Evaluation of whole exome sequencing as an alternative to BeadChip and whole genome sequencing in human population genetic analysis 06 Biological Sciences 0604 Genetics

Zoltán Maróti, Zsolt Boldogkoi, Dóra Tombácz, Michael Snyder, Tibor Kalmár

Research output: Article


Background: Understanding the underlying genetic structure of human populations is of fundamental interest to both biological and social sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation. The most widely used methods for collecting variant information at the DNA-level include whole genome sequencing, which remains costly, and the more economical solution of array-based techniques, as these are capable of simultaneously genotyping a pre-selected set of variable DNA sites in the human genome. The largest publicly accessible set of human genomic sequence data available today originates from exome sequencing that comprises around 1.2% of the whole genome (approximately 30 million base pairs). Results: To unbiasedly compare the effect of SNP selection strategies in population genetic analysis we subsampled the variants of the same highly curated 1 K Genome dataset to mimic genome, exome sequencing and array data in order to eliminate the effect of different chemistry and error profiles of these different approaches. Next we compared the application of the exome dataset to the array-based dataset and to the gold standard whole genome dataset using the same population genetic analysis methods. Conclusions: Our results draw attention to some of the inherent problems that arise from using pre-selected SNP sets for population genetic analysis. Additionally, we demonstrate that exome sequencing provides a better alternative to the array-based methods for population genetic analysis. In this study, we propose a strategy for unbiased variant collection from exome data and offer a bioinformatics protocol for proper data processing.

Original languageEnglish
Article number778
JournalBMC genomics
Issue number1
Publication statusPublished - okt. 29 2018


ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this