Germline mutations in patients with hemophilia B generally have arisen within the past 150 years.
Evidence suggests that these germline mutations generally result from endogenous processes.
However, a unique pattern would be expected if a population were exposed to a physiologically important germline mutagen since mutagens generally produce characteristic patterns, or « fingerprints », of mutation.
To determine the pattern of mutation in Mexican Hispanics, the regions of likely functional significance in the factor IX gene were screened by dideoxy fingerprinting (ddF) in 31 families with hemophilia B. Mutations were found in 30 of these families.
Haplotype analysis was performed on individuals with identical mutations to help distinguish independent, recurrent mutations from founder effects.
Analysis of these 30 mutations, along with 7 mutations reported previously in Mexican Hispanic families, reveals a pattern of independent mutation that is similar to the pattern of mutation observed in 127 U. S. Caucasian families (p=0.89).
These results may reflect either an underlying pattern of germline mutation due to endogenous processes or the presence of an ubiquitous mutagen.
Further analyses of the recurrent mutations revealed that two mutations, T296M and R248Q, accounted for 19% of the mutations found in the Mexicans.
Haplotype data suggest that the multiple occurrences of T296M and R248Q are associated with founder effects and that screening for these mutati...
Mots-clés Pascal : Hémophilie B, Facteur antihémophilique B, Facteur coagulation, Lignée germinale, Mutation, Gène, Epidémiologie moléculaire, Latinoaméricain, Mexique, Amérique Centrale, Amérique, Homme, Hémopathie, Coagulopathie, Maladie héréditaire
Mots-clés Pascal anglais : Hemophilia B, Factor IX, Coagulation factor, Germ line, Mutation, Gene, Molecular epidemiology, Latinamerican, Mexico, Central America, America, Human, Hemopathy, Coagulopathy, Genetic disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0066043
Code Inist : 002B19C. Création : 199608.