title: Extensive genome-wide autozygosity in the population isolates of Daghestan.
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.
authors.affiliation: ARL Division of Biotechnology, University of Arizona, Tucson, AZ, USA.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Karafet
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Kazima B
authors.initials: KB
authors.lastname: Bulayeva
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Bulayev
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Farida
authors.initials: F
authors.lastname: Gurgenova
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Jamilia
authors.initials: J
authors.lastname: Omarova
authors.affiliation: Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenia.
authors.forename: Levon
authors.initials: L
authors.lastname: Yepiskoposyan
authors.affiliation: ARL Division of Biotechnology, University of Arizona, Tucson, AZ, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Savina
authors.affiliation: ARL Division of Biotechnology, University of Arizona, Tucson, AZ, USA.
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Veeramah
authors.affiliation: ARL Division of Biotechnology, University of Arizona, Tucson, AZ, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hammer
mesh_terms: D001208:Asia; D002874:Chromosome Mapping / Q000379:methods; D003241:Consanguinity; D005060:Europe; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007178:Inbreeding / Q000379:methods; D015810:Linkage Disequilibrium / Q000235:genetics; D008877:Middle East; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*