In this week's Nature, a Broad Institute team reports the development of a new class of base editors that enable the replacement of all four bases of DNA selectively and with high efficiency — and without the need for double-stranded DNA breaks. Previously, the scientists developed a system related to CRISPR-Cas9 that could target and modify single bases, but were only able to convert G-C base pairs to T-A base pairs. In their latest study, the group describes a new class of adenine base editors (ABEs) that enable A-T base pairs to be converted to G-C base pairs. "Together with our previous base editors, ABEs advance genome editing by enabling the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage," they write. GenomeWeb has more on this and a related study, here.
Also in Nature, an international research team describes the identification of new breast cancer risk loci. The team performed a genome-wide association study of the disease in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. They uncovered 65 new risk loci associated with overall breast cancer risk, which they say account for 18 percent of the familial relative risk for the disease.
Meanwhile in Nature Genetics, a multi-institute team reports finding new genetic variants associated with the risk of estrogen receptor (ER)-negative breast cancer. The investigators performed a genome-wide association study using 21,468 ER-negative cases and 100,594 controls, combined with 18,908 BRCA1 mutation carriers — 9,414 of whom had breast cancer — all of European origin. They found 10 new loci linked to ER-negative breast cancer risk, which, when previously reported loci are factored in, account for 16 percent of the familial risk for this type of breast cancer.
GenomeWeb also covers the previous two studies, here.
And in Nature Communications, a Johns Hopkins-led research group details the identification of epigenetic factors that influence the development of autism spectrum disorder (ASD). By combining datasets of genetic and epigenetic data collected from different sources such as cord blood, peripheral blood, and brain samples, the investigators uncovered epigenetic changes that associate with previously identified ASD genes. Notably, the study found significant overlap between findings obtained peripheral blood epigenetic data and from brain samples. "Our work suggests that genetic and epigenetic data integration, from a variety of tissues, will continue to provide ASD-related functional insights," the researchers write.