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J S Beckmann

Publications and source records attributed to J S Beckmann.

At least 19 recordsLinked to original sources
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Prenatal diagnosis of limb-girdle muscular dystrophy type 2A.

A branch of a highly inbred family was referred for prenatal counseling with an initial misdiagnosis of Becker Muscular Dystrophy (BMD) due to the limited clinical and laboratory data obtained in pre-dystrophin era and hidden family information. In a second branch of the family with a diagnosis of limb-girdle muscular dystrophy type 2A (LGMD2A) molecular studies revealed a homozygous 550 delta A mutation in the calcium-activated neutral protease 3 (calpain 3, CANP3) gene in the affected members. Finally, in the third branch of the family, it turned out that both parents were heterozygous for the 550 delta A mutation and the 13-week-old fetus was homozygous. The same mutation subsequently also was found in the first branch of the family. The parents were informed that the risk of their child of developing the disease would be very high given that he was carrying the same homozygous mutation of the other affected members. They were informed also that in another population (in Reunion Island) the same disease does not necessarily follow such a simple pattern of inheritance. After counseling the parents decided to terminate the pregnancy.

Adult↗
PubMed1996

Chromosome 15-linked limb-girdle muscular dystrophy: clinical phenotypes in Reunion Island and French metropolitan communities.

Erb's type limb-girdle muscular dystrophy (LGMD) was identified and clinically studied in detail in a small community living in the Reunion Island (RI). It was linked to chromosome 15q and related to mutations in the muscle specific calpain 3 gene. A series of cases were afterwards clinically and genetically identified in the French metropolitan community. The phenotype was identical to the RI type in the great majority of cases, although clinical differences were noticed in a few cases. Six different mutations were identified in the RI families, whereas a series of 39 mutations were detected in the French metropolitan families, all different from those present in the RI patients. Phenotype-genotype correlations were attempted in both communities.

Adolescent↗
PubMed1996

A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India.

We investigated the molecular basis of a severe form of early onset autosomal recessive muscular dystrophy with sarcoglycan (SG) deficiency in seven large Gypsy families living in different parts of Western Europe and apparently not closely related. They were linked to the LGMD2C locus (13q12) suggesting a primary defect in the gamma-SG gene coding for the 35 kDa dystrophin-associated glycoprotein. All of the 18 investigated patients were homozygous for the same G-->A transition in codon 283 producing the replacement of a conserved cysteine of the extra-cellular domain of the protein by a tyrosine. All affected chromosomes in homozygous and heterozygous relatives carried the same allele 5 of the intragenic marker D13S232. Flanking markers were studied to delineate a common ancestral haplotype, the size of which was used to compute the date of the founding mutation. We found evidence that the mutation occurred between 60 and 200 generations ago, therefore possibly predating the commonly accepted date of migration of the Gypsy ancestors out of India.

Biomarkers↗
PubMed1996

Advances in the molecular genetics of the limb-girdle type of autosomal recessive progressive muscular dystrophy.

A reclassification of the limb-girdle types of autosomal recessive muscular dystrophy based on genetic and protein information has been made possible by major advances over the past 2 years. At least six different forms of limb-girdle types of autosomal recessive muscular dystrophy can be defined by their genetic basis, with at least two pathogenic mechanisms involved. Three forms are defined by involvement of different proteins of the sarcoglycan complex, while a muscle specific protease (calpain 3) is implicated in another form of the recessive disease. These findings provide the basis for a new diagnostic approach to the group, with molecular techniques now an essential part of the diagnostic process. A scheme for diagnosis in this group is proposed.

Cytoskeletal Proteins↗
PubMed1996

Highly conserved structure in the promoter region of the gene for muscle-specific calpain, p94.

p94 belongs to the calcium-dependent cysteine protease (calpain) family which has been detected from human to mold. In contrast to the conventional m- and mu-calpains which are expressed ubiquitously, expression of p94 predominates in skeletal muscle, and the mRNA for p94 is at least 10-times more abundant than mRNAs encoding in the m- and mu-types. The unique feature of p94 is that it undergoes rapid and exhaustive autolysis with a half-life of less than half an hour. To elucidate the nature of specific and abundant expression in skeletal muscle, and to proceed toward gene targeting p94, we have cloned and characterized mouse and rat genes for p94, and compared them with that of the human sequence. The sequence comparison among three mammalian species revealed several conserved regions including possible transcription factor binding sites. Furthermore, mouse and rat upstream regions of p94 are conserved over 3 kb suggesting that expression of p94 in skeletal muscle of both rodents is similarly regulated.

