Analytical "bake-off" of whole genome sequencing quality for the Genome Russia project using a small cohort for autoimmune hepatitis

PLoS One. 2018 Jul 11;13(7):e0200423. doi: 10.1371/journal.pone.0200423. eCollection 2018.

Abstract

A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects. We assessed calling of SNPs, indels, copy number variation, and the speed of WGS throughput promised. Twenty separate QC analyses showed high similarities among the sequence quality and called genotypes. The ten genomes tested by the centers included eight American patients afflicted with autoimmune hepatitis (AIH), plus one case's unaffected parents, in a prelude to discovering genetic influences in this rare disease of unknown etiology. The detailed internal replication and parallel analyses allowed the observation of two of eight AIH cases carrying a rare allele genotype for a previously described AIH-associated gene (FTCD), plus multiple occurrences of known HLA-DRB1 alleles associated with AIH (HLA-DRB1-03:01:01, 13:01:01 and 7:01:01). We also list putative SNVs in other genes as suggestive in AIH influence.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Ammonia-Lyases / genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Copy Number Variations
  • Female
  • Genetic Predisposition to Disease
  • Genotyping Techniques*
  • Glutamate Formimidoyltransferase / genetics
  • HLA-DRB1 Chains / genetics
  • Hepatitis, Autoimmune / genetics*
  • Humans
  • INDEL Mutation
  • Male
  • Multifunctional Enzymes
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Quality Control
  • Russia
  • Time Factors
  • Whole Genome Sequencing*

Substances

  • HLA-DRB1 Chains
  • Multifunctional Enzymes
  • FTCD protein, human
  • Glutamate Formimidoyltransferase
  • Ammonia-Lyases

Grants and funding

Dobzhansky Center authors were supported by St. Petersburg State University (Genome Russia Grant no. 1.52.1647.2016).