目的:对视网膜信息网络(RetNet)数据库中所有基因的紊乱程度进行全面审查,与遗传性视网膜疾病(IRD)有关。评估了它们与错义变异的关联。
方法:本研究包括来自RetNet的IRD基因。基因组聚集数据库(gnomAD)上的公开可用数据用于分析总和致病性错义变异的数量。Metapredict,一个准确和高性能的预测器,再现共识障碍分数,被用来计算无序。
方法:主要结局指标是疾病百分比,致病性百分比,总错义变体的数量,以及总错觉变化的百分比。
结果:我们纳入了287个RetNet基因,相关数据来自gnomAD。平均疾病百分比为26.3%±26.0%,平均致病性百分比为5.2%±11.0%,平均错义变异总数为424.4±450.0,平均错义百分比为50.0%±13.4%.疾病百分比遵循双峰分布,在0至10个疾病十分位数中发生次数最高。鉴定了第一个疾病十分位数中的五个异常蛋白,其总错义变异数高于预期(HMCN1,ADGRV,USH2A,DYNC2H1、LAMA1和SLC38A8)。当排除时,%总错觉与疾病百分比显著相关(R=0.238,p=0.0240)。
结论:这项新的研究检查了与IRD有关的所有基因,发现大多数基因在0到10分位数有疾病,并且对错义变异相对不耐受。当解释未确定的重要性和错义变体的变体时,这可能具有未来的实用性。
A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated.
IRD genes from RetNet were included in this study. Publicly available data on the genome aggregation database (gnomAD) were used to analyze the number of total and pathogenic missense variants. Metapredict, an accurate and high-performance predictor that reproduces consensus disorder scores, was used to calculate disorder.
The main outcome measures were percent disorder, percent pathogenicity, number of total missense variants, and percent total missense variation.
We included 287 RetNet genes with relevant data available from gnomAD. Mean percent disorder was 26.3% ± 26.0%, mean percent pathogenicity was 5.2% ± 11.0%, mean number of total missense variants was 424.4 ± 450.0, and mean percent total missense was 50.0% ± 13.4%. The percent disorder followed a bimodal distribution with the highest number of occurrences in the 0 to 10th disorder decile. The five outlier proteins in the first disorder decile with a higher-than-expected number of total missense variation were identified (HMCN1, ADGRV, USH2A, DYNC2H1, LAMA1, and SLC38A8). When excluded, % total missense was significantly associated with percent disorder (R = 0.238 and p = 0.0240).
This novel study examining all genes implicated in IRDs found that the majority genes had a disorder in the 0 to 10th decile and were relatively intolerant to missense variation. This may have future utility when interpreting variants of undetermined significance and missense variants.