October 23, 2009
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A lucky find and two very different genomics projects…
Connective Tissue Disorder Linked to Defects in Ltbp4: A McGill University researcher collaborating on two independent projects, one from Washington University School of Medicine and the other from New York University School of Medicine, made the coincidental link between the two after realizing that the tissue defects were identical. Dr. Elaine Davis, an electron microscopy expert at McGill, analyzed tissue from children born with abnormally developed lungs, gastrointestinal and urinary systems, skin, skull, bones and muscles. The underlying cause is a connective tissue disorder called cutis laxa that also causes skin to hang loosely from the body. At the same time, Dr. Davis was analyzing tissue taken from Ltbp4 gene knockout mice from New York University when she realized that the connective tissue defects in the human and mouse samples were identical. This connection was confirmed when they sequenced the Ltbp4 gene in human patients and discovered recessive mutations. With this discovery, they now have a molecular target to understand the disease and to design therapeutic strategies. The study is reported in The American Journal of Human Genetics.
A Deep-sea Microbe Genome: The microbe, SUP05, lives in the deep ocean “dead zone” where oxygenated water is minimal. It survives by using other compounds instead of oxygen, such as nitrates, sulphates and metals. A recent surge in population suggests an expanding low-oxygen ocean ecosystem and is an indicator of global climate change. University of British Columbia professor Dr. Steve Hallam and his research group analyzed the entire genome of SUP05 and identified a number of genes mediating carbon assimilation, sulfur oxidation, and nitrate respiration. This study provides the first insight into the metabolism of these microbes and their effects on nutrients and gases in the deep-ocean ecosystem and will also lead to further understanding of their ecological and biogeochemical role. The report appears in this week’s edition of Science.
Allelic Expression Genomic Map: Illumina genomics technology was used in this study to map global allelic expression differences associated with cis-acting variants. Cis-acting elements can affect gene expression and variations due to single nucleotide polymorphisms (SNPs) explain a large percentage of the phenotypic differences in the population. It is very informative to have this global map of the cis-acting variants and helps researchers identify variants associated with diseases. To demonstrate this, they finely mapped cis-regulatory SNPs in a region in chromosome 8 associated with lupus. The study was performed by Dr. Tomi Pastinen and his Genome Quebec team at McGill University and the report was published in Nature Genetics.
DNA Repair Suppresses c-Myc Lymphoma: Overexpression of c-Myc in B cells is associated with lymphomas but requires secondary mutation events for the disease to develop. In this study, immunologist Dr. Alberto Martin and his research team at the University of Toronto identified that the DNA repair protein, Msh2, plays an important role in mitigating c-Myc associated cancer. To demonstrate this, they generated mice that overexpress c-Myc but with Msh2 mutations such that they are deficient in DNA mismatch repair. These mice rapidly develop B cell lymphomas, which suggests that Msh2-dependent DNA repair actively suppresses c-Myc associated oncogenesis. The report appears in the early edition of The Proceedings of the National Academy of Sciences.