NEW YORK (GenomeWeb News) – In an American Journal of Human Genetics paper, researchers from David Goldstein's Duke University lab and elsewhere continue to make a case for the importance of rare variants in human disease. From their analyses of genome sequence data for 29 individuals of European descent who were sequenced with the Illumina GAII, they found that rare variants are more likely than common variants to fall in protein-coding and regulatory parts of the human genome — a pattern that they chock up to selection against rare, deleterious genetic changes.
"The more common a variant is, the less likely it is to be found in a functional region of the genome," Goldstein said in a statement. "Scientists have reported this observation before, but this study is the most comprehensive effort to date using annotations of the functional regions of the human genome and fully sequenced genomes."
An exome sequencing study by Australian researchers in PLoS Genetics has uncovered a glitch in the RNase mitochondrial RNA processing complex gene POP1 that can lead to a form of dwarfism called anauxetic dysplasia. The team used Nimblegen SeqCap EZ exome capture methods combined with Illumina GAII paired-end sequencing to re-sequence the whole exomes of four individuals from an affected family in which no family members carried mutations in the most well known anauxetic dysplasia gene. In the process, the researchers found loss-of-function mutations in POP1 in two daughters with skeletal dysplasia that were not found in their unaffected parents.
In PLoS ONE, researchers from the Massachusetts General Hospital, Stanford University, and the California-based information tech company CollabRx describe their molecular subtype scheme for classifying melanoma. Rather than categorizing the skin cancer by conventional histological methods, their Melanoma Molecular Disease Model, or MMDM, classification system relies on genetic mutation, pathway, and clinical information available through a curated, online site. The MMDM resource is an initiative by Cancer Commons, a personalized cancer treatment project spearheaded by CollabRx for melanoma and other types of cancer.
"Recent developments in our understanding of the molecular drivers of this disease have led to a new generation of targeted therapies that are proving effective in patients whose tumors harbor certain genetic defects," co-author Keith Flaherty, co-chief editor of Cancer Commons Melanoma and developmental therapeutics director at Massachusetts General Hospital, said in a statement. "Rather than treating melanoma as a single disease, it makes sense to stratify tumors into molecular subtypes and treat each with the most appropriate therapies."
Louisiana State University researchers reported in the Proceedings of the National Academy of Sciences that they have used comparative transcriptomics to get new clues about how Atlantic killifish populations adapt to environments with a broad range of salt concentrations. They used microarrays to assess genotype and gene expression profiles in dozens of fish from individual sites along the Potomac River, James River, and Chesapeake Bay that ranged from freshwater to brackish and saltwater. Their findings hint that non-neutral divergence patterns are particularly common in genes with apparent roles in the physiological adaptations to freshwater and brackish water. And, they say, "It is not the well-known effectors of osmotic acclimation, but rather the lesser-known immediate-early responses, that appear important in contributing to population differences."
Genomics In The Journals is a new weekly feature pointing readers to select, recently published articles involving genomics and related research.