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This Week in Nature: Mar 7, 2019

In Nature Biotechnology this week, a Seoul National University team reports a new CRISPR-based method for assessing the genome-wide target specificity of adenine base editors. The scientists created a modified version of Digenome-seq — an in vitro whole-genome sequencing method for identifying CRISPR-induced double-strand breaks — that could detect adenine base editor off-target sites with a substitution frequency of 0.1 percent or more, they write. The authors also use targeted sequencing to show that use of pre-assembled adenine base editor ribonucleoproteins, modified guide RNAs, and the Cas9 variant Sniper/Cas9 reduces adenine base editor off-target activity in human cells. GenomeWeb has more on this and a related study, here.

Also in Nature Biotechnology, scientists from Syngenta Crop Protection and collaborators describe the use of haploid induction (HI) — a method for generating double haploid plants in one or two generations — for genome editing in commercial crops. The technique uses the aberrant reproductive process of HI to induce edits in nascent seeds of a range of monocot and dicot species, the researchers state. Since edited haploid plants lack both the haploid-inducer parental DNA and the editing machinery, they "could be used in trait testing and directly integrated into commercial variety development."

And in Nature Medicine, a group of French and US scientists publishes a study using genome sequencing to identify potential new targets for spitzoid melanoma — which commonly affects children and adolescents, and frequently lacks an established genetic driver — and other forms of the cancer. Clinical whole-genome and transcriptome sequencing of a spitzoid tumor from an adolescent revealed a novel gene fusion of MAP3K8, encoding a serine-threonine kinase that activates MEK, while treatment of an MEK inhibitor produced a transient response. Further analysis of additional spitzoid tumors uncovered in-frame fusions or C-terminal truncations of MAP3K8 in 33 percent of cases, while data mining of RNA-seq from the Cancer Genome Atlas showed analogous MAP3K8 rearrangements in 1.5 percent of adult melanomas. "Our analysis of a single index case highlights the value of comprehensive sequencing in identifying previously undescribed somatic alterations that can impact treatment," the scientists write.

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.