Recent advances in the detection of repeat expansions with short-read next-generation sequencing

Author:

Bahlo MelanieORCID,Bennett Mark F,Degorski Peter,Tankard Rick M,Delatycki Martin B,Lockhart Paul J

Abstract

Short tandem repeats (STRs), also known as microsatellites, are commonly defined as consisting of tandemly repeated nucleotide motifs of 2–6 base pairs in length. STRs appear throughout the human genome, and about 239,000 are documented in the Simple Repeats Track available from the UCSC (University of California, Santa Cruz) genome browser. STRs vary in size, producing highly polymorphic markers commonly used as genetic markers. A small fraction of STRs (about 30 loci) have been associated with human disease whereby one or both alleles exceed an STR-specific threshold in size, leading to disease. Detection of repeat expansions is currently performed with polymerase chain reaction–based assays or with Southern blots for large expansions. The tests are expensive and time-consuming and are not always conclusive, leading to lengthy diagnostic journeys for patients, potentially including missed diagnoses. The advent of whole exome and whole genome sequencing has identified the genetic cause of many genetic disorders; however, analysis pipelines are focused primarily on the detection of short nucleotide variations and short insertions and deletions (indels). Until recently, repeat expansions, with the exception of the smallest expansion (SCA6), were not detectable in next-generation short-read sequencing datasets and would have been ignored in most analyses. In the last two years, four analysis methods with accompanying software (ExpansionHunter, exSTRa, STRetch, and TREDPARSE) have been released. Although a comprehensive comparative analysis of the performance of these methods across all known repeat expansions is still lacking, it is clear that these methods are a valuable addition to any existing analysis pipeline. Here, we detail how to assess short-read data for evidence of expansions, reviewing all four methods and outlining their strengths and weaknesses. Implementation of these methods should lead to increased diagnostic yield of repeat expansion disorders for known STR loci and has the potential to detect novel repeat expansions.

Funder

Australian Government NHMRC IRIIS

Victorian Government’s Operational Infrastructure Support Program

NHMRC Senior Research Fellowship

NHMRC Program Grant

Publisher

F1000 Research Ltd

Subject

General Pharmacology, Toxicology and Pharmaceutics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

Cited by 81 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3