In PLoS Genetics this week, Duke University School of Medicine's David Goldstein and his colleagues depict their analysis of 20 human genomes. The team sequenced 10 genomes from individuals with severe hemophilia A and 10 control genomes, and "provide a proof of concept for the identification of rare and highly penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set." In addition, Goldstein's team also found that the number of novel single-nucleotide variants discovered per genome "seems to stabilize at about 144,000" and that "on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways," they write.
Also in PLoS Genetics this week, a research team led by investigators at the Broad Institute details "accurately assessing the risk of schizophrenia conferred by rare copy number variation affecting genes with brain function." In particular, they note the impact of confounders; they genotype rare CNV events in 2,415 unaffected controls, and "applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set," they write. The team proposes a cnv-enrichment test to compare cases and controls (in place of the standard pathway traditionally applied to this task). The researchers validated the cnv-enrichment test using data from the International Schizophrenia Consortium.
David Bowtell at the Peter MacCallum Cancer Centre in East Melbourne, Australia, and his colleagues report in PLoS One this week on novel interactions between genomic loci in ovarian cancer, which they've identified via copy number analysis of data from 398 tumors. "The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11," the authors write. In interrogating genomic stability, Bowtell et al. also "found a correlation of the number of higher amplitude gains with poorer overall survival."
In another paper appearing in PLoS One, investigators in the UK show that "reduced expression of IFIH1 is protective for type 1 diabetes." In their allele-specific expression interrogations, the team found that "the T1D protective haplotype correlates with reduced IFIH1 transcription in interferon-β stimulated peripheral blood mononuclear cells." Then, using multiflow cytometry and qPCR, the team found "reduced expression of IFIH1 in individuals heterozygous for three of the T1D-associated rare alleles," according to the paper.