-specific genomic structural variation and to identify genes located in these regions that might contribute to phenotypic differences as well as to differential susceptibility to common disease and environmental exposures of human populations. We have selected 343 individuals from 11 populations from the HGDP-CEPH panel (Biaka- Mbuti Pygmy, Bantu, Mozabite, Bedouin, Brahui, Hazara, Yakut, Papuan-Melanesian, French, Pima and Maya) and 134 individuals from the three populations of the HapMap collection (YRI, CHB and CEU). To detect structural variation we have used array-CGH (Agilent 244K) and array-based comparative genome intensity (Illumina). We have observed differences between populations in 179 loci. 122 of these were already described in the Database of Genomic Variants and 58 coincide with segmental duplications. Interestingly, a number of genes involved in different common disorders or to have phenotypic differences between population groups were found to be variable in copy number among human populations (i.e. RHD, CFHR1, CFHR3 and PRSS1). These loci and others could explain differences in disease predisposition among individuals from different populations and could provide important clues on the adaptation of humans to different environments.
A full survey of common copy number variation in the human genome
Presentation Time: Tuesday, 11:15 a.m. - 11:30 a.m.
R. Redon1, D. F. Conrad1, L. Feuk2, C. Lee3, S. W. Scherer2, M. E. Hurles1, N. P. Carter1;
1Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 2The Hospital for Sick Children, Toronto, ON, Canada, 3Brigham and Women’s Hospital, Boston, MA, United States.
Presentation Number: C13.3
Copy number variation (CNV) in the genome is extensive and yet is grossly under-ascertained. As smaller CNVs are expected to be far more numerous than larger CNVs, improved CNV detection resolution will dramatically increase the numbers of known CNVs. The Genome Structural Variation Consortium has performed comparative genome hybridisation on a genome-wide set of tiling oligonucleotide arrays to discover the majority of common copy number variants >500bp in size in two populations with African and European ancestry. This set covers the assayable portion of the human genome with 42,000,000 probes with a median spacing of ~50bp. In addition we have generated data on a single chimpanzee to provide information on the ancestral state of observed variants. The results reveal, as expected, that previous surveys captured only 5-10% of the CNVs within a single genome. Because the boundaries of thousands of CNVs are defined precisely by this probe set, we can identify accurately functional sequences included in copy number variable regions. This provides new insights into the mechanisms generating chromosomal rearrangements and the biological functions of common CNVs.
A high-resolution structural variation map of a human genome by next-generation, high-throughput paired-end sequencing
Presentation Time: Sunday, 3:15 p.m. - 3:30 p.m.
F. M. De La Vega1, H. E. Peckham2, S. S. Ranade2, S. F. McLaughlin2, C. C. Lee2, Y. Fu2, Z. Zhang1, F. C. L. Hyland1, C. L. Clouser2, A. A. Antipova2, J. M. Manning2, C. L. Hendrickson2, L. Zhang2, E. T. Dimalanta2, T. D. Sokolsky2, M. W. Laptewicz2, B. E. Coleman2, J. K. Ichikawa2, J. B. Warner2, B. Li1, J. M. Kidd3, J. A. Malek4, G. L. Costa2, E. E. Eichler3, K. J. McKernan2;
1Applied Biosystems, Foster City, CA, United States, 2Applied Biosystems, Beverly, MA, United States, 3HHMI, University of Washington, Seattle, WA, United States, 4Weill Cornell Medical College in Qatar, Doha, Qatar.
