To localize disease genes for scleroderma, or systemic sclerosis (SSc), in a population of Choctaw Native Americans with a high prevalence of SSc, in which there is evidence of a possible founder effect.
A candidate gene approach was used in which microsatellite alleles on human chromosomes 15q and 2q, homologous to the murine tight skin 1 (tsk1) and tsk2 loci, respectively, were analyzed in Choctaw SSc cases and race-matched normal controls for possible disease association.
Genotyping first-degree relatives of the cases identified potential disease haplotypes, and haplotype frequencies were obtained by expectation-maximization and maximum-likelihood estimation methods.
Simultaneously, the ancestral origins of contemporary Choctaw SSc cases were ascertained using census and historical records.
A multilocus 2-cM haplotype was identified on human chromosome 15q homologous to the murine tsk1 region, which showed a significantly increased frequency in SSc cases compared with controls.
This haplotype contains 2 intragenic markers for the fibrillin I (FBN1) gene.
Genealogical studies demonstrated that the SSc cases were distantly related, and their ancestry could be traced back to 5 founding families in the mid-eighteenth century.
The probability that the SSc cases share this haplotype due to familial aggregation effects alone was calculated and found to be very low. (...)
Mots-clés Pascal : Sclérodermie, Pathogénie, Homme, Epidémiologie, Prévalence, Oklahoma, Etats Unis, Amérique du Nord, Amérique, Américain, Déterminisme génétique, DNA microsatellite, Réaction chaîne polymérase, Génétique, Exploration, Peau pathologie, Tissu conjonctif pathologie, Maladie système, Maladie autoimmune, Immunopathologie, Biologie moléculaire, Gène FBN1
Mots-clés Pascal anglais : Scleroderma, Pathogenesis, Human, Epidemiology, Prevalence, Oklahoma, United States, North America, America, American, Genetic determinism, Microsatellite DNA, Polymerase chain reaction, Genetics, Exploration, Skin disease, Connective tissue disease, Systemic disease, Autoimmune disease, Immunopathology, Molecular biology
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0500083
Code Inist : 002B07. Création : 19/02/1999.