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J S Beckmann

Publications and source records attributed to J S Beckmann.

At least 109 records · Page 6Linked to original sources
PubMed1993

Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11.

Familial hypertrophic cardiomyopathy (FHC) is a cardiac disorder transmitted as an autosomal dominant trait. FHC has been shown to be genetically heterogeneous with less than 50% of published pedigrees being associated with mutations in the beta myosin heavy chain (beta-MHC) gene on chromosome 14q11-q12. A second locus has recently been reported on chromosome 1. We examined the segregation of microsatellite markers in a French pedigree for which the disease is not linked to beta-MHC gene. We found significant linkage of the disease locus to several (CA)n repeats located on chromosome 11 (lod scores between +3.3 and +4.98). The data suggest the localization of the novel FHC gene in a region spanning 17 centiMorgans.

Cardiomyopathy, Hypertrophic↗
PubMed1993

A linkage map of human chromosome 15 with an average resolution of 2 cM and containing 55 polymorphic microsatellites.

We have constructed a 2.0 centiMorgan (cM) resolution genetic linkage map for chromosome 15q that contains 55 polymorphic satellites and 3 RFLPs that have placed on the map with odds for order of at least 1,000:1. Genotypes from 67 polymorphic loci (64 polymorphic microsatellites) were used to construct the map. Nine genes are included in the 1,000:1 map and 37 markers have heterozygosities of at least 70%. The sex-equal map length is 128 cM and the largest genetic interval is 11 cM (15.5 cM on the female map). The female and male map lengths are 150 cM and 106 cM, respectively. The map was constructed with 'MultiMap' and is based on the CEPH reference pedigrees and includes over 12,000 new genotypes. A sub-set of 12 markers spanning the length of the linkage map were genotyped in a somatic cell hybrid panel with breakpoints that divided 15q into five segments. Cytogenetic placement agreed with the linkage positions for each of the microsatellites tested with the exception of one (ACTC) which failed to give consistent results. Ten spontaneous new mutations were identified from a subset of 42 polymorphic microsatellites (out of a total of 20,420 transmissions), giving an apparent observed spontaneous mutation rate of 5 x 10(-4) per locus. An integrated map of chromosome 15q was also constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. The sex average map spans 144.7 cM with an average distance between unique map locations of 3.5 cM and a maximum intermarker distance of 11.5 cM. These genetic linkage maps can be considered baseline maps for 15q which will be useful for physical mapping and the localization of disease genes and other genes of interest.

Base Sequence↗
PubMed1993

Severe childhood autosomal recessive muscular dystrophy with the deficiency of the 50 kDa dystrophin-associated glycoprotein maps to chromosome 13q12.

We have recently demonstrated the specific deficiency for the 50 kDa dystrophin-associated glycoprotein (50DAG) in Algerian patients afflicted with severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD). A similar disease affecting Tunisian patients was linked to chromosome 13q but the status of the 50DAG was not investigated. Here we show by linkage analysis of Algerian families that the genetic defect which leads, either directly or indirectly, to the deficiency of the 50DAG in skeletal muscle is localized to the proximal part of chromosome 13q. We have not found any evidence of genetic heterogeneity among the thirteen families studied. It remains to be demonstrated whether the 50DAG gene maps at 13q12, and to determine if it is mutated in this disease.

Child↗
PubMed1993

Estimating locus heterogeneity in autosomal dominant polycystic kidney disease (ADPKD) in the Spanish population.

Although most mutations causing ADPKD in European populations have been mapped to the PKD1 locus on chromosome 16, some of them appear to be unlinked to this locus. To evaluate the incidence of unlinked mutations in Spain we have typed 31 Spanish families from different geographical sites for six closely linked DNA polymorphic marker loci flanking PKD1 detected by probes D16S85, D16S21, D16S259, D16S125, D16S246, and D16S80. Multilocus linkage analysis indicated that in 26 families the disease resulted from PKD1 mutations, whereas in three families it resulted from mutations in a locus other than PKD1. The two other families were not informative. Using the HOMOG test, the incidence of the PKD1 linked mutations in Spain is 85%. Multipoint linkage analysis in the 26 PKD1 families showed that the disease locus lies in the interval between D16S259(pGGG1) and D16S125(26.6).

Alleles↗
PubMed1993

Exclusion of genes coding for proteins of the cytoskeleton and the extracellular matrix in familial hypertrophic cardiomyopathy using a candidate gene approach.

Familial hypertrophic cardiomyopathy (FHC), a primary cardiac pathology, is a genetically heterogeneous disease, with autosomal dominant inheritance. The first gene identified as responsible for FHC codes for beta-myosin heavy chain (beta-MHC). To find a second locus, a candidate gene approach was applied on two families for which the beta-MHC locus was excluded. Selection of candidate genes is based on the observation of tissular and cellular disorganisation in FHC, and included genes coding for proteins involved in human myocardium architecture: the extracellular matrix components and cytoskeleton proteins. Chromosomal areas containing the candidate genes were examined by linkage analysis with microsatellite markers. The genes coding for different types of collagens, laminins, fibronectin, fibrillins, desmin, titin, alpha-actinin, vinculin, cardiac and skeletal alpha-actins, ankyrin and spectrin were excluded as responsible for FHC.

Cardiomyopathy, Hypertrophic↗
PubMed1992

Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci.

Hypokalemic periodic paralysis (HOKPP) is an autosomal dominant neuromuscular disorder characterized by flaccid paralysis accompanied by lowered serum potassium levels. We have tested polymorphic markers linked to the adult skeletal muscle sodium channel (SCN4A) locus at 17q23-q25, the T-cell receptor beta (TCRB) locus at 7q35, and the H-Ras cellular proton-cogene locus (HRAS) at 11p15.5 for linkage with the affected phenotype in a single multigenerational pedigree. No evidence for genetic linkage to HOKPP was found at any of the candidate loci.

Chromosome Mapping↗
PubMed1992

Mapping of the formin gene and exclusion as a candidate gene for the autosomal recessive form of limb-girdle muscular dystrophy.

Limb-Girdle Muscular Dystrophy (LGMD) is a myopathy with clinical and transmission heterogeneity. The recessive form, LGMD2, has been recently mapped by linkage analysis to 15q. As an attempt to identify the gene involved in this pathology, we tested as candidate gene the LD locus, called LD for limb deformity. This gene has recently been identified and mapped to chromosome 15q13-q14. It is homologous to the murine formin gene which is localized to mouse chromosome 2. Mutations in this murine gene have been shown to cause limb deformity and kidney defect. YAC clones containing the LD gene were isolated and utilised to confirm the cytogenetic localisation. Internal DNA polymorphisms of the LD locus were analyzed in LGMD2 and CEPH families. The LD gene was mapped between the alpha cardiac actin gene and the D15S24 locus. Crossovers between the LGMD2 and the LD loci excluded the LD gene as a candidate for LGMD2.

Base Sequence↗