In a paper published online in advance in Science this week, researchers at the Washington University School of Medicine report their use of whole-exome sequencing, followed by Sanger re-sequencing, to investigate 31 metastasizing uveal melanoma tumors, in which they identified inactivating somatic mutations in BAP1 on chromosome 3p21.1 in 26 — or 84 percent — of the samples. Among the mutations identified were 15 that are known to cause premature protein termination and six that affect the BRCA1-associated protein's ubiquitin carboxy-terminal hydrolase domains, the authors report. The team suggests that their data "implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target."
Also in Science Express this week, investigators participating in the International HIV Controllers Study show that "the major genetic determinants of HIV-1 control affect HLA class I peptide presentation." In their genome-wide association analysis in a diverse cohort of both HIV-1 controllers and progressors, the team found more than 300 SNPs within the major histocompatibility complex, "and none elsewhere." In addition, the researchers suggest that because specific amino acids in the HLA-B binding groove "explain the SNP associations," their "results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection."
A public-private collaboration among researchers at the University of California, San Francisco, and Life Technologies reports in this week's Science that the "evolution of yeast non-coding RNAs reveals an alternative mechanism for widespread intron loss." By analyzing small nucleolar RNA genes in Candida albicans via deep RNA sequencing and genome-wide splice junction annotations, the team found "extreme compaction and loss of associated exons, but retention of snoRNAs within introns." But, in their analysis of a Saccharomyces lineage, the UCSF-Life Tech team found that "introns … have been lost through widespread degeneration of splicing signals," which the researchers say may be "facilitated by innovations in snoRNA processing."
And in Science Translational Medicine this week, a team led by investigators at the University of California, Los Angeles, shows that common variants in CNTNAP2 are associated with frontal lobar connectivity, which the researchers say establishes a "mechanistic link between specific genetic risk for neurodevelopmental disorders and empirical data implicating dysfunction of long-range connections within the frontal lobe in autism." When considered along with supporting data from additional neuroimaging and cognitive-behavioral models of autism, the team suggests that "genetic variation at CNTNAP2 predisposes to diseases such as autism in part through modulation of frontal lobe connectivity."