title: XV-2c/KM-19 haplotype analysis of cystic fibrosis mutations in Mexican patients.
abstract: We analyzed 97 unrelated Mexican cystic fibrosis (CF) patients and their first-degree relatives to study the association of XV2C/TaqI/KM19/PstI haplotypes with CF mutations in this population. Haplotype phases could be established in 148 CF and 110 normal chromosomes, and haplotype distributions of normal and CF chromosomes differed significantly (P < 0.001). DeltaF508 and G542X mutations accounted for 56% of CF chromosomes and were found to be associated with haplotype B in 97.2% and 72.7% of chromosomes, respectively. The haplotype distribution of CF chromosomes carrying other rare and unknown mutations was similar to that of normal chromosomes (P > 0.05), haplotypes A and C being the most frequent. This is in accordance with the extensive heterogeneity and the spectrum of mutations reported in Mexican CF patients. We also report the haplotype distribution of all informative chromosomes bearing rare mutations; some were found to be associated with previously reported haplotypes, whereas others were found on different haplotypes. Recombination or recurrence of mutations may explain these different associations, although other intragenic markers must be used to better understand the origin and dispersion of CF mutations in our country. XK haplotype analysis allowed carrier detection among sibs in 24.3% of families, showing that this method may be useful for carrier detection in populations with high allelic heterogeneity.
authors.affiliation: Molecular Biology Laboratory, Department of Research in Human Genetics, National Institute of Pediatrics, Mexico City, Mexico. lorozco@buzon.main.conzcyt.mx
authors.forename: L
authors.initials: L
authors.lastname: Orozco
authors.forename: L
authors.initials: L
authors.lastname: González
authors.forename: M
authors.initials: M
authors.lastname: Chávez
authors.forename: R
authors.initials: R
authors.lastname: Velázquez
authors.forename: J L
authors.initials: JL
authors.lastname: Lezana
authors.forename: Y
authors.initials: Y
authors.lastname: Saldaña
authors.forename: T
authors.initials: T
authors.lastname: Villarreal
authors.forename: A
authors.initials: A
authors.lastname: Carnevale
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008800:Mexico; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases