Centre for Clinical and Nutritional Chemistry, School of Chemistry, University of The Punjab, Lahore, Pakistan.
Thompson Center for Autism & Neurodevelopment, University of Missouri, Columbia, MO, USA.
Ann Hum Biol. 2023 Feb;50(1):100-107. doi: 10.1080/03014460.2023.2180087.
Runs of homozygosity (ROHs) analysis of controls provide a convenient resource to minimize the association of false positive results of disease-associated ROHs and genetic variants for simple and complex disorders in individuals from the same population. Evidence for the value of ROHs to speech or language-related traits is restricted due to the absence of population-matched behaviourally defined controls and limited family-based studies.
This study aims to identify common ROHs in the Pakistani population, focussing on the total length and frequency of ROHs of variable sizes, shared ROHs, and their genomic distribution.
We performed homozygosity analysis (in PLINK) of 86 individuals (39 males, 47 females) with no history of speech or language-related phenotypes (controls) who had been genotyped with the Illumina Infinium QC Array-24.
ROHs of 1-<4 megabases (Mb) were frequent in unrelated individuals. We observed ROHs over 20 Mb among six individuals. Over 30 percent of the identified ROHs were shared among several individuals, indicating consanguinity's effect on the Pakistani population.
Our findings serve as a foundation for family-based genetic studies of consanguineous families with speech or language-related disorders to ultimately narrow the homozygosity regions of interest to identify pathogenic variants.
对对照个体进行纯合子区域（ROH）分析为来自同一人群的个体中简单和复杂疾病相关的 ROH 和遗传变异的假阳性结果提供了最小化关联的便利资源。由于缺乏与行为定义的对照相匹配的人群、以及有限的基于家系的研究，ROH 与言语或语言相关特征的相关性证据受到限制。
本研究旨在确定巴基斯坦人群中的常见 ROH，重点关注不同大小的 ROH 的总长度和频率、共享 ROH 及其基因组分布。
我们对 86 名（39 名男性，47 名女性）无言语或语言相关表型病史的个体（对照）进行了纯合子分析（在 PLINK 中），这些个体已经使用 Illumina Infinium QC Array-24 进行了基因分型。
无关个体中 1-<4 兆碱基（Mb）的 ROH 很常见。我们观察到六个个体中存在超过 20 Mb 的 ROH。超过 30%的鉴定 ROH 在几个个体之间共享，表明近亲繁殖对巴基斯坦人群的影响。
我们的发现为具有言语或语言相关障碍的近亲家庭的基于家系的遗传研究奠定了基础，最终缩小了关注的纯合区域，以鉴定致病性变异。
