Abstract

The “Mendelian code” hypothesis postulates a relationship between Mendelian (monogenic) and common pathologies. In this hypothesis, polymorphisms in the genes of Mendelian diseases may have a significant contribution to predisposition to common diseases in which the same biochemical pathways may be involved. In this review a group of genes encoding various proteins participating in the DNA repair, with a particular focus on the BRCA1-associated genome surveillance complex (BASC), is presented through the prism of the “Mendelian code” hypothesis. Here we discuss (1) their main functions in the repair of DNA double-strand breaks (ATM, MRE11, NBN, RAD50, BRCA1, and BLM) and mismatch repair (MSH2, MSH6, MLH1, PMS2, RF-C, and PCNA); (2) the mitochondrial involvement of these proteins; (3) the involvement of BASC proteins in the development of an adaptive immune response. For 13 out of 16 BASC protein encoding genes, mutations leading to monogenic diseases have already been described; for 11, there are associations with common diseases or individual biological processes. Patients with mutations in the genes of the BASC complex and patients with severe combined immunodeficiency share similar symptoms. Polymorphisms within DNA repair genes may play a role in the development of common diseases through the involvement of the immune response. The pleiotropic effects of these genes suggest their participation in the development of various conditions, both in health and pathology.

中文翻译：

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变异参与人类常见疾病发展过程中的编码BRCA1相关基因组监视复合体（BASC）的基因。

摘要

“孟德尔法则”假设假设孟德尔（单基因）与常见病理之间存在关系。在该假设中，孟德尔疾病基因的多态性可能对易患易感性的常见疾病有重要贡献。在这篇综述中，通过“孟德尔密码”假设的棱镜提出了一组编码各种蛋白质的基因，这些蛋白质参与DNA修复，特别着重于BRCA1相关的基因组监视复合体（BASC）。在这里，我们讨论（1）它们在修复DNA双链断裂（ATM，MRE11，NBN，RAD50，BRCA1和BLM）和错配修复（MSH2，MSH6，MLH1，PMS2，RF-C和PCNA）中的主要功能。 ）; （2）这些蛋白质的线粒体参与；（3）BASC蛋白参与适应性免疫应答的发展。对于16种BASC蛋白编码基因中的13种，已经描述了导致单基因疾病的突变；对于11，存在与常见疾病或个体生物学过程的关联。BASC复合体基因突变的患者和严重合并免疫缺陷的患者具有相似的症状。DNA修复基因内的多态性可能通过免疫应答的参与在常见疾病的发展中发挥作用。这些基因的多效作用表明它们参与了健康和病理学方面各种疾病的发展。与常见疾病或个体生物学过程有关。BASC复合体基因突变的患者和严重合并免疫缺陷的患者具有相似的症状。DNA修复基因内的多态性可能通过免疫应答的参与在常见疾病的发展中发挥作用。这些基因的多效作用表明它们参与了健康和病理学方面各种疾病的发展。与常见疾病或个体生物学过程有关。BASC复合体基因突变的患者和严重合并免疫缺陷的患者具有相似的症状。DNA修复基因内的多态性可能通过免疫应答的参与在常见疾病的发展中发挥作用。这些基因的多效作用表明它们参与了健康和病理学方面各种疾病的发展。