title: Multiallelic Positions in the Human Genome: Challenges for Genetic Analyses.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Campbell
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Jhangiani
authors.affiliation: Human Genetics Center, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Veeraraghavan
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.|Human Genetics Center, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Fuli
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.|Texas Children's Hospital, Houston, TX 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000483:Alleles; D059472:Exome / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans
keywords: human variation; multiallelic; paralogous sequence variant; pathogenic variant; single-nucleotide variant