In this week's Nature, a team led by researchers from Harvard Medical School and the Massachusetts Institute of Technology describes a machine learning-based method for precise and predictable CRISPR genome editing of pathogenic variants. The investigators built a library of roughly 2,000 Cas9 guide RNAs paired with DNA target sites and trained with a computer model called inDelphi. The model predicted that 5 to 11 percent of Cas9 guide RNAs targeting the human genome are "precise-50," yielding a single genotype comprising greater than or equal to 50 percent of all major editing products. The authors experimentally validated confirmed precise-50 insertions and deletions in 195 human disease-relevant alleles, establishing their approach for precise, template-free genome editing.
And in Nature Genetics, an international research team reports the whole-genome sequencing of 175 ethnic Mongolians representing six tribes, revealing strong population stratification among these tribes that correlates to the diverse demographic histories in the region. By incorporating their results into the 1000 Genomes Project panel, the scientists identify derived alleles shared between Finns and Mongolians/Siberians, "suggesting that substantial gene flow between northern Eurasian populations has occurred in the past," they write. "Furthermore, we highlight that North, East, and Southeast Asian populations are more aligned with each other than these groups are with South Asian and Oceanian populations." GenomeWeb has more on this study, here.
And in Nature Plants, a group of Canadian and French investigators presents the whole-genome landscape of symbiotic genes of Medicago truncatula A17, a legume model species notable for endosymbiosis studies. Among their findings are 1,037 upregulated long non-coding RNAs involved in symbiotic nodule development, as well as clusters of significant numbers of genes upregulated in nodules or expressed in the nodule differentiation zone. These so-called symbiotic islands, the scientists discover, contain numerous expressed lncRNA genes and display differentially both DNA methylation and histone marks.