Researchers from Illumina, the University Medical Center Utrecht, and elsewhere describe a computational approach for detecting short tandem repeat expansions from short read genome sequence data generated without PCR amplification. The team applied its algorithm, known as ExpansionHunter, to genome sequence data for almost 2,800 control individuals and 3,001 individuals with amyotrophic lateral sclerosis — one of the conditions that can arise from rampant short tandem repeat expansion. Of the 212 cases with known C9orf72 expansions, the ExpansionHunter software classified 208 as expansions and four as potential expansions. All but three unaffected controls were placed in the wild-type category. The authors subsequently applied the approach to genome sequences from 152 additional individuals with repeat expansion-related conditions such as Fragile X syndrome or Huntington's disease.
A UK team takes a look at structural mosaicism using an approach dubbed MrMosaic, which picks up such mosaic structural changes from exome or whole-genome sequence data with the help of read coverage and allele fraction shifts. When they applied MrMosaic to exome sequences for 4,911 individuals with undiagnosed developmental conditions, for example, the researchers detected 11 structural mosaic events in nine of the individuals, including mosaic events that turned up in saliva samples, but could not be detected in corresponding blood samples. "Additional work is required to investigate for which developmental disorders tissue-limited mosaicism is common," they write, noting that "availability of more sensitive detection methods will improve the detection of a larger fraction of events limited to a single tissue."
University of Maryland, Emory University, and University of Michigan investigators provide information on a Mobile Element Locator Tool (MELT) that they came up with to track down mobile element insertion structural variants in the human genome and human populations. After establishing MELT as part of the 1000 Genomes Project, the team used it to find mobile element insertions in more than 2,500 low-coverage genome sequences and 30 high-coverage genomes from 1000GP, along with chimpanzee, Neanderthal, and Denisovan genomes. "[O]ur study provides the most comprehensive map of [mobile element insertions] to date spanning chimpanzees, ancient hominids, and modern humans," the authors write, "and reveals new aspects of [mobile element insertions] in these lineages."