Animals↗
PubMed1995

A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q.

Maturity-onset diabetes of the young (MODY) is a subtype of non-insulin dependent diabetes mellitus, with early age of onset. MODY is genetically heterogeneous, associated with glucokinase mutations and a locus on chromosome 20q; in about 50% of cases, its genetic background is unknown. We have studied 12 families in which MODY is unlinked to either glucokinase or chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on chromosome 12q, most likely within a 7 centimogran interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this chromosome region in approximately 50% of families in a heterogeneity analysis. These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic beta-cell function.

Adolescent↗
PubMed1995

Mapping a gene (SRN1) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis.

Idiopathic nephrotic syndrome (INS) in childhood is characterized by massive proteinuria and minimal glomerular changes. Most patients with INS respond to steroid therapy. INS is generally regarded as a sporadic disease with favorable outcome. We investigated a distinct subgroup of nephrosis--the familial form of steroid resistant INS (SRN). These patients always progress to end-stage renal failure within a few years and show absence of recurrence of the disease after renal transplantation. The occurrence of the disorder in siblings and the high incidence of inbreeding in these families made an autosomal recessive mode of inheritance very likely. We performed whole genome linkage analysis in nine multiplex families of European or Northern African origin. Our results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis. Exclusion of linkage to the entire region in one family proves genetic heterogeneity.

Chromosome Mapping↗
PubMed1995

Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus.

Limb-girdle muscular dystrophy (LGMD) is a hereditary myopathy presenting clinical and genetic heterogeneity. In 1991, a recessive form (LGMD2A) was linked to chromosome 15q in a genetic isolate from the Isle of La Réunion. Confirmation of this localization was subsequently reported in Brazilian and northern Indiana Amish pedigrees. Here we report the exclusion of the LGMD2A locus in six Amish kindreds from southern Indiana that are related by multiple consanguineous links to the same northern Indiana families in which the involvement of the chromosome 15 locus was previously demonstrated. These findings indicate unexpected genetic heterogeneity of LGMD in an Indiana Amish isolate. Furthermore, genetic analyses also ruled out the possible involvement of the chromosome 2 locus recently described (LGMD2B), thus demonstrating that a mutation within at least one additional locus leads to this condition. Several candidate genes putatively involved in neuromuscular disorders were also excluded.

Chromosomes, Human, Pair 15↗
PubMed1995

A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene.

Previous genetic and physical studies of LGMD2A, an autosomal recessive form of limb-girdle muscular dystrophy, have led to the establishment of a 10-12 Mb YAC contig encompassing the morbid locus. In order to progress toward the identification of the gene involved in LGMD2A, a primary transcription map of this genomic region was generated. The direct cDNA selection strategy was used with three YACs covering the candidate region and two different muscle cDNA libraries. Seventeen transcription units were identified among 171 cDNA fragments analysed. Five sequences corresponded to known genes, and twelve to new ones. They were characterized for their sequences, physical positions within the YAC contig, and expression patterns. Among those specifically transcribed in muscle, the calpain gene is a good positional and functional candidate for LGMD2A.

Adult↗
PubMed1994

Targeted development of microsatellite markers from inter-Alu amplification of YAC clones.

Primary genetic maps based on highly informative markers are now available. The local density of these markers may, however, not be sufficient. There is thus a need for new means to generate polymorphic markers from targeted regions of the genome. This can be achieved by selectively cloning and sequencing (CA)n-positive human inter-Alu sequences from targeted YAC clones. This method was tested on 21 YACs and led to the development of seven new polymorphic microsatellite markers.

Base Sequence↗