NEW YORK — A genomic analysis of the Turkish population has uncovered high levels of variation, highlighting the influence of historical and more recent events on the people of modern-day Turkey.
Researchers led by Tayfun Özçelik, a professor of human genetics at Bilkent University in Turkey, sequenced and analyzed the exomes or genomes of nearly 4,000 individuals from across Anatolia. When they compared the results to those of other populations, they noted close ties to Balkan, Caucasus, Middle Eastern, and European populations, but also uncovered a number of variants within the Turkish population that were not present in public databases, underscoring the need for a population-specific repository.
"We anticipated that the level of variation and admixture would be higher than that of European populations, based on the history of Anatolia," Özçelik wrote in an email. "However, we were surprised by the extent of variation and admixture we observed in the Turkish population."
By identifying variants with potential functional consequences, the researchers further developed a Turkish Variome database to bolster disease gene discovery. They reported their results in a paper appearing on Monday in the Proceedings of the National Academy of Sciences.
Özçelik and his colleagues analyzed exome or genome data from 3,864 individuals, of which 3,362 passed quality controls and checks for relatedness. For 1,460 samples, the researchers knew the geographical origins of the individuals' grandparents, which they clustered into six subregions: Balkan, West, Central, North, South, and East Turkey.
Using principal components analysis and the Admixture algorithm, the researchers found that their cohort had four major ancestral components — European, Balkan, Caucasus, and Middle Eastern — that varied slightly by geography. The European and Balkan contributions, for instance, were higher in the Balkan and Western subregions.
These findings are in line with Turkey's history of being a crossroads of ancient migrations, historical expansions and conquests, and a more recent influx of Balkan individuals in 1914, the researchers noted.
Their analysis also identified nearly 10 million novel variants, 37,123 of which they determined were likely to be deleterious. Additionally, about 21 percent of all the variants they uncovered were specific to the Turkish population and about 38 percent of the private deleterious variants were not found in public databases.
This included the Greater Middle Eastern Variome, which has about 100 Turkish samples, they noted, suggesting that these do not adequately represent the Turkish population. This finding "emphasizes the necessity of generating a Turkish Variome with higher sample size," Özçelik said.
The Turkish Variome he and his colleagues developed includes 839,775 novel or rare variants with a frequency of 1 percent or higher in the Turkish population. This database, the researchers noted, better reflects the genetic background of Turkey and can be used to fuel human and medical genetics studies. It also includes annotations of the variants' functional consequences and a Turkish reference panel for genotype imputations.
The team noted that the Greater Middle Eastern Variome has demonstrated the power of consanguinity to identify causes of recessive genetic disease. Since consanguineous marriages are common in Turkey, the publicly available Turkish Variome could also contribute to this end, they suggested. "We believe the Turkish Variome will be an invaluable resource for numerous research," Özçelik said.
He added that he and his colleagues are evaluating secondary findings within the Turkish Variome, including those on the American College of Medical Genetics and Genomics list, and are determining the carrier frequencies for recessive diseases.