Volume 51 Issue 8, August 2019

Chromatin loops and domains are major organizational hallmarks of chromosomes. New work suggests, however, that these topological features of the genome are poor global predictors of gene activity, raising questions about their function.

Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

Long-read sequencing identifies a GGC repeat expansion in NOTCH2NLC that is associated with neuronal intranuclear inclusion disease, a progressive neurodegenerative disorder. The expansion results in abnormal anti-sense transcripts that could contribute to disease pathogenesis.

Whole-genome sequencing identifies noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and oculopharyngeal myopathy with leukoencephalopathy, three disorders with overlapping clinical features and neuroimaging findings.

Exome sequencing identifies loss-of-function CELA2A mutations in families with early-onset atherosclerosis and metabolic syndrome. Functional studies show that CELA2A is a circulating enzyme that reduces platelet activation, triggers insulin secretion and degradation, and increases insulin sensitivity.

The authors use theoretical justifications coupled with extensive simulations to accurately estimate SNP-heritability for 22 complex traits and diseases from the UK Biobank data, irrespective of the underlying genetic architecture of the trait.

An integrative three-dimensional genomic and transcriptional profiling of four human neural cell types links regulatory elements to their target genes and elucidates the function of noncoding variants in neuropsychiatric disorders.

Removal of boundary and intra-TAD CTCF-binding sites at the Sox9–Kcnj2 locus in mice leads to TAD fusion but no major changes in gene expression. Gene misexpression and disease phenotypes were obtained through inversions and/or repositioning of TAD boundaries.

Systematic analysis of highly rearranged balancer chromosomes in Drosophila shows that extensive changes to chromatin topology affect the expression of only a subset of genes.

Inactivation of DNA cross-link repair in mouse primordial germ cells makes them vulnerable to endogenously produced genotoxic aldehydes and leads to genetic instability.