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Genetic Dependence and Genetic Diseases

Li, B.; Bian, W.-J.; Zhou, P.; Wang, J.; Fan, C.-X.; Xu, H.-Q.; Yu, L.; He, N.; Shi, Y.-W.; Su, T.; Yi, Y.-H.; Liao, W.-P.

2023-08-05 genetics
10.1101/2023.08.02.551736 bioRxiv
Show abstract

The human life depends on the function of proteins that are encoded by about twenty-thousand genes. The gene-disease associations in majority genes are unknown and the mechanisms underlying pathogenicity of genes/variants and common diseases remain unclear. We studied how human life depends on the genes, i.e., the genetic-dependence, which was classified as genetic-dependent nature (GDN, vital consequence of abolishing a gene), genetic-dependent quantity (GDQ, quantitative genetic function required for normal life), and genetic-dependent stage (GDS, temporal expression pattern). Each gene differs in genetic-dependent features, which determines the gene-disease association extensively. The GDN is associated with the pathogenic potential/feature of genes and the strength of pathogenicity. The GDQ-damage relation determines the pathogenicity of variants and subsequently the pathogenic genotype, phenotype spectrum, and inheritance of variants. The GDS is mainly associated with the onset age/evolution/outcome and the nature of genetic disorders (disease/susceptibility). The varied and quantitative genetic-dependent feature of genome explains common mild phenotype/susceptibility. The genetic-dependence discloses the mechanisms underlying pathogenicity of gene/variants and common diseases. One sentence summaryGenetic dependent feature differs in genes and determines pathogenicity of genes/variants and the clinical features of genetic diseases.

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