title: Linkage disequilibrium between IDUA kpnI-VNTR haplotype in Mexican patients with MPS-I.
abstract: BACKGROUND
  The MPS-I is an autosomal recessive disorder caused by mutations in the IDUA gene that induce to a deficiency of glycosidase alpha-L-iduronidase that is required for degradation of heparan and dermatan sulfate. This disorder expresses a wide range of clinical symptoms.
  
  
  METHODS
  Kpnl (K) and VNTR (V) intragenic polymorphisms at the IDUA gene were studied in mestizo and Huichol Indian Mexican populations as well in 13 MPS-I patients. Data from Australian normal and MPS-I (2-4) individuals were also studied.
  
  
  RESULTS
  Genotypes for IDUA K and V sites in Mexicans were in agreement with Hardy-Weinberg expectations, except for site K in Huichols. Individually, allele frequency distributions were different (p < 0.05) in the two normal groups for the V site. K-V haplotype frequency distributions (HFDs) in these two normal groups were also different as compared with normal Australians. In Mexican MPS-I patients, HFD was different (p < 0.05) with respect to both Mexican normal groups, and non-different when compared with normal or MPS-I Australians. This can be taken as evidence of linkage disequilibrium between K-V polymorphism and MPS-I gene mutation(s) at the IDUA region. A similar finding was reported. However, disequilibrium in Mexicans was determined by haplotypes different from those in Australia. In Mexican MPS-I patients, haplotype K2-V1 is increased and K1-V3 decreased with respect to the Mexican mestizo (p < 0.05), while in Australians, MPS-I patients had an increase of haplotypes K2-V2 and K1-V2 with respect to expected frequency.
  
  
  CONCLUSIONS
  The similar HFD between Mexican and Australian MPS-I patients suggests a common genetic origin, that MPS-I mutations were introduced to Mexico by Spaniards, and that such mutations predate the dispersion between Mexican and Australian Caucasian ancestors. The differences in disequilibrium are explained rather by genetic drift.
authors.affiliation: División de Medicina Molecular, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico. marthaga@foreigner.class.udg.mx
authors.forename: M
authors.initials: M
authors.lastname: Gallegos-Arreola
authors.forename: F
authors.initials: F
authors.lastname: Rivas-Solis
authors.forename: S
authors.initials: S
authors.lastname: Flores-Martínez
authors.forename: G
authors.initials: G
authors.lastname: Zúñiga-González
authors.forename: L
authors.initials: L
authors.lastname: Sandoval-Ramírez
authors.forename: J M
authors.initials: JM
authors.lastname: Cantú-Garza
authors.forename: C
authors.initials: C
authors.lastname: Ranaji
authors.forename: L
authors.initials: L
authors.lastname: Figuera
authors.forename: M C
authors.initials: MC
authors.lastname: Morán-Moguel
authors.forename: J
authors.initials: J
authors.lastname: Sánchez Corona
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008800:Mexico; D018598:Minisatellite Repeats; D008059:Mucopolysaccharidosis I / Q000208:ethnology / Q000235:genetics*
chemical_list: D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; C029312:GGTACC-specific type II deoxyribonucleases