Volume 52 Issue 5, May 2020

Genetic discrimination is one of the most pervasive challenges resulting from research and development in human genetics. To collaboratively study and prevent this ethical issue, we established an international Genetic Discrimination Observatory comprising a network of researchers and stakeholders from more than 19 jurisdictions.

A new study identifies sorbitol dehydrogenase (SORD) deficiency as a slowly progressive hereditary motor axonopathy caused by a genetic defect in the second step of the polyol pathway, thus leading to elevated tissue and blood sorbitol. SORD deficiency is the most common recessive cause of neuropathy, for which therapeutic intervention with aldose reductase inhibitors may have potential.

A new study addresses whether transcription of enhancers and the resulting enhancer RNAs (eRNAs) play a role in mediating long-range interactions between enhancers and promoters. Studying the immunoglobulin heavy chain (Igh) locus, the authors find that transcription of the enhancers per se is required to establish but not maintain these interactions, and this mechanism may apply to a subset of other enhancer–promoter interactions.

Biallelic mutations in the sorbitol dehydrogenase gene SORD are identified as a common cause of hereditary neuropathy. Functional studies suggest that SORD deficiency may be treatable with aldose reductase inhibitors.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.

Depletion of RNA polymerase II pausing and elongation factor Spt5 in B cells indicates that ~50% of enhancer–gene pairs show co-regulated transcription. CRISPRa-mediated rescue of enhancer transcription in Spt5-depleted cells restores Igh gene expression.

Assembly of the first Gossypium herbaceum genome and improved Gossypium arboreum and Gossypium hirsutum genomes provide insights into the phylogenetic relationships and origin history of cotton A-genomes.

Sequencing and genomic diversification of five allopolyploid cotton species provide insights into polyploid genome evolution and epigenetic landscapes for cotton improvement.

Application of a new k-mer-based genome-wide association approach to 2,000 phenotypes in Arabidopsis thaliana, tomato and maize detects new associations with structural variants and with regions missing from reference genomes.

A new association method using both case–control status and family history (LT-FH) greatly increases association power in analyses of 12 diseases from the UK Biobank.