Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
A University of Pennsylvania-led team takes a look at genetic and epigenetic variation in individuals with diabetic kidney disease for a paper slated to appear in PNAS this week. Starting with findings from their genome-wide methylome association study, which included 500 well-phenotyped individuals from the Chronic Renal Insufficiency cohort, the researchers focused on sites in the genome where specific methylation features coincided with genetic variants or gene expression patterns. Those loci, in turn, appeared to be functionally linked to processes such as kidney development, inflammation, and apoptosis. "The current integrative analysis highlighted that genetic variants influence methylation and expression levels of multiple genes [that] are known to play important roles in the immune system and inflammation," the authors report, noting that "genes associated with the clearance of apoptotic cells and complement pathways have been identified as the putative kidney disease risk genes."
Researchers in China and the US tally single nucleotide changes, deletions, duplications, aneuploidy, and other alterations arising spontaneously in diploid forms of Saccharomyces cerevisiae yeast. The team performed whole-genome sequencing on 93 yeast isolates that had been nabbed from diploid S. cerevisiae subcultures grown under stress-free conditions, uncovering more than 1,300 single-base changes or small indels as well as 1,215 mitotic recombinations and related loss-of-heterozygosity events. "Based on our results, we present a method of calculating the probability of [a loss-of-heterozygosity] event for individual SNPs located throughout the genome," the authors write. "We also identified several hotspots for chromosomal rearrangements (large deletions and duplications)."
Duke University Medical Center and University of North Carolina-Chapel Hill researchers spell out the details of a mosaic mouse reporter system designed to systematically detect somatic mutations — an approach they used to assess roles for specific genes in hematopoietic cell development and clonal hematopoiesis. The team's "mosaic analysis system with Cre or Tomato," or MASCOT, approach hinges on mouse strains with conditional reporter protein alleles designed to distinguish between wild type cells and those containing somatic mutations. "[T]he MASCOT method enables easy tracking and retrieving of mutant cells from different tissues at any point during lineage tracking for quantitative assessment of cell-intrinsic phenotypes," the authors write, calling it a "valuable tool to aid functional dissection of somatically acquired mutations in studies of development and disease."