The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States.
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, United States.
Elife. 2017 Sep 12;6:e25060. doi: 10.7554/eLife.25060.
Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic Bio biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, , with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.
在疾病基因座的因果关系中建立信心是一项复杂的任务，通常需要来自统计遗传学和临床基因组学的支持数据。在这里，我们描述了一种结合使用的方法来识别和描述一种遗传疾病，该方法利用了医疗系统和人群规模映射中亲缘关系较远的患者。我们利用基因组数据在没有记录的家谱信息的情况下揭示了多民族生物库中遥远家谱的组成部分。通过与医疗记录的链接，我们发现了一个与遗传相关性升高和极端矮小都相关的基因座。我们将基因与一种以前被认为罕见且隐性的遗传疾病联系起来。我们证明，这种疾病在杂合子和纯合子中都有表现，表明一种常见的胶原蛋白疾病影响多达 2%的波多黎各血统个体，从而更好地理解复杂和孟德尔疾病的连续体。
