Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Genet Med. 2010 Apr;12(4):236-9. doi: 10.1097/GIM.0b013e3181ceb95d.
Consanguinity increases the coefficient of inbreeding, which increases the likelihood of presence of pathogenic mutations in a homoallelic state. Although this is known to have an adverse outcome by increasing the risk of autosomal recessive disorders, this very phenomenon has also made homozygosity mapping the most robust gene discovery strategy in the recent history of human genetics. However, homozygosity mapping can also serve as an extremely powerful tool in the clinical genetics setting as well. In particular, this method is highly suited in the setting of genetically heterogeneous conditions and inborn errors of metabolism that require sophisticated biochemical testing that may not be readily available. This article is meant to highlight the clinical utility of this strategy using illustrative clinical examples from the author's own clinical genetics practice.
血缘关系会增加近交系数，从而增加同型等位基因中致病突变的存在可能性。虽然这种情况会增加常染色体隐性疾病的风险，被认为是不利的，但这种现象也使得纯合子定位成为人类遗传学史上最强大的基因发现策略。然而，纯合子定位在临床遗传学领域也可以作为一个极其强大的工具。特别是在遗传异质性疾病和需要复杂生化检测但这些检测可能不易获得的先天性代谢错误的情况下，这种方法非常适用。本文旨在通过作者自己的临床遗传学实践中的临床实例来说明这种策略的临床实用性。
