RESUMO
The locus DXS134 (cpX67) has been physically linked to the cluster of polymorphic loci DXS52, DXS15, and DXS33. A comparison of physical and genetic distance indicates a high rate of recombination in this region.
Assuntos
Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Cromossomo X/ultraestrutura , Ligação Genética , Haplótipos , Humanos , Recombinação Genética , Mapeamento por RestriçãoRESUMO
It is now possible to map almost any disease locus to a chromosomal region in the human genome by family studies with restriction fragment length polymorphisms. Duchenne and Becker muscular dystrophies have been shown to be localized within the same small region of Xp21 on the human X chromosome. Myotonic dystrophy has been localized to a region close to the centromere of chromosome 19. Technologies are now available to identify candidate genes for the diseases. Autosomal recessive muscular dystrophies are more difficult to study, but even these will be amenable to analysis in the very near future. The next decade should witness some exciting advances in the molecular analysis and clinical management of human muscular dystrophies.
Assuntos
Distrofias Musculares/genética , Mapeamento Cromossômico , Cromossomos/análise , DNA/análise , Eletroforese/métodos , Código Genético , Ligação Genética , Marcadores Genéticos , Humanos , Distrofias Musculares/classificação , Distrofias Musculares/fisiopatologiaRESUMO
Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8 (DXS98), and St14 (DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Etude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies (theta) corresponding to maximum LOD scores (Z) were obtained by two-point linkage analysis for a number of linkage groups, including: DXS51-F9 (Z = 5.94, theta = 0.03), F9-DXS98 (Z = 0.51, theta = 0.26), F9-DXS52 (Z = 0.84, theta = 0.27), and DXS98-DXS52 (Z = 0.32, theta = 0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 (Z = 9.96, theta = 0) and F9-DXS52 (Z = 0.07, theta = 0.45) as well as for the groups DXS51-FRAXA (Z = 2.42, theta = 0.15), F9-FRAXA (Z = 1.30, theta = 0.18), DXS98-FRAXA (Z = 0.05, theta = 0.36), and DXS52-FRAXA (Z = 2.42, theta = 0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P less than 0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.
Assuntos
DNA/isolamento & purificação , Síndrome do Cromossomo X Frágil/genética , Ligação Genética , Polimorfismo Genético , Aberrações dos Cromossomos Sexuais/genética , Células Cultivadas , DNA/genética , Feminino , Humanos , Masculino , Linhagem , Recombinação Genética , Valores de ReferênciaRESUMO
Previous studies have reported that malignant hyperthermia susceptibility is caused in some families by inherited variation in a gene located on the short arm of chromosome 19 near to, or identical with, the ryanodine receptor gene (RYR1); this is expressed in skeletal muscle as a calcium release channel of the sarcoplasm reticulum. In other families, a gene in this location is excluded, but the locations of the genes involved have not yet been defined. We have analysed DNA samples from members of three large British families in whom in vitro muscle contracture tests for malignant hyperthermia susceptibility have been carried out in accordance with the procedure recommended by the European Malignant Hyperthermia Group. The results presented here strongly suggest that the gene for malignant hyperthermia susceptibility in one or more of these three British families is located in the same region of chromosome 19q, although further work is required to decide whether or not the RYR1 gene itself is causative in these families. As genetic heterogeneity could not be excluded, we cannot yet recommend the use of DNA markers to replace in vitro contracture tests in the diagnosis of malignant hyperthermia susceptibility.