The genetic structure of the Turkish population reveals high levels of variation and admixture

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 50% 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.

Comparative Analyses of Turkish Variome and Widely Used Genomic Variation Databases for the Evaluation of Rare Sequence Variants in Turkish Individuals: Idiopathic Hypogonadotropic Hypogonadism as a Disease Model

“…Our study using a rare disease model, IHH, which is not represented in the TRV patient subpopulations, confirms that TRV is well representative of the Turkish population. Kars et al ( 9 ) also reported the close genetic relationship between Balkan and Caucasian populations and those of Turkey. Previously, similar to our methods paradigm, Alkan et al ( 5 ) studied the 16 genomes from various regions of Turkey and compared them to those in the 1000 Genomes Project, and showed that the genetic structure of the people of Turkey is similar to those of Europe, particularly the Southern Europe/Mediterranean region, compared to other gene pools.…”

“…The genetic structure of Turkish people has been investigated in small scale studies using different methods ( 5 , 6 , 7 , 8 ). In a recent study, Kars et al ( 9 ) published the first comprehensive genomic variation database, Turkish Variome (TRV), which compiles whole genome and whole exome data from 3362 individuals from various regions of Turkey.…”

Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation

“…Exome sequencing analysis was performed, including MS cases (N = 25) and unaffected family members older than 50 years of age (N = 13), revealing 42 heterozygous and 1 homozygous fully penetrant, rare or low-frequency, exonic variants (Supplementary Table S3 ). All variants were rare or low-frequency both in the gnomAD (all populations) and Turkish population based on the work by Kars et al 15 . Thirty of the heterozygous variants were located in the candidate linkage regions in family FMS01, and the homozygous variant detected in family FMS02 was located in the homozygous region with a size of 539 kb and a LOD score of 1.2 (Table 1 ).…”

“… NA not available. *Variant frequencies in the Turkish population based on the work by Kars et al 15 . …”

Biodiversity of Mycobacterium tuberculosis in Bulgaria Related to Human Migrations or Ecological Adaptation

“…The Ottoman Empire became an unprecedented mix of different ethnic and religious communities, numbering more than 25. Modern genetic research shows that a significant part of the 83.6 million population of the Republic of Turkey (in 2020) are not of Turkic origin and share a high degree of variation and admixture [40]. This means that the dynamic migration processes within the Ottoman Empire have led to significant biodiversity of different eastern (L1, L2, and L3) and western (L4) sublineages of M. tuberculosis.…”