Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012872 (DNA marker)
 929 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied twin sisters, in their sixth decade, who were obligate carriers of Duchenne dystrophy. One had a slowly progressing limb-girdle myopathy since her mid-20s. The other sister showed no evidence of neuromuscular disease by history or on physical examination but had high serum CK values and degeneration and regeneration of fibers in a muscle biopsy. Otherwise, they were phenotypically identical, karyotypically normal females with cytogenetically normal X-chromosomes. Based on red cell and HLA loci antigen determinations, there was a 99.2% probability that they were monozygotic. The mutant gene segregating in the family is probably linked to the Xp21 DNA marker pERT87.
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PMID:Monozygotic female twin carriers discordant for the clinical manifestations of Duchenne muscular dystrophy. 288 83

DNA sequence polymorphisms (RFLPs) have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne muscular dystrophy (DMD) in affected families, but serious limitations and pitfalls are associated with this approach [Darras et al., 1987]. The complementary DNA (cDNA) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients [Koenig et al., 1987]. Two prenatal studies are presented to illustrate how the unambiguous identification of deletion mutations by cDNA probes permits direct DNA-based diagnoses with high accuracy and in otherwise uninformative families. In a single proband family, DNA marker analysis had determined that the Xp21 chromosomal region present in the affected male was also carried by a male fetus in a subsequent pregnancy. Analysis of this family's DNA with probes covering the entire 14 kb cDNA revealed a small deletion in the affected male that was not present in the fetus nor in the mother. In the second family the fetus was a female deletion carrier identified by comparing intensities of restriction fragments. Since 1/3 of all DMD patients are thought to result from new mutations and most families have only single affected males, the cloned cDNA probes now available are likely to revolutionize DNA-based diagnostic studies in this disorder. More reliable, more rapid and less expensive than linkage studies with DNA polymorphisms, this method will be informative in the more than 50% of DMD/BMD cases that have deletion mutations.
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PMID:Direct method for prenatal diagnosis and carrier detection in Duchenne/Becker muscular dystrophy using the entire dystrophin cDNA. 289 93

Friedreich's ataxia is an autosomal recessive disease with progressive degeneration of the central and peripheral nervous system. The biochemical abnormality underlying the disorder has not been identified. Prompted by the success in localizing the mutations causing Duchenne muscular dystrophy, Huntington's disease and cystic fibrosis, we have undertaken molecular genetic linkage studies to determine the chromosomal site of the Friedreich's ataxia mutation as an initial step towards the isolation and characterization of the defective gene. We report the assignment of the gene mutation for this disorder to chromosome 9p22-CEN by genetic linkage to an anonymous DNA marker MCT112 and the interferon-beta gene probe. In contrast to the clinical variation seen for the disorder, no evidence of genetic heterogeneity is observed.
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PMID:Mapping of mutation causing Friedreich's ataxia to human chromosome 9. 289 44

A DNA marker C7, localised Xp21.1-Xp21.3, has been studied in kindreds segregating for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In DMD families four crossovers were observed in 38 informative meioses between C7 and the DMD locus (theta = 0.12, z max = +2.72). In BMD families no recombinants were observed in the 16 informative meioses studied. These data are consistent with the localisation of the mutations in these disorders being in the same region of Xp21. Studies in families also segregating for the DNA marker 754 support the previously reported physical order of these loci as X centromere-754-DMD-BMD-C7-X telomere. A recombination fraction of 0.11 (z max = +5.58) was found between DMD-754 by combining our previously published data with the data presented here. C7 and 754 thus provide good bridging markers for the diagnosis of DMD and BMD.
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PMID:Segregation analysis of a marker localised Xp21.