Abdulaziz International School, Riyadh, Saudi Arabia.
Am J Med Genet A. 2023 Aug;191(8):2142-2148. doi: 10.1002/ajmg.a.63301. Epub 2023 May 23.
Consanguineous populations have a higher frequency of autosomal recessive diseases when compared to the rest of the world. This frequency is high enough that families in these populations may even have multiple autosomal recessive diseases. The recurrence risk calculation for the various combinations becomes increasingly more difficult as more recessive diseases are encountered in a family. Another challenge in these populations is investigating the pathogenicity of a variant by considering its segregation with the phenotype. Consanguinity causes the appearance of many homozygous variants due to the identity by descent phenomenon. As the number of these variants increases, so does the percentage of novel variants that need to be classified using segregation. Furthermore, the complexity of calculating the segregation power increases with the level of inbreeding, and in the case of consanguineous families, their pedigrees tend to be very complex. With the aim of addressing these two challenges using a mathematical algorithm, ConsCal, a tool made to specifically cater to medical genetics professionals working with consanguineous populations, was developed. The user-friendly tool contains two primary functions. It simplifies recurrence risk calculations for any combination of autosomal recessive diseases and analyzes familial segregation data to assign a numerical value to the segregation power of a given variant to aid in its classification. As the use of genomics becomes more widespread, this tool can help address the growing need in calculating recurrence risk and segregation power in consanguineous populations.
与世界其他地区相比，血缘人群的常染色体隐性疾病频率更高。这种频率足够高，以至于这些人群中的家庭甚至可能有多例常染色体隐性疾病。随着家庭中遇到的隐性疾病越来越多，各种组合的复发风险计算变得越来越困难。在这些人群中，另一个挑战是通过考虑其与表型的分离来研究变异的致病性。由于同源性下降现象，血缘关系导致许多纯合变体的出现。随着这些变体数量的增加，需要使用分离来分类的新变体的百分比也在增加。此外，随着近亲繁殖程度的增加，分离能力的计算复杂性也会增加，而在血缘家庭中，他们的家谱往往非常复杂。为了使用数学算法解决这两个挑战，开发了 ConsCal 工具，这是一种专门为与血缘人群合作的医学遗传学专业人员设计的工具。该用户友好的工具包含两个主要功能。它简化了任何常染色体隐性疾病组合的复发风险计算，并分析家族分离数据，为给定变体的分离能力分配一个数值，以帮助对其进行分类。随着基因组学的应用越来越广泛，该工具可以帮助满足计算血缘人群中复发风险和分离能力的日益增长的需求。
