蛋白截断变异(protein-truncating variant,PTV)通过引入终止密码子,移码突变或剪接位点,破坏蛋白编码基因[1]。蛋白截断变异的研究对于人类进化(human evolution),基因功能(gene function),疾病相关变异(disease-related variants)和疾病患者变异的临床解读(Clinical interpretation of variants in patients with disease)有着重...
We applied MAF filters to target rare variants: MAF < 0.001 in gnomAD (overall and every population except OTH) and leave-one-out MAF < 0.001 among our combined case and control test cohort. For variants to qualify, they had to also meet the following quality control filters: minimum ...
Protein-truncating variants inBSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver diseasedoi:10.1038/s41588-024-01694-xObesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed...
Protein-truncating variants can have profound effects on gene function and are critical for clinical genome interpretation and generating therapeutic hypotheses, but their relevance to medical phenotypes has not been systematically assessed. Here, we characterize the effect of 18,228 protein-truncating ...
蛋⽩截断变异（protein-truncatingvariant，PTV）蛋⽩截断变异（protein-truncating variant，PTV）通过引⼊终⽌密码⼦，移码突变或剪接位点，破坏蛋⽩编码基因[1]。蛋⽩截断变异的研究对于⼈类进化（human evolution），基因功能（gene function），疾病相关变异（disease-related variants）和疾病患者变异的临床...
A meta-analysis was then performed on protein-truncating variants (PTVs) identified in the studies for an association with breast cancer risk. A total of 10,209 publications were identified, of which 64 studies comprising a total of 25,418 cases and 52,322 controls in the 6 interrogated ...
555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48;P = 5.4 × 10−6). In meta-analyses with existing datasets...
Selective effects of heterozygous protein-truncating variants Brian Charlesworth William G. Hill Nature Genetics Correspondence 26 Nov 2018 Sections Figures References Abstract References Acknowledgements Author information Ethics declarations Integrated supplementary information Supplementary information Rights and ...
Supplementary Figure 3 Partitioning the rate ofde novovariants per exome on the basis of class 1, class 2, and pLI, by using the nonpsychiatric version of ExAC. Within each grouping, the rate is shown for ID/DD (left), ASD (middle), and unaffected ASD siblings (right) with the number...
and we only considered the alleles predicted to be high-confidence loss of function. As it is known that germlineBRCA2andBRCA1PTVs drive associations with cancer, we would expect most VAFs in these genes to be close to 50% in heterozygotes, whereas, for somatic variants, their VAFs would ...