Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226 014, India.
J Genet. 2021;100.
India has a large heterogeneous population with its unique social and genetic characteristics. Tradition of marriage between specific caste groups have produced unique characteristics to the mutation spectrum of genetic disorders and may be a higher prevalence of autosomal recessive (AR) disorders in some communities. We observed that in many nonconsanguineous families with rare autosomal disorders, maternally and paternally inherited mutations are same, indicating common ancestor. In this era of genomic techniques, finding homozygous regions have become easy. It was seen that the patients with AR disorders, who were homozygous for the disease causing pathogenic / likely pathogenic variations, have large stretches (0.6-188 Mb) of homozygosity around the causative sequence variations. SNP microarray data of patients from consanguineous and nonconsanguineous families also showed that even patients from nonconsanguineous families had 3-49 Mb size regions of homozygosity. Long stretches of homozygosity around homozygous rare pathogenic variants in nonconsanguineous families with rare AR disorders supports the notion that these couples may have a common ancestor for more than six generations and the system of marriages between same groups. Hence, using the strategy of homozygosity by descent even in nonconsanguineous families can be fruitful in identifying the novel pathogenic variations and novel genes.
印度拥有庞大的异质人口，具有独特的社会和遗传特征。特定种姓群体之间通婚的传统，导致遗传疾病的突变谱具有独特的特征，某些社区可能存在更高的常染色体隐性（AR）疾病的发病率。我们观察到，在许多非近亲结婚的罕见常染色体疾病的家庭中，母系和父系遗传的突变是相同的，这表明存在共同的祖先。在基因组技术时代，寻找纯合区域变得更加容易。我们发现，AR 疾病患者的疾病致病/可能致病变异为纯合子，在致病序列变异周围存在大片段（0.6-188Mb）的纯合子。来自近亲结婚和非近亲结婚家庭的患者的 SNP 微阵列数据还表明，即使是非近亲结婚家庭的患者也存在 3-49Mb 大小的纯合子区域。在罕见 AR 疾病的非近亲结婚家庭中，围绕纯合罕见致病性变异的大片段纯合子支持这样一种观点，即这些夫妇可能有六个多代以上的共同祖先，以及同一种族之间的婚姻制度。因此，即使在非近亲结婚的家庭中，利用同源纯合的策略也可以有效地识别新的致病性变异和新的基因。
