Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes

Genome Biology
Hui HuangKim Fechtel

Abstract

Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change. Human disease genes are unevenly distributed among human chromosomes and are highly represented (99.5%) among human-rodent ortholog sets. Differences are revealed in evolutionary conservation and selection between different categories of human disease genes. Although selection appears not to have greatly discriminated between disease and non-disease genes, synonymous substitution rates are significantly higher for disease genes. In neurological and malformation syndrome disease systems, associated genes have evolved slowly whereas genes of the immune, hematological and pulmonary disease systems have changed more rapidly. Amino-acid substitutions associated with human inherited dis...Continue Reading

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Methods Mentioned

BETA
transgenic

Software Mentioned

CLUSTALW
Ensembl
CoMet
OmniViz
BLAT
INPARANOID
BLAST
BLAST2
PAML
LocusLink

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