Abstract
The construction of population-based variomes has contributed substantially to our understanding of the genetic basis of human inherited disease. Here, we investigated the genetic structure of Turkey from 3,362 unrelated subjects whose whole exomes (n = 2,589) or whole genomes (n = 773) were sequenced to generate a Turkish (TR) Variome that should serve to facilitate disease gene discovery in Turkey. Consistent with the history of present-day Turkey as a crossroads between Europe and Asia, we found extensive admixture between Balkan, Caucasus, Middle Eastern, and European populations with a closer genetic relationship of the TR population to Europeans than hitherto appreciated. We determined that 30% of TR individuals had high inbreeding coefficients (≥0.0156) with runs of homozygosity longer than 4 Mb being found exclusively in the TR population when compared to 1000 Genomes Project populations. We also found that 28% of exome and 49% of genome variants in the very rare range (allele frequency < 0.005) are unique to the modern TR population. We annotated these variants based on their functional consequences to establish a TR Variome containing alleles of potential medical relevance, a repository of homozygous loss-of-function variants and a TR reference panel for genotype imputation using high-quality haplotypes, to facilitate genome-wide association studies. In addition to providing information on the genetic structure of the modern TR population, these data provide an invaluable resource for future studies to identify variants that are associated with specific phenotypes as well as establishing the phenotypic consequences of mutations in specific genes.
Funder
TUBITAK
TUBA Principal Investigator Support
Suna and Inan Kirac Foundation
National Human Genome Research Institute and the National Heart, Lung, and Blood Institute
The GSP Coordinating Center
JPB Foundation
National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program
National Institutes of Health
The French National Research Agency (ANR) under the 'Investments for the future' program
Integrative Biology of Emerging Infectious Diseases Laboratoire d'Excellence
IEIHSEER grant
SEAe-HostFactors grant
PNEUMOID project
INCA/Cancéropole Ile-de-France
Publisher
Proceedings of the National Academy of Sciences
Reference56 articles.
1. Genomic history of neolithic to bronze age Anatolia, northern Levant, and southern Caucasus;Skourtanioti;Cell,2020
2. P. B. Golden , An Introduction to the History of the Turkic Peoples. Ethnogenesis and State-Formation in Medieval and Early Modern Eurasia and the Middle East (Otto Harrassowitz, Wiesbaden, 1992).
3. Excavating Y-chromosome haplotype strata in Anatolia
4. The frequency of consanguineous marriage in eastern Turkey;Akbayram;Genet. Couns.,2009
5. Consanguinity, human evolution, and complex diseases
Cited by
42 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献