The Impact of the Turkish Population Variome on the Genomic Architecture of Rare Disease Traits

Authors

Zeynep Coban-Akdemir
Xiaofei Song
Francisco C Ceballos
Davut Pehlivan
Ender Karaca
Yavuz Bayram
Tadahiro Mitani
Tomasz Gambin
Tugce Bozkurt-Yozgatli
Shalini N Jhangiani
Donna M Muzny
Richard A Lewis
Pengfei Liu
Eric Boerwinkle
Ada Hamosh
Richard A Gibbs
V Reid Sutton
Nara Sobreira
Claudia M B Carvalho
Chad A Shaw
Jennifer E Posey
David Valle
James R Lupski

Publication Date

2-14-2024

Journal

Genetics in Medicine Open

Abstract

PURPOSE: The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease.

METHODS: We generated and analyzed a database of variants derived from exome sequencing data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits and 643 unaffected relatives.

RESULTS: Using uniform manifold approximation and projection, we showed that the TK genomes are more similar to those of Europeans and consist of 2 main subpopulations: clusters 1 and 2 (

CONCLUSION: Our findings support the notion that novel rare variants on newly configured haplotypes arising within the recent past generations of a family or clan contribute significantly to recessive disease traits in the TK population.

Keywords

Admixture, Consanguinity, Genomic architecture of rare disease traits, Runs of homozygosity, Turkish population

PMCID

PMC11613692

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