Using array comparative genomic hybridization data for 21,470 individuals, Baylor College of Medicine's James Lupski and colleagues considered the frequency with which deletions or other disruptive copy number variants appear in genes known for roles in recessive disease. As they report in Genome Research, the investigators unearthed more than 3,200 instances in which deletions affected one allele of a recessive disease gene, affecting 419 different recessive disease genes in all. The CNVs — which render individuals potential carriers of recessive disease — tended to occur in long genes and genes falling far from those contributing to dominant disease risk, study authors note. Based on their findings, they argue that "a complete recessive carrier screening method or diagnostic test should detect CNV alleles."
Pancreatic beta cells — insulin-secreting cells best known for their role in type 1 and type 2 diabetes — share certain expression profiles with neurons, another Genome Research study finds. A Swiss team assessed beta cell transcriptomics through deep RNA sequencing on purified beta cells from 11 individuals. Analysis of the sequences, which included comparisons with neighboring islet cells, helped the group unearth expression and splicing signatures distinct to beta cells as well as variants suspected of regulating beta cell expression patterns. Consistent with past reports, the study's authors saw that at least some genes showing enhanced expression in pancreatic beta cells overlapped with those believed to contribute to neuronal activity.
A Vanderbilt University-led group describes genetic changes to EGFR mutant lung cancers that may help render the cancers resistant to tyrosine kinase inhibitors that target EGFR alterations. By sequencing and comparing five drug-resistant EGFR mutated lung cancer cell lines and four sensitive lines, researchers uncovered known contributors to TKI treatment resistance, including MET gene amplifications or secondary mutations to the EGFR gene. They also saw several new variants — along with an over-representation of copy number changes — in the resistant lines. "These results demonstrate a framework for studying the evolution of drug-related genetic variants over time," the team writes, "and provide the first genome-wide spectrum of mutations associated with the development of cellular drug resistance in an oncogene-addicted cancer."