Extensive genome-wide autozygosity in the population isolates of Daghestan - PubMed (original) (raw)

Extensive genome-wide autozygosity in the population isolates of Daghestan

Tatiana M Karafet et al. Eur J Hum Genet. 2015 Oct.

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Approximate geographic location of sampling sites. Of the 20 Daghestanian populations sampled here, 14 speak unique languages that are part of the ND language family. Of the remaining six populations (non-ND), three speak languages that are closely related to the Turkic branch of Altaic language family (Kumyks, Nogais and Azerbaijans), and three speak languages belonging to the Iranian language branch of the Indo-European language family (ethnic Tats, Mountain Jews and a group of Azerbaijans originated in Iran). See Supplementary Table 1 for population codes. ND and non-ND populations are shown in circle and triangle, respectively.

Figure 2

Figure 2

PCA analysis using the ‘drop one in' technique for 56 populations. Circled positions indicate the median coordinate values for populations. See Supplementary Table 1 for population codes.

Figure 3

Figure 3

Distribution of total length of different ROH classes per individual in 40 populations. A box plot and a kernel density plot are shown as ‘violin plots' for classes A (a), B (b), C (c) and A, B, C classes pooled together (d). The white horizontal line is the median, whereas the black bar represents the interquartile range. Populations are grouped according to geographic regions.

Figure 4

Figure 4

Regional distribution of ROH. The mean total ROH length (Mb)±SE is plotted for each geographic region.

Figure 5

Figure 5

The harmonic mean of _N_e for each population with sample size _N_≥10 over 50 recombination distance classes between 0.005 and 0.25 cM with increment 0.005 cM. The SEs for _N_e indicated by the bars were derived from separate analysis of each autosomal chromosome. Yorubans were included for comparisons with published data.

Similar articles

Cited by

References

    1. 1Acevedo-Whitehouse K, Gulland F, Greig D, Amos W: Inbreeding: disease susceptibility in California sea lions. Nature 2003; 422: 35. - PubMed
    1. 2Bittles A: Consanguinity and its relevance to clinical genetics. Clin Genet 2001; 60: 89–98. - PubMed
    1. 3Bittles AH, Black ML: Evolution in health and medicine Sackler colloquium: consanguinity, human evolution, and complex diseases. Proc Natl Acad Sci USA 2010; 107 (Suppl 1): 1779–1786. - PMC - PubMed
    1. 4Nalls MA, Guerreiro RJ, Simon-Sanchez J et al: Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer's disease. Neurogenetics 2009; 10: 183–190. - PMC - PubMed
    1. 5Charlesworth D, Willis JH: The genetics of inbreeding depression. Nat Rev Genet 2009; 10: 783–796. - PubMed

Publication types

MeSH terms

LinkOut - more resources