纯合性的运行在欧洲人群中很常见，并且表明血缘关系，限制种群规模和隐性遗传特征。这里,我们在爱尔兰肌萎缩侧索硬化症（ALS）的病例对照队列中绘制纯合性（ROHs），一种毁灭性的神经系统疾病，具有高遗传性，但只有部分确定的遗传原因。我们比较了爱尔兰队列与大型英国队列的纯合性程度，并观察到爱尔兰人口中的ROHs比英国人更长，更频繁，ROHs的程度与爱尔兰岛内的人口因素相关。与人口匹配的对照相比，ALS病例中的ROHs也更长，更频繁，支持隐性遗传位点在ALS中起致病作用的假设。比较病例和对照之间的纯合单倍型揭示了ALS的几个潜在隐性风险位点，包括一个跨越ARHGEF1的基因组间隔，一个引人注目的ALS候选基因。
Runs of homozygosity are common in European populations and are indicative of consanguinity, restricted population size and recessively inherited traits. Here, we map runs of homozygosity (ROHs) in an Irish
case-control cohort for amyotrophic lateral sclerosis (ALS), a devastating neurological condition with high heritability yet only partially established genetic cause. We compare the extent of homozygosity in the Irish cohort with a large British cohort and observe that ROHs are longer and more frequent in the Irish population than in the British, and that extent of ROHs is correlated with demographic factors within the island of Ireland. ROHs are also longer and more frequent in ALS cases compared to population-matched controls, supporting the hypothesis that recessively inherited loci play a pathogenic role in ALS. Comparing homozygous haplotypes between cases and controls reveals several potential recessive risk loci for ALS, including a genomic interval spanning ARHGEF1, a compelling ALS candidate gene.
