Cold Spring Harbor Laboratory's Jonathan Sebat and his colleagues report in a Nature paper published online in advance that copy-number gains at 7q36.3 are significantly associated with schizophrenia risk. In a two-stage, genome-wide scan for rare copy-number variants related to the neuropsychiatric disorder, the CSHL-led team found microduplications with variable breakpoints no more than 89 kilobases upstream of VIPR2 in 0.35 percent of schizophrenia patients versus 0.03 percent of controls. They show that "VIPR2 transcription and cyclic-AMP signaling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3," and suggest that the VPAC2 receptor may be a useful target for anti-psychotic drug development.
A team led by investigators at the Salk Institute presents its generation of iPSCs from Hutchinson-Gilford progeria syndrome patient fibroblasts, which the researchers say recapitulate signs of premature aging, including "absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations" associated with the condition. "Specifically, directed differentiation of HGPS-iPSCs to [smooth muscle cells] leads to the appearance of premature senescence phenotypes associated with vascular aging," the Salk researchers and their collaborators write, adding that their iPSCs broaden the purview of in vitro studies on human premature aging pathogenesis and the physiology of vascular aging.
In a Nature Genetics advance online publication, researchers at Washington University in St. Louis and their colleagues report a draft sequence of the parasitic nematode Trichinella spiralis genome. The WashU-led team sequenced the T. spiralis genome, which contains an estimated 15,808 protein-coding genes, at approximately "35-fold coverage using whole-genome shotgun and hierarchical map-assisted sequencing," and found in its subsequent comparative analysis that there are intra-chromasomal rearrangements across the nematode phylum. "This genome sequence and the identified pan-phylum characteristics will contribute to genome evolution studies of Nematoda as well as strategies to combat global parasites of humans, food animals and crops," the authors write.
Also in Nature Genetics this week, an international team led by researchers at the Oklahoma Medical Research Foundation shows that a functional variant downstream of TNFAIP3 is associated with systemic lupus erythematosus. "By fine-mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE," the authors write.