In this week's Science, a team of researchers from across the UK publishes a study demonstrating just how much the human genome can compensate for a loss of protein-coding genes. They sequenced the genomes of 3,222 adults of Pakistani descent who had a high level of parental relatedness, which results in a large number of identical gene sets in genomes. An analysis revealed a total loss of function for 781 different protein-coding genes in 821 individuals. Notably, 38 individuals had homozygous loss-of-function genotypes associated with recessive diseases, yet their health profiles did not differ substantially from heterozygous controls, suggesting the existence of genomic mechanisms that can compensate for missing genes the encode critical proteins. GenomeWeb has more on this study here.
And in Science Translational Medicine, a University of Cambridge-led research group reports the first inherited mutation of SRC — the first cancer gene discovered — that causes a rare bleeding disorder in humans that cannot be fully reversed even by targeting the gene. The investigators studied a family with a severe bleeding disorder and found a dominant gain-of-function mutation in SRC that enhanced the gene's activity, leading to abnormal platelets and megakaryocytes. In vitro and in zebrafish, the mutation's effects could not be reversed entirely by inhibiting the gene. The findings shed new light onto a SRC's role in this rare bleeding disorder, and also offer a possible explanation to the severe bleeding observed in cancer patients treated with Src family kinases, or SFK, inhibitors. GenomeWeb also covers this here.