A genomic view of short tandem repeats.pdfVIP

Available online at ScienceDirect A genomic view of short tandem repeats Melissa Gymrek1,2 Short tandem repeats (STRs) are some of the fastest mutating loci in the genome. Tools for accurately pro?ling STRs from high-throughput sequencing data have enabled genome-wide interrogation of more than a million STRs across hundreds of individuals. These catalogs have revealed that STRs are highly multiallelic and may contribute more de novo mutations than any other variant class. Recent studies have leveraged these catalogs to show that STRs play a widespread role in regulating gene expression and other molecular phenotypes. These analyses suggest that STRs are an underappreciated but rich reservoir of variation that likely make signi?cant contributions to Mendelian diseases, complex traits, and cancer. Addresses 1 Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA 2 Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA Corresponding author: Gymrek, Melissa (mgymrek@) Current Opinion in Genetics Development 2017, 44:9–16 This review comes from a themed issue on Molecular and genetic bases of disease Edited by Nancy Bonini, Edward Lee and Wilma Wasco /10.1016/j.gde.2017.01.012 0959-437X/? 2017 Elsevier Ltd. All rights reserved. Introduction Short tandem repeats (STRs), also known as microsatellites, consist of repeating motifs of 1–6 base pairs (bp) and comprise about 3% of the human genome [1]. Their repetitive nature induces slippage events during DNA replication that result in frequent mutations in the number of repeats. As a result, STRs exhibit mutation rates that are orders of magnitude higher than other types of variation [2], and thus contribute a large fraction of human genetic variation. A role for STRs in human disease was established over two decades ago, with independent discoveries of trinucleotide expansions resulting in Fragile X Syndrome [3,4] and spinal and bulbar musc