Exome-wide survey of the Siberian Caucasian population

Andrey A Yurchenko,Mikhail I Voevoda,Nikolai S Yudin

doi:10.1186/s12881-019-0772-4

Abstract

BackgroundPopulation structure is an important factor in the genetic association studies but often remains underexplored for many human populations. We identified exome variants in 39 Siberian Caucasian individuals from Novosibirsk, Russia and compared their genetic allele frequencies with European populations from 1000 Genomes Project.MethodsThe study participants were from Novosibirsk and represented people with monogenic diabetes, healthy individuals and a cohort from the tick-borne encephalitis study. Isolated DNA was enriched using Agilent SureSelect V5 kit and sequenced on Illumina HiSeq 4000 and genetic variants were identified using GATK pipeline. To estimate the patterns of the population structure we used PCA and ADMIXTURE analysis. Pharmocogenetically and medically important variants were annotated based on PharmGKB and ClinVar databases.ResultsThe analysis identified low, but highly significant population differentiation attributed to numerous loci between the Siberian Caucasian population and other European population samples as well as a higher proportion of the Finnish genetic component in the studied sample. The medical and pharmacogenetic annotation of highly significantly differentiated variants between the Novosibirsk and the combined European populations revealed a number of important genetic polymorphisms located in such genes as FCGR3B, TYR, OCA2, FABP1, CHEK2 and SLC4A1.ConclusionsThe study reports for the first time an exome-wide comparison of a population from Russia with European samples and emphasizes the importance of population studies with medical annotation of variants.

Highlights

Population structure is an important factor in the genetic association studies but often remains underexplored for many human populations
We identified exome genetic variants for 39 individuals from Novosibirsk, Russia and compared them with the previously published genome-wide data and exomes of European populations from the 1000 Genomes Project to understand the level of the exome-wide divergence and the extent of the population stratification
In ADMIXTURE analysis, the lowest value of the Cross Validation Error was attributed to the K = 2, which captured the divergence of FIN from other European populations

Summary

Introduction

Population structure is an important factor in the genetic association studies but often remains underexplored for many human populations. We identified exome variants in 39 Siberian Caucasian individuals from Novosibirsk, Russia and compared their genetic allele frequencies with European populations from 1000 Genomes Project. Population structure is a very important factor in medical genetic association studies which can compromise modern genomic methods not being properly accounted for. We identified exome genetic variants for 39 individuals from Novosibirsk, Russia and compared them with the previously published genome-wide data and exomes of European populations from the 1000 Genomes Project to understand the level of the exome-wide divergence and the extent of the population stratification. We tested allele frequency differences between our sample and combined European dataset for medically and pharmacogenetically important variants to identify loci which can be important for national studies.

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Results

Conclusion