Presentation Number: C05.2
The human genome and HapMap projects have considerably increased our understanding of the role of sequence variation in evolution and disease. Hybridization microarrays and fosmid-end sequencing reveal that structural variants (SVs) including insertions, deletions, duplications, inversions and translocations are common and extensive. Microarray methods, however, lack resolution and are blind to unbalanced events, while clone-based end-sequencing is time consuming and expensive. Here, we present a high-resolution survey of SVs of a human genome, a HapMap Yoruba sample (NA18507), by ultra-high throughput sequencing of paired-end libraries with the AB SOLiD(TM) System. We sequenced a variety of 2x25-bp paired-end libraries (>15Gb) with insert sizes ranging from 600bp to 6kb (SD 10-23%). Each library provides over 10x physical (clone) coverage, with a total combined physical coverage >60x for 90% of the genome. The high physical coverage and diverse insert sizes allowed detecting small indels within tags (1-10 bp), and approximately 70,000 indels of length 20 bp to >100 kb. Additionally, we sequenced 7Gb of 50-bp fragment libraries, which combined with the paired libraries provided over 12x sequence coverage, allowing us to discover millions of SNPs of which 75% are found in dbSNP. Inferred SVs were compared to a database of end-sequence pairs of 10x physical coverage obtained by di-deoxy sequencing of 40kb fosmid ends. A subset of novel SVs were validated by PCR and Sanger sequencing. Our results serves as a model for further high-resolution exploration of genetic variation in human populations and cancer with next-generation sequencing.
Genomic structural variation profiles of world human populations
Presentation Time: Saturday, 7:30 p.m. - 7:45 p.m.
L. Bassaganyas1,2,3, M. Garcia1,3, M. Montfort1,4,3, L. Armengol1,3, X. Estivill1,4,3;
1Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain, 2Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain, 3Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, Catalonia, Spain, 4National Genotyping Center (CeGen), Barcelona, Catalonia, Spain.
Presentation Number: PL2.5
Genomic variants can contribute to genetic disease, and are potential substrates for natural selection resulting in phenotypic differences between individuals. The use of genome-wide molecular methods have revealed the existence of Copy Number Variants (CNVs), genomic segments ranging in size from one kb to several megabases, that are present at variable copy number in comparison with a reference genome. The aim of our study was to determine the existence of population-specific genomic structural variation and to identify genes located in these regions that might contribute to phenotypic differences as well as to differential susceptibility to common disease and environmental exposures of human populations. We have selected 343 individuals from 11 populations from the HGDP-CEPH panel (Biaka- Mbuti Pygmy, Bantu, Mozabite, Bedouin, Brahui, Hazara, Yakut, Papuan-Melanesian, French, Pima and Maya) and 134 individuals from the three populations of the HapMap collection (YRI, CHB and CEU). To detect structural variation we have used array-CGH (Agilent 244K) and array-based comparative genome intensity (Illumina). We have observed differences between populations in 179 loci. 122 of these were already described in the Database of Genomic Variants and 58 coincide with segmental duplications. Interestingly, a number of genes involved in different common disorders or to have phenotypic differences between population groups were found to be variable in copy number among human populations (i.e. RHD, CFHR1, CFHR3 and PRSS1). These loci and others could explain differences in disease predisposition among individuals from different populations and could provide important clues on the adaptation of humans to different environments.
A full survey of common copy number variation in the human genome
Presentation Time: Tuesday, 11:15 a.m. - 11:30 a.m.
R. Redon1, D. F. Conrad1, L. Feuk2, C. Lee3, S. W. Scherer2, M. E. Hurles1, N. P. Carter1;
1Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 2The Hospital for Sick Children, Toronto, ON, Canada, 3Brigham and Women’s Hospital, Boston, MA, United States.
Presentation Number: C13.3
Copy number variation (CNV) in the genome is extensive and yet is grossly under-ascertained. As smaller CNVs are expected to be far more numerous than larger CNVs, improved CNV detection resolution will dramatically increase the numbers of known CNVs. The Genome Structural Variation Consortium has performed comparative genome hybridisation on a genome-wide set of tiling oligonucleotide arrays to discover the majority of common copy number variants >500bp in size in two populations with African and European ancestry. This set covers the assayable portion of the human genome with 42,000,000 probes with a median spacing of ~50bp. In addition we have generated data on a single chimpanzee to provide information on the ancestral state of observed variants. The results reveal, as expected, that previous surveys captured only 5-10% of the CNVs within a single genome. Because the boundaries of thousands of CNVs are defined precisely by this probe set, we can identify accurately functional sequences included in copy number variable regions. This provides new insights into the mechanisms generating chromosomal rearrangements and the biological functions of common CNVs.
A high-resolution structural variation map of a human genome by next-generation, high-throughput paired-end sequencing
Presentation Time: Sunday, 3:15 p.m. - 3:30 p.m.
