At genome level, although most LoF mutations are neutral or deleterious, at least some of them are under positive selection, and could contribute to biodiversity and adaptation. Overall, we highlight the importance of natural LoF mutations as a robust strategy to understand biological questions in ...
The identification of domestication-related genes remains very arduous. In this study, we present a systematic analytical approach that harnesses two recent advances in genomics, whole-genome sequencing and prediction of loss-of-function (LOF) mutations, to greatly facilitate the assembly of an ...
A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset ...
We also find that nearly all computational variant effect predictors, even those based solely on sequence conservation, underperform on non-LOF mutations. However, we do show that non-LOF mutations could potentially be identified by their tendency to cluster in three-dimensional space. Overall, our...
S17 X LOSS OF FUNCTION (LOF) MUTATION IN ANGIOPOIETIN LIKE 3 (ANGPTL3) IS ASSOCIATED WITH INCREASED PLASMA LIPOPROTEIN LIPASE ACTIVITY AND CHANGES IN LIPOPROTEIN COMPOSITION 来自 sapienza.pure.elsevier.com 喜欢 0 阅读量: 19 作者: I Minicocci,M Maranghi,M Arca,F Ceci,A Lahikainen,D Rader...
We show thatSLCO1B1LoF mutations significantly increase the risk of incident heart failure, thus implicating the metabolite in the causal pathway of disease. These results reveal new avenues into gene function and the understanding of disease etiology by integrating -omic technologies into a deeply ...
We searched the Human Gene Mutation Database (HGMD)27 and ClinVar28 for uORF-creating or uORF-disrupting variants, identifying 39 uAUG-creating and four stop-removing (likely) pathogenic/disease mutations in 37 different genes. All four stop-removing variants disrupt uORFs with uAUGs in a stro...
However, small insertions, deletions, indels, and splicing mutations in DSG2 have been also described. Presumably, these LoF mutations in DSG2 might induce nonsense-mediated mRNA decay and in consequence lead to loss of the adhesive function of the desmosomes as suggested by Kant et al. using ...
Gain-of-function mutation:A mutation that confers new or enhanced activity on a protein. Loss-of-function mutations, which are more common, result in reduced or abolished protein function. Loss of function and gain of function mutation | oncogenes and tumor suppressor genes ...
Secondly, we found an excess of LOF mutations in ASD candidate genes in our cases (p = 0.032). Overall, this suggests that carrying two damaging hits or LOF in previously identified candidate genes is a risk factor for ASD. This is similar to previous WES studies specifically identifying...