NEW YORK (GenomeWeb News) – In the online version of Nature, researchers from Australia, the US, and the UK describe how they used genome sequencing to find a melanoma-associated mutation in a gene that codes for a transcription factor regulating the production of the skin pigment melanin and more. The glutamic acid to lysine substitution in the MITF gene — detected in the genome of an individual from melanoma-affected Australian family and subsequently found in two more family members — seems to spur excess MITF activity by interfering with its sumoylation. The same variant was over-represented among individuals with melanoma in case-control and family-based samples from in Australia and the UK, investigators reported, and seems to contribute to both familial and sporadic forms of melanoma.
"These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility," co-senior author Kevin Brown, a researcher affiliated with the Translational Genomics Research Institute and the National Cancer Institute, and co-authors wrote.
Members of several large consortia teamed up to do a genome-wide association study of Kawasaki disease, a childhood condition characterized by systemic blood vessel inflammation disease that can lead to coronary artery damage and heart disease. The researchers included 2,173 individuals of European or Asian ancestry with Kawasaki disease and nearly 9,400 unaffected controls in the GWAS and replication phases of the study, appearing in Nature Genetics. The search led to a known Kawasaki disease risk locus with genome-wide significance on chromosome 19, as well as a previously unidentified genome-wide significant SNP in a chromosome 1 immunoglobulin G receptor gene called FCGR2A.
"The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease," the study's authors noted.
A BMC Genomics study by Danish researchers illustrates the information that can be gleaned by bringing together genome sequence, SNP, and copy number data. The team re-sequenced the genome of a Holstein Friesian bull and used genome sequence data and other analyses to characterize its genomic variation. They also compared the SNPs and structural variations that could be detected from sequence read data compared to those found using SNP arrays and comparative genomic hybridization arrays. In the bull genome, structural alterations were a larger source of variation than sequence changes, they reported, pointing to a "need to consider all types of variants when fine-mapping causal variants within trait-associated intervals."
The ability to resume normal gene expression patterns after temporary heat stress is a mark of thermal adaptation in the marine seagrass Zostera marina, according to a study in the early, online version of the Proceedings of the National Academy of Sciences. German researchers used transcriptome sequencing to gauge seagrass temperature adaptation and extreme temperature response in an effort to understand how climate change could impact the plant. When they compared the expression patterns in heat-stressed seagrass collected from sites in Northern Europe with those from Southern European locales, the team found that seagrass from both regions expressed similar genes during heat stress. But plants originating from warmer sites quickly returned to a pre-stress expression once the heat wave was over, while those from more northern climes did not.
"[T]he return of gene-expression patterns during recovery provides critical information on thermal adaptation in aquatic habitats under climatic stress," senior author Thorsten Reusch, an evolutionary ecology researcher at the Leibniz-Institute of Marine Sciences, and co-authors wrote. "As a unifying concept for ecological genomics, we propose transcriptomic resilience, analogous to ecological resilience, as an important measure to predict the tolerance of individuals and hence the fate of local populations in the face of global warming."
Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.