Quantifying the contribution of recessive coding variation to developmental disorders
We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.
A DNA methylation reader complex that enhances gene transcription
DNA methylation generally functions as a repressive transcriptional signal, but it is also known to activate gene expression. In either case, the downstream factors remain largely unknown. By using comparative interactomics, we isolated proteins in Arabidopsis thaliana that associate with methylated DNA. Two SU(VAR)3-9 homologs, the transcriptional antisilencing factor SUVH1, and SUVH3, were among the methyl reader candidates.
Semiconducting polymer blends that exhibit stable charge transport at high temperatures
Although high-temperature operation (i.e., beyond 150°C) is of great interest for many electronics applications, achieving stable carrier mobilities for organic semiconductors at elevated temperatures is fundamentally challenging. We report a general strategy to make thermally stable high-temperature semiconducting polymer blends, composed of interpenetrating semicrystalline conjugated polymers and high glass-transition temperature insulating matrices.
Building two-dimensional materials one row at a time: Avoiding the nucleation barrier
Assembly of two-dimensional (2D) molecular arrays on surfaces produces a wide range of architectural motifs exhibiting unique properties, but little attention has been given to the mechanism by which they nucleate. Using peptides selected for their binding affinity to molybdenum disulfide, we investigated nucleation of 2D arrays by molecularly resolved in situ atomic force microscopy and compared our results to molecular dynamics simulations.