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

摘要: mit the comprehensive investigation of rodent orthologs genes associated with human disease. Here, we investigate whether disease differ significantly from their respect to overall levels conservation and rates evolution- ary change Abstract Background: Model organisms have contributed substantially our understanding etiology as well having assisted development new treatment modalities. The availability human, mouse and, most recently, rat genome sequences now permit evolutionary change. Results: Human are unevenly distributed among chromosomes highly represented (99.5%) human-rodent ortholog sets. Differences revealed in selection between different categories genes. Although appears not greatly discriminated non-disease genes, synonymous substitution higher for In neurological malformation syndrome systems, evolved slowly whereas immune, hematological pulmonary systems changed more rapidly. Amino-acid substitutions inherited occur at sites that conserved than average; nevertheless, 15 substituting amino acids were identified wild- type rat. Rodent trinucleotide repeat-expansion found contain fewer such repeats. Six share same characteristics triplet disease- identified; although four these expressed brain, none is currently known be Conclusions: Most been retained genomes. Synonymous nucleotide a rate finding may reflect increased mutation chromosomal regions which found. function exhibit greatest conservation; this suggests models likely faithfully represent processes. However, regard repeat expansion-associated contraction, relative repeats loci achieve 'critical threshold' necessary undergo spontaneous pathological expansions. identification six study multiple expansion-disease raises possibility all capable facilitating by expansion yet identified.