title: Epistatic interactions: how strong in disease and evolution?
abstract: When the chimpanzee genome sequence was released, human deleterious alleles associated with simple mendelian diseases were observed as wild-type alleles in six genes (AIRE, MKKS, MLH1, MYOC, OTC and PRSS1). The absence of recognizable phenotypic effects in chimpanzee, contrary to the clinical effect observed in humans, is attributed to epistatic interactions (compensation) between potentially deleterious and compensatory alleles. In this report we investigate the possible evolutionary histories by which substitution of alternative variants in these six genes either ameliorates or avoids pathological consequences.
authors.affiliation: IPATIMUP, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal. luisa.azevedo@ipatimup.pt
authors.forename: Luísa
authors.initials: L
authors.lastname: Azevedo
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
authors.forename: Barbara
authors.initials: B
authors.lastname: van Asch
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: Harding
authors.forename: António
authors.initials: A
authors.lastname: Amorim
mesh_terms: D000220:Adaptation, Biological; D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D002352:Carrier Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004303:Dosage Compensation, Genetic; D004843:Epistasis, Genetic; D005136:Eye Proteins / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D056385:Group II Chaperonins; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D002679:Pan troglodytes / Q000235:genetics; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics; D000096927:AIRE Protein; D000099179:Myocilin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D056385:Group II Chaperonins; D018832:Molecular Chaperones; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins; D014157:Transcription Factors; D014357:Trypsin; D014362:Trypsinogen; D000096927:AIRE Protein; D000099179:Myocilin; C414726:MKKS protein, human; C501486:MLH1 protein, human; C489303:PRSS1 protein, human