title: Origin and evolution of the c.844_845ins68/c.833T>C mutations within the cystathionine beta-synthase gene in great apes.
abstract: The c.[833C; 844_845ins68] is a common haplotype of the human cystathionine beta-synthase gene among healthy individuals. This polymorphism (5-40% allelic frequency in different populations) consists of the c.844_845ins68 insertion that segregates in cis with the pathogenic c.833T>C substitution (p.I278T). Through genotyping of primates, we have found that gorillas, chimpanzees and bonobos are homozygous for the 68bp insertion, c.844_845ins68. In gorillas and bonobos, the c.844_845ins68 lesion segregates in cis with the wild-type c.833T variant, whilst chimpanzees present the human haplotype. These genetic evidences suggest that the origin of the 68bp insertion might be dated back to 6-8 million years ago, and that the c.833T>C substitution occurred within the allele carrying the insertion. The evolutionary conservation of this peculiar haplotype supports the hypothesis of its protective effects against cardiovascular diseases.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Romano
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
mesh_terms: D000818:Animals; D001483:Base Sequence; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D019143:Evolution, Molecular; D006579:Heterozygote; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics*
chemical_list: D003541:Cystathionine beta-Synthase