In a Nature paper published online in advance this week, members of the 1,000 Genomes Project consortium report a map of unbalanced structural variants based on data from 185 whole human genome sequences. "Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications," the team writes. In its subsequent genotyping investigations, the team found "a depletion of gene disruptions amongst high frequency deletions." Further, in analyzing differential "size spectra of SVs originating from distinct formation mechanisms," the 1,000 Genomes Project team also "constructed a map of SV hotspots formed by common mechanisms."
Researchers at the Mayo Clinic and Washington University in St. Louis show in a Nature advance online publication that the histone methyltransferase MMSET, which is also known as NSD2 or WHSC1, "regulates histone H4K20 methylation and 53BP1 [p53-binding protein 1] accumulation at DNA damage sites" in mammals through a mechanism that requires the γH2AX-MDC1 pathway.
A team led by investigators at the Dana-Farber Cancer Institute demonstrates that SMAD4 is a "key regulator of PCA [prostate cancer] progression in mice and humans." In Pten-null mouse models, the team found "robust activation of the TGFβ/BMP–SMAD4 signaling axis" and the "emergence of invasive, metastatic and lethal prostate cancers with 100 percent penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate." By combining pathological and functional data for SMAD4, along with that from cyclin D1, SPP1, and PTEN, the researchers found that the resulting "four-gene signature ... is prognostic of prostate-specific antigen biochemical recurrence and lethal metastasis in human PCA," they write in Nature this week.
Investigators at the Salk Institute for Biological Studies and their collaborators report methylome profiles for five human iPSC lines as well as those for embryonic stem cells, somatic cell, and differentiated iPSCs, which show that iPSCs are subject to "significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation." They also show that the differentiation of iPSCs into trophoblasts incurs CG methylation reprogramming errors are "transmitted at high frequency."