Multiallelic Positions in the Human Genome: Challenges for Genetic Analyses

Hum Mutat. 2016 Mar;37(3):231-234. doi: 10.1002/humu.22944. Epub 2015 Dec 31.


As the amount of human genomic sequence available from personal genomes and exomes has increased, so too has the observation of genomic positions having two or more alternative alleles, so-called multiallelic sites. For portions of the haploid genome that are present in more than one copy, including segmental duplications, variation at such multisite variant positions becomes even more complex. Despite the frequency of multiallelic variants, a number of commonly used resources and tools in genomic research and diagnostics do not support these multiallelic variants all together or require special modifications. Here, we explore the frequency of multiallelic sites in large samples with whole exome sequencing and discuss potential outcomes of failing to account for multiple variant alleles. We also briefly discuss some commonly utilized resources that fully support multiallelic sites.

Keywords: human variation; multiallelic; paralogous sequence variant; pathogenic variant; single-nucleotide variant.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles*
  • Exome / genetics*
  • Genome, Human / genetics*
  • Humans