Structural analysis and pathogenicity prediction of novel discovered mutation sites of human RAG1 gene
10.3760/cma.j.cn101441-20220124-00038
- VernacularTitle:RAG1基因新发现变异位点的结构分析及致病性预测
- Author:
Yongxiang LIU
1
;
Yuwei DUAN
;
Zhiwei WENG
;
Shuting ZHANG
;
Xuerong LI
;
Xinliang PENG
;
Ruihong ZHOU
;
Shaohu ZHOU
Author Information
1. 广州中医药大学第一附属医院生殖医学科，广州 510405
- Publication Type:Journal Article
- Keywords:
Genes, RAG1;
Novel discovered mutation sites;
Bioinformatics;
Pathogenicity prediction
- From:
Chinese Journal of Reproduction and Contraception
2023;43(3):295-301
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the structure and function of recombination activating gene 1 (RAG1) related to severe combined immunodeficiency (SCID) before entering the preimplantation genetic testing for monogenic (PGT-M) cycle, and to predict the pathogenicity of its novel mutation sites.Methods:According to the whole exome sequencing reports of the probands in the Department of Reproductive Medicine, the First Affiliated Hospital of Sun Yat-sen University on August 2016, the chromosome karyotypes and Sanger sequencing of their parents from their peripheral blood, the structures and protein conserved domains of the novel mutation sites of RAG1 gene were analyzed by PROVEAN, PolyPhen-2 and Mutation Taster software, and the secondary and tertiary structures of the mutant and wild type RAG1 protein were reconstructed in three-dimensional structure to predict its pathogenicity. Results:The couple were carriers of RAG1 gene mutation, which were located on chromosome 11. The female was heterozygous missense mutation of c.946T>G (p.C316G) and the male was heterozygous integer mutation of c.1194_1196del (p.L399del). The amino acid of the RAG1 mutations mentioned above were highly conserved among human, chimpanzee, pig, cattle, rats and mice. The secondary and tertiary structure reconstruction showed that the RING-type zinc finger structure lost the ability to bind zinc ions due to c.946T>G mutation, and the deletion of leucine at position 399 caused by c.1194_1196del mutation reduced one hydrogen bond. Conclusion:It is speculated that the two novel mutation sites of RAG1 are pathogenic mutations, which expand the mutation spectrum of RAG1 gene and have important research value.
