In Genome Research this week, researchers in Australia suggest a recombination hotspot leads to sequence variability within the novel gene AK005651 and could contribute to an individual's susceptibility to type 1 diabetes. Sequence analysis of a series of congenic non-obese diabetic mouse strains and in 25 inbred strains revealed several haplotypes, including a unique non-obese diabetic haplotype associated with varying levels of type 1 diabetes susceptibility, the researchers write. "Haplotype diversity within this interval between congenic NOD mouse strains was due to a recombination hotspot that generated four crossover breakpoints, including one with a complex conversion tract," they add. "The Idd11 haplotype and recombination hotspot are located within a predicted gene of unknown function, which exhibits decreased expression in relevant tissues of NOD mice."
Published in advance in Genome Research this week, researchers at McGill University determine the role of splicing polymorphisms in human gene expression. Using deep mRNA sequencing of two CEU individuals, the researchers identified a large number of genes that are differentially spliced between the two samples and associated many of those differences with nearby SNPs. "We find a significant enrichment of alternative splicing events within a set of highly confident [expression quantitative trait loci] targets discovered in previous studies, suggesting a role of AS in regulating overall gene expression levels," the researcher write.
Also published in advance in Genome Research this week, a team of researchers says interactome mapping could provide new mechanistic details underlying Alzheimer's disease. Alzheimer's disease genes are highly interconnected, the researchers speculate, allowing the researchers to set up an interaction discovery strategy to unveil novel Alzheimer's disease genes, including causative and susceptibility genes. Overall, they reported 200 high-confidence protein-protein interactions between eight confirmed Alzheimer's disease-related genes and 66 candidate genes. "Of these, 31 are located in chromosomal regions containing susceptibility loci related to the etiology of late-onset AD, and 17 show dysregulated expression patterns in AD patients, which makes them very good candidates for further functional studies," the researchers write.
An international team of researchers report epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer. The researchers conducted expression microarray analysis of 39 cell lines and 17 primary culture specimens grown in the presence or absence of DNA methyltransferase inhibitors. Induction of expression and standard deviation among untreated samples identified 378 candidate methylated genes, many of them relevant to TGF-beta signaling, the researchers write. "These data suggest that accumulation of age-related epigenetic modifications leads to suppression of TGF-beta signaling and contributes to ovarian carcinogenesis," they add.