F. M. De La Vega1, H. E. Peckham2, S. S. Ranade2, S. F. McLaughlin2, C. C. Lee2, Y. Fu2, Z. Zhang1, F. C. L. Hyland1, C. L. Clouser2, A. A. Antipova2, J. M. Manning2, C. L. Hendrickson2, L. Zhang2, E. T. Dimalanta2, T. D. Sokolsky2, M. W. Laptewicz2, B. E. Coleman2, J. K. Ichikawa2, J. B. Warner2, B. Li1, J. M. Kidd3, J. A. Malek4, G. L. Costa2, E. E. Eichler3, K. J. McKernan2;
1Applied Biosystems, Foster City, CA, United States, 2Applied Biosystems, Beverly, MA, United States, 3HHMI, University of Washington, Seattle, WA, United States, 4Weill Cornell Medical College in Qatar, Doha, Qatar.
Presentation Number: C05.2
The human genome and HapMap projects have considerably increased our understanding of the role of sequence variation in evolution and disease. Hybridization microarrays and fosmid-end sequencing reveal that structural variants (SVs) including insertions, deletions, duplications, inversions and translocations are common and extensive. Microarray methods, however, lack resolution and are blind to unbalanced events, while clone-based end-sequencing is time consuming and expensive. Here, we present a high-resolution survey of SVs of a human genome, a HapMap Yoruba sample (NA18507), by ultra-high throughput sequencing of paired-end libraries with the AB SOLiD(TM) System. We sequenced a variety of 2x25-bp paired-end libraries (>15Gb) with insert sizes ranging from 600bp to 6kb (SD 10-23%). Each library provides over 10x physical (clone) coverage, with a total combined physical coverage >60x for 90% of the genome. The high physical coverage and diverse insert sizes allowed detecting small indels within tags (1-10 bp), and approximately 70,000 indels of length 20 bp to >100 kb. Additionally, we sequenced 7Gb of 50-bp fragment libraries, which combined with the paired libraries provided over 12x sequence coverage, allowing us to discover millions of SNPs of which 75% are found in dbSNP. Inferred SVs were compared to a database of end-sequence pairs of 10x physical coverage obtained by di-deoxy sequencing of 40kb fosmid ends. A subset of novel SVs were validated by PCR and Sanger sequencing. Our results serves as a model for further high-resolution exploration of genetic variation in human populations and cancer with next-generation sequencing.
Genetic variation in India
Some recent papers from the open-access International Journal of Human Genetics.
The quality of submissions published in this journals seems to be highly variable. I know I'll be waiting with bated breath for this forthcoming paper:
Int J Hum Genet, 8(1-2): 21-29 (2008)
The Grandest Genetic Experiment Ever Performed on Man? A Y-Chromosomal Perspective on Genetic Variation in India (pdf )
Denise R. Carvalho-Silva and Chris Tyler-Smith
KEYWORDS Y chromosome; genetic variation; Indian caste system; endogamy; population substructure
We have analysed Y-chromosomal data from Indian caste, Indian tribal and East Asian populations in order to investigate the impact of the caste system on male genetic variation. We find that variation within populations is lower in India than in East Asia, while variation between populations is overall higher. This observation can be explained by greater subdivision within the Indian population, leading to more genetic drift. However, the effect is most marked in the tribal populations, and the level of variation between caste populations is similar to the level between Chinese populations. The caste system has therefore had a detectable impact on Y-chromosomal variation, but this has been less strong than the influence of the tribal system, perhaps because of larger population sizes in the castes, more gene flow or a shorter period of time.
Int J Hum Genet, 8(1-2): 41-50 (2008)
Language Shift by Indigenous Population: A Model Genetic Study in South Asia (pdf)
Gyaneshwer Chaubey, Mait Metspalu, Monika Karmin, Kumarasamy Thangaraj, Siiri Rootsi, Juri Parik, Anu Solnik, Deepa Selvi Rani, Vijay Kumar Singh, B. Prathap Naidu, Alla G. Reddy, Ene Metspalu1, Lalji Singh, Toomas Kivisild and Richard Villems
KEYWORDS Mushar; language shift; mtDNA; Y-chromosome
Language shift is a phenomenon where a new language is adopted by a population with virtually no influence on its genetic makeup. We report here the results of a case study, carried out on the Mushar populations, which is thought to have undergone language shift from Munda (an Austro-Asiatic language) to Hindi (an Indo- European language). We compared the mtDNA and Y-chromosomal phylogenies of this population with those of the neighbouring Indo-European and Austro-Asiatic speaking populations, standing at similar social status. The results revealed much closer genetic affinity of the Mushar people to the neighbouring Austro-Asiatic (Mundari) populations, than to the neighbouring Hindi-speaking populations. This example shows that the language shift as such is not necessarily a signal for a rapid genetic admixture, either maternally or paternally.
Int J Hum Genet, 8(1-2): 31-39 (2008)
Molecular Genetic Study on the Status of Transitional Groups of Central India: Cultural Diffusion or Demic Diffusion? (pdf)
Vikrant Kumar et al.
KEYWORDS Genetic status; Dravidians; Indo-Europeans; Austro-Asiatics; Central India
Two different models of diffusion - demic and cultural - have been proposed as an explanation for the spread of languages. Recent studies have shown that in some cases the dispersal of the language was due to the demic diffusion while for others it is purely due to the process of acculturation. There are four major linguistic families in India which have largely their own geographic domain. However, there are a few situations in which the populations affiliated to different linguistic families cohabit. For example, we find the spread of the Indo-European and Dravidian tribal populations in the core/peripheral areas of the Mundari Austro-Asiatic groups. These non-Mundari groups have been termed as transitional populations to indicate that these populations originally were probably Mundaris. However, there has been no attempt to ascertain if these populations are genetically Austro-Asiatics or do they belong to the linguistic groups that they are currently affiliated to. To examine this we have analysed Y-SNPs and STRs data of the 13 Mundari and 7 transitional groups and compared with the other populations of relevant linguistic groups. The results suggest that the Indo-European transitional groups are genetically Mundari and have acquired the present language through the process of cultural diffusion, while in the case of Dravidian transitional groups, the spread of language seems to be due to the process of both, the demic and cultural diffusion.
Int J Hum Genet, 8(1-2): 97-118 (2008)
Genetic Imprints of Pleistocene Origin of Indian Populations: A Comprehensive Phylogeographic Sketch of Indian Y-Chromosomes (pdf)
R. Trivedi et al.
KEYWORDS Population genetics, people of india, linguistic groups, migration
Paleoanthropological evidence indicates that modern humans reached South Asia in one of the first dispersals out of Africa, which were later followed by migrations from different parts of the world. The variation of 20 microsatellite and 38 binary polymorphisms on the non-recombining part of the uniparental, hapliod Y-chromosome was examined in 1434 male individual of 87 different populations of India to investigate various hypothesis of migration and peopling of South Asia Sub-continent. This study revealed a total of 24 paternal lineages, of which haplogroups H, R1a1, O2a and R2 portrayed for approximately 70% of the Indian Y-Chromosomes. The high NRY diversity value (0.893) and coalescence age of approx. 45-50 KYA for H and C haplogroups signified an early settlement of the subcontinent by modern humans. Haplogroup frequency and AMOVA results provide similar evidence in support of a common Pleistocene origin of Indian populations, with partial influence of Indo-European gene pool on the Indian society. The differential Y-chromosome and mt DNA pattern in the two Austric speakers of India signaled that an earlier male–mediated exodus from South East Asia largely involved the Austro-Asiatic tribes, while the Tibeto-Burman males migrated with females through two different routes; one from Burma most likely brought the Naga-Kuki-Chin language and O3e Y-chromosomes and the other from Himalayas, which carried the YAP lineages into northern regions of subcontinent. Based on distribution of Y-chromosome haplogroups (H, C, O2a, and R2) and deep coalescing time depths for these paternal lineages, we propose that the present day Dravidian speaking populations of South India are the descendants of earliest Pleistocene settlers while Austro-Asiatic speakers came from SE Asia in a later migration event.
Int J Hum Genet, 8(1-2): 1-20 (2008)
Trends in Molecular Anthropological Studies in India (pdf)
Vikal Tripathy et al.
KEYWORDS Population structure; molecular anthropology; mtDNA; Y-chromosome; autosomal DNA; India
Indian population is characterized by wide diversity and unique population structure shaped by different waves of migration and the practice of caste endogamy. Anthropologists have been studying the peopling of India and the relationships between different populations using traditional genetic markers. With the advent of molecular genetic techniques the focus has turned to using the DNA polymorphisms for resolving different anthropological questions and to test the different hypotheses in vogue. In this paper we make an attempt to critically review the trends in molecular anthropological studies till date and bring out salient features of the findings. An attempt has been made to evaluate the merit of the molecular studies in the perspective of unique population structure of India.
The quality of submissions published in this journals seems to be highly variable. I know I'll be waiting with bated breath for this forthcoming paper:
REF. NO. IJHG-362
ACCEPTED
Origin and Spread of Dravidian Speakers
Clyde Winters
Uthman dan Fodio Institute, Chicago, Illinois 60643, USA
E-mail: c-winters@govst.edu
Ancestry analysis (ESHG 2008 abstracts)
European Human Genetics Conference (abstract database)
The genome-wide patterns of variation confirms significant substructure in a founder population
K. Rehnström1,2, E. Jakkula1,3, T. Varilo1,2, O. Pietiläinen1, T. Paunio1, N. Pedersen4, M. Järvelin5, S. Ripatti1,4, S. Purcell3, M. Daly3, A. Palotie3,6, L. Peltonen1,6;
1National Public Health Institute, Helsinki, Finland, 2University of Helsinki, Helsinki, Finland, 3Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, United States, 4Karolinska Institute, Stockholm, Sweden, 5Imperial College, London, United Kingdom, 6Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
Presentation Number: P07.051
The genome-wide SNP genotyping platforms enable detailed association studies, but at the same time offer new insight into population genetics. Here we present an example of a founder population by scrutinizing nine geographically distinct Finnish subpopulations representing different eras in the population history to study the effect of bottlenecks and isolation using high-density SNP data. We demonstrate that population substructure and even individual ancestry are detectable at high resolution and support the concept of multiple historical bottlenecks resulting from founder effects.
We performed multidimensional scaling (MDS) of pairwise identity-by state (IBS) sharing data to delineate population structure. Within Finland the two primary dimensions of the MDS-analysis correspond remarkably with the east-west and north-south directions, respectively, showing a distribution of individuals corresponding closely with the geographical distribution of parents’ birthplaces. The youngest subisolates showed higher IBS similarity compared to other subgroups and separation using an extremely fine resolution. We analyzed linkage disequilibrium (LD) and extended regions of homozygosity (ROHs) to further explore the genomic structure of the subpopulations. Highest LD and the largest number of long (>10Mb) ROHs was identified in the youngest regional population and showed a gradual decline of these measures in older and more outbred, subpopulations.
The study shows the power of GWA data to trace the population history and also exemplifies the power to identify stratification even within homogeneous populations. A deeper insight into fine-scale population substructure also emphasizes the importance of adjustment of GWA studies aiming at identifying smaller and smaller genetic effects to avoid confounding.
Comparison of different methods to estimate genetic ancestry and control for stratification in genome-wide association studies
Presentation Time: Tuesday
E. Salvi1,2, G. Guffanti1, A. Orro2, F. Torri1, S. Lupoli3, J. Turner4, D. Keator4, J. Fallon4, S. Potkin4, C. Barlassina1, D. Cusi1, L. Milanesi2, F. Macciardi1;
1Department of Science and Biomedical Technology, University of Milan, Milan, Italy, 2ITB CNR, Segrate, Milan, Italy, 3INSPE, Milan, Italy, 4Department of Psychiatry and Human Behavior University of California, Irvine, CA, United States.
Presentation Number: C13.6
In case-control association studies, population subdivision or admixture can lead to spurious associations between a phenotype and unlinked candidate loci. Population stratification can occur in case-control association studies when allele frequencies differ between cases and controls because of ancestry.
We evaluated five methods (Fst, Genomic Control, STRUCTURE, PLINK and EIGENSTRAT) using 317K SNPs (Illumina HumanHap300) in a case-control sample of 200 American subjects with different races (Caucasian, African and Asian) in order to identify and to correct for stratification. Fst, Structure and Genomic Control are based on the usage of few genetic markers while PLINK and EIGENSTRAT are computationally tractable on a genome-wide scale. Fst, STRUCTURE and Genomic Control did not detect a significant stratification in our sample, as well as EIGENSTRAT and PLINK. However, these last two methods, using a much larger information from the whole set of SNPs, graphically suggested the presence of a partial stratification, due to African and Asian individuals while the estimated inflation factor of 1 didn't statistically confirm stratification. This brought to the decision to further enlarge the sample with hundreds of controls coming from Caucasian populations. When we enlarged the sample to 650 individuals we found a high value of inflation factor as statistical confirmation of the population stratification. The substructure still depends only on African and Asian subjects that are separated from the Caucasian homogeneous sample. Therefore the sample size is crucial to get enough power to detect a possible stratification.
A computational test for biological relatedness in genetic association studies using probabilistically inferred haplotypes
L. Xumerle, G. Malerba, P. F. Pignatti;
Department Maternal Infantile and of Biology-Genetics. Section of Biology and Genetics, University of Verona, Italy.
Presentation Number: P06.058
An association between gene and disease may be incorrectly estimated if the allele frequencies differ among cases and controls depending on inbreeding or unrecognized population stratification.
A program (http://medgen.univr.it/jenoware/) was developed to compute the probability of genetic relatedness in pairs of individuals using a likelihood ratio test.
Using loci that are in LD decreases the accuracy of parentage assignments. Groups of SNPs in linkage disequilibrium (LD) were simulated to verify the effects of linkage on relatedness assignment. The probability of genetic relatedness was computed using the single SNPs and treating the SNPs as composite markers with different r² threshold values. Haplotypes were probabilistically inferred using the PHASE and Gerbil programs. False positive rate and power were assessed by simulation in unrelated individuals and in pedigrees.
As an example of results, in order to estimate the support for II degree relatedness with power 80%, and false positive rate 5%, the following was needed: 100 SNPs with no linkage; 275 SNPs having r²=0.4; 20 probabilistically inferred haplotypes (100 SNPs having r²=0.4); 40 probabilistically inferred haplotypes (200 SNPs having r²=0.8).
In conclusion, if LD blocks are examined, the biological relatedness can be computed with a limited number of markers increasing test accuracy with probabilistically inferred haplotypes.
The genome-wide patterns of variation confirms significant substructure in a founder population
K. Rehnström1,2, E. Jakkula1,3, T. Varilo1,2, O. Pietiläinen1, T. Paunio1, N. Pedersen4, M. Järvelin5, S. Ripatti1,4, S. Purcell3, M. Daly3, A. Palotie3,6, L. Peltonen1,6;
1National Public Health Institute, Helsinki, Finland, 2University of Helsinki, Helsinki, Finland, 3Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, United States, 4Karolinska Institute, Stockholm, Sweden, 5Imperial College, London, United Kingdom, 6Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
Presentation Number: P07.051
The genome-wide SNP genotyping platforms enable detailed association studies, but at the same time offer new insight into population genetics. Here we present an example of a founder population by scrutinizing nine geographically distinct Finnish subpopulations representing different eras in the population history to study the effect of bottlenecks and isolation using high-density SNP data. We demonstrate that population substructure and even individual ancestry are detectable at high resolution and support the concept of multiple historical bottlenecks resulting from founder effects.
We performed multidimensional scaling (MDS) of pairwise identity-by state (IBS) sharing data to delineate population structure. Within Finland the two primary dimensions of the MDS-analysis correspond remarkably with the east-west and north-south directions, respectively, showing a distribution of individuals corresponding closely with the geographical distribution of parents’ birthplaces. The youngest subisolates showed higher IBS similarity compared to other subgroups and separation using an extremely fine resolution. We analyzed linkage disequilibrium (LD) and extended regions of homozygosity (ROHs) to further explore the genomic structure of the subpopulations. Highest LD and the largest number of long (>10Mb) ROHs was identified in the youngest regional population and showed a gradual decline of these measures in older and more outbred, subpopulations.
The study shows the power of GWA data to trace the population history and also exemplifies the power to identify stratification even within homogeneous populations. A deeper insight into fine-scale population substructure also emphasizes the importance of adjustment of GWA studies aiming at identifying smaller and smaller genetic effects to avoid confounding.
Comparison of different methods to estimate genetic ancestry and control for stratification in genome-wide association studies
Presentation Time: Tuesday
E. Salvi1,2, G. Guffanti1, A. Orro2, F. Torri1, S. Lupoli3, J. Turner4, D. Keator4, J. Fallon4, S. Potkin4, C. Barlassina1, D. Cusi1, L. Milanesi2, F. Macciardi1;
1Department of Science and Biomedical Technology, University of Milan, Milan, Italy, 2ITB CNR, Segrate, Milan, Italy, 3INSPE, Milan, Italy, 4Department of Psychiatry and Human Behavior University of California, Irvine, CA, United States.
Presentation Number: C13.6
In case-control association studies, population subdivision or admixture can lead to spurious associations between a phenotype and unlinked candidate loci. Population stratification can occur in case-control association studies when allele frequencies differ between cases and controls because of ancestry.
We evaluated five methods (Fst, Genomic Control, STRUCTURE, PLINK and EIGENSTRAT) using 317K SNPs (Illumina HumanHap300) in a case-control sample of 200 American subjects with different races (Caucasian, African and Asian) in order to identify and to correct for stratification. Fst, Structure and Genomic Control are based on the usage of few genetic markers while PLINK and EIGENSTRAT are computationally tractable on a genome-wide scale. Fst, STRUCTURE and Genomic Control did not detect a significant stratification in our sample, as well as EIGENSTRAT and PLINK. However, these last two methods, using a much larger information from the whole set of SNPs, graphically suggested the presence of a partial stratification, due to African and Asian individuals while the estimated inflation factor of 1 didn't statistically confirm stratification. This brought to the decision to further enlarge the sample with hundreds of controls coming from Caucasian populations. When we enlarged the sample to 650 individuals we found a high value of inflation factor as statistical confirmation of the population stratification. The substructure still depends only on African and Asian subjects that are separated from the Caucasian homogeneous sample. Therefore the sample size is crucial to get enough power to detect a possible stratification.
A computational test for biological relatedness in genetic association studies using probabilistically inferred haplotypes
L. Xumerle, G. Malerba, P. F. Pignatti;
Department Maternal Infantile and of Biology-Genetics. Section of Biology and Genetics, University of Verona, Italy.
Presentation Number: P06.058
An association between gene and disease may be incorrectly estimated if the allele frequencies differ among cases and controls depending on inbreeding or unrecognized population stratification.
A program (http://medgen.univr.it/jenoware/) was developed to compute the probability of genetic relatedness in pairs of individuals using a likelihood ratio test.
Using loci that are in LD decreases the accuracy of parentage assignments. Groups of SNPs in linkage disequilibrium (LD) were simulated to verify the effects of linkage on relatedness assignment. The probability of genetic relatedness was computed using the single SNPs and treating the SNPs as composite markers with different r² threshold values. Haplotypes were probabilistically inferred using the PHASE and Gerbil programs. False positive rate and power were assessed by simulation in unrelated individuals and in pedigrees.
As an example of results, in order to estimate the support for II degree relatedness with power 80%, and false positive rate 5%, the following was needed: 100 SNPs with no linkage; 275 SNPs having r²=0.4; 20 probabilistically inferred haplotypes (100 SNPs having r²=0.4); 40 probabilistically inferred haplotypes (200 SNPs having r²=0.8).
In conclusion, if LD blocks are examined, the biological relatedness can be computed with a limited number of markers increasing test accuracy with probabilistically inferred haplotypes.
2008-05-23 links
Intelligence and class: Social class IQ differences and university access (via Sailer)
Personal genomics: How To Use SNPedia for 23andMe and deCODEme
Basic statistics: Error bars in experimental biology (via bayblab)
Personal genomics: How To Use SNPedia for 23andMe and deCODEme
Basic statistics: Error bars in experimental biology (via bayblab)
Subscribe to:
Posts (Atom)