title: The landscape of human STR variation.
abstract: Short tandem repeats are among the most polymorphic loci in the human genome. These loci play a role in the etiology of a range of genetic diseases and have been frequently utilized in forensics, population genetics, and genetic genealogy. Despite this plethora of applications, little is known about the variation of most STRs in the human population. Here, we report the largest-scale analysis of human STR variation to date. We collected information for nearly 700,000 STR loci across more than 1000 individuals in Phase 1 of the 1000 Genomes Project. Extensive quality controls show that reliable allelic spectra can be obtained for close to 90% of the STR loci in the genome. We utilize this call set to analyze determinants of STR variation, assess the human reference genome's representation of STR alleles, find STR loci with common loss-of-function alleles, and obtain initial estimates of the linkage disequilibrium between STRs and common SNPs. Overall, these analyses further elucidate the scale of genetic variation beyond classical point mutations.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA; Computational and Systems Biology Program, MIT, Cambridge, Massachusetts 02139, USA;
authors.forename: Thomas
authors.initials: T
authors.lastname: Willems
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA; Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, Massachusetts 02139, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA; Department of Molecular Biology and Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
authors.forename: Melissa
authors.initials: M
authors.lastname: Gymrek
authors.affiliation: Virginia Bioinformatics Institute and Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA;
authors.forename: Gareth
authors.initials: G
authors.lastname: Highnam
authors.affiliation: Virginia Bioinformatics Institute and Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA; Gene by Gene, Ltd., Houston, Texas 77008, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mittelman
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA; yaniv@wi.mit.edu.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Erlich
mesh_terms: D000483:Alleles; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods*; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide