ESHG 2014: Genetic landscape of populations along the Silk Road

Title: P17.64-M - Genetic landscape of populations along the Silk Road reveals a haplotype associated with hyposmia in Tajikistan's population
Keywords: olfactory receptor clusters; Silk Road; population structure
Authors: M. Mezzavilla1,2, S. Ulivi2, P. Gasparini1,2, V. Colonna3; 1University of Trieste, Trieste, Italy, 2Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy, 3Institute of Genetics and Biophysics "A. Buzzati-Traverso", National Research Council (CNR), Napoli, Italy.

Abstract: Smell is a versatile mechanism for recognizing different odours and is mediated by olfactory receptors. While collecting phenotypes related to smell in six countries along the Silk Road, we found an increased rate of failure to discriminate odorants in individuals from Tajikistan respect to the other countries. Using haplotype-based association we linked this to a 15 kb region within olfactory receptor gene cluster on chromosome 6 (p-value 3.86e-05). This region is embedded in the largest intron of OR5V1 and is downstream OR11A1 and upstream OR12D3. We also analysed genetic variability in 1,114 unrelated samples either from the Silk Road and ten other worldwide populations at over 300,000 polymorphic sites and characterized population genetic structure of the Silk Road within a worldwide context with a resolution never obtained before. We identified genetic components peculiar to Central Asia and observed that Tajikistan behaves as an outlier population. Indeed Tajiks share a consistent number of unusually large stretches of homozygosity and have the lowest effective population size (Ne) among the studied populations, most likely as the result of past isolation and/or consanguinity. Altogether these novel findings clarify the complex genetic patterns of the Silk Road populations and suggest that the smell misperception phenotype observed in Tajikistan might be the result of a combination of genetic drift and relaxed selection at the olfactory receptors genes.

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