Relationship between Mutant Genes, SNPs and Mutation Types in Children with Hyperthyroidism Based on Canonical correlation Analysis (Preprint)

Abstract

BACKGROUND Generally, different mutation types affect patients to various degrees. Some mutation types, such as synonymous mutations, do not cause changes in amino acid sequence and have little impact on patients. In contrast, some types of mutations will lead to wrong encoding or stop encoding of amino acid sequences, which will have a more significant impact on patients. OBJECTIVE Therefore, this paper intends to find the genetic characteristics of hyperthyroidism in children from the perspective of mutation types: missense mutations, synonymous mutations, nonsense mutations, and splice site mutations, and explore the relationship between mutant Genes, SNPs, and mutation types in patients. Finally, find the mutation type in which the specific mutant gene and the mutation site were biased. METHODS Use the canonical correlation analysis method to find the relationship between the mutant gene, the mutation site, and the mutation type. RESULTS Based on the complete linear correlation, single value, and Pearson correlation coefficient, screen the mutant genes and SNPs, then get 23 representative mutant genes from 144 mutant genes in 39 children and 8 representative SNPs from 1221 SNPs in 39 children. Canonical variables were constructed using data from representative mutant genes, SNPs, and their corresponding mutation types for canonical correlation analysis. A significant positive correlation between the mutant gene and the mutation type and a significant positive correlation between SNPs and the mutation type were found through canonical variable correlation and significance tests.The mutant genes for children with hyperthyroidism consist of 23 representative mutant genes, among which the genes ACADM, ATM, BARD1, CALCA, CAPN3, CRP, DNMT1, DNMT3A, FANCC, GHRL, KANK1, LRSAM1, TPO, TSHR, VWF are all prone to missense mutations, nonsense mutation, and synonymous mutation, the gene CGA is prone to splice site mutation. Among the 23 genes, the gene KANK1 has the greatest impact on the ensemble of mutant genes. SNPs for children with hyperthyroidism consist of 8 representative SNPs, among which g.1529224C>T, g.23019637C>G and g.44651599T>C are prone to missense mutations, g.1533961C>T, g.12718004G> A, g.43082453A>G, g.44652143G>A and g.71809992C>T are prone to synonymous mutations. The site g.44651599T>C has the greatest impact on the ensemble of SNPs. CONCLUSIONS There is a strong correlation between gene mutation types and mutant genes and between mutation types and SNPs in children with hyperthyroidism. Each mutant gene and SNP has a more preferred mutation type, among which gene CGA and gene KANK1 may be the mutant gene that has the most significant impact on children, and SNP g.44651599T>C may be the SNP that has the greatest impact on children.