A British approach to sampling:
People of the British Isles: preliminary analysis of genotypes and surnames in a UK-control population:
The acronym ‘PoBI’ may not yet be familiar to human geneticists in the way that ‘HGDP’, ‘WTCCC’ or ‘HapMap’ are, but a paper in this issue of EJHG1 that introduces the ‘People of the British Isles’ project to the scientific community aims to change this. The PoBI project will collect up to 5000 DNA samples from diverse regions of the British Isles, taking great care to sample individuals with several generations of ancestry in rural locations. These samples are intended to serve as controls for future medical genetic studies, and to provide insights into the peopling of the British Isles over the last few millennia. [. . .] Although readers will have to wait for future publications to discover the insights from these large-scale genetic analyses, the current paper describes the sampling strategy and initial 3865 samples in some detail, outlines an approach to investigating fine-scale population structure using surnames, and presents some preliminary genetic analyses of a handful of chosen loci. [. . .]
In addition to collecting blood, the project recorded surnames. Using data from a census performed in 1881, these were classified as ‘local’ or ‘non-local’, and the two classes examined separately. The authors then modelled a population such as that from central England as a mixture between south-western (taken to represent Ancient Britons) and eastern (Anglo Saxon) populations, and estimated the contribution of each population to the central England autosomal genotypes. These contributions differed between the local surname class (mostly eastern) and the non-local class (half and half), which the authors take as evidence of subtle population structure. Published genetic analyses using much larger numbers of markers have already detected low, but significant levels of genetic structure within Britain in more straightforward ways,4, 5 even with less stringently ascertained samples (Figure 1): Europe-wide south-east to north-west gradients extend into the British Isles. We can look forward to deeper insights into genetic differentiation and its causes when large-scale genetic analyses of the PoBI samples are available.
[. . .] anthropological and evolutionary geneticists should rejoice in the assembly of this resource, the foresight of The Wellcome Trust in funding the project over a decade or so, and hope that resources are available for establishing more cell lines and performing more genome-wide sequencing, so that both the full set of samples and their sequences can be made widely available.
It is obvious why British people interested in their ancestry, and medical geneticists working with British subjects should welcome PoBI, but why should others pay attention? PoBI will not provide information about global genetic diversity in the way that HGDP7 and HapMap8 do, but its microcosmic survey of genetic variation in a set of small islands off the western coast of the Eurasian continent is revealing the level of differentiation that builds up over millennia via events well documented by archaeology and history, so these alternative data sets can be compared to address questions about the initial peopling of the area, and its subsequent reshaping by internal and external forces. And if the characteristics of the British – politeness, eccentricity, or drunken loutishness, according to your viewpoint and experience – have any genetic basis, perhaps PoBI can provide a starting point for identifying it!
There is a great deal of interest in a fine-scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to have a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. In this study, we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK-control population that can be used as a resource by the research community, as well as providing a fine-scale genetic information on the British population. So far, some 4000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3 km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1057 samples demonstrates the value of these samples for investigating a fine-scale population structure within the UK, and shows how this can be enhanced by the use of surnames.
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