Abstract
Isolated populations are valuable resources for mapping disease genes, as inbreeding increases genome-wide homozygosity and enhances the ability to map disease alleles on a genetically uniform background within a relatively homogenous environment. The populations of Daghestan are thought to have resided in the Caucasus Mountains for hundreds of generations and are characterized by a high prevalence of certain complex diseases. To explore the extent to which their unique population history led to increased levels of inbreeding, we genotyped >550 000 autosomal single-nucleotide polymorphisms (SNPs) in a set of 14 population isolates speaking Nakh-Daghestanian (ND) languages. The ND-speaking populations showed greatly elevated coefficients of inbreeding, very high numbers and long lengths of Runs of Homozygosity, and elevated linkage disequilibrium compared with surrounding groups from the Caucasus, the Near East, Europe, Central and South Asia. These results are consistent with the hypothesis that most ND-speaking groups descend from a common ancestral population that fragmented into a series of genetic isolates in the Daghestanian highlands. They have subsequently maintained a long-term small effective population size as a result of constant inbreeding and very low levels of gene flow. Given these findings, Daghestanian population isolates are likely to be useful for mapping genes associated with complex diseases.
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Acknowledgements
We thank all Daghestanian people participating in this study, August Woerner and Brian Hallmark for bioinformatics support. This work was supported by grants from the National Science Foundation (BSC 1025266 to MFH and TMK and BSC0742328 to TMK).
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Karafet, T., Bulayeva, K., Bulayev, O. et al. Extensive genome-wide autozygosity in the population isolates of Daghestan. Eur J Hum Genet 23, 1405–1412 (2015). https://doi.org/10.1038/ejhg.2014.299
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DOI: https://doi.org/10.1038/ejhg.2014.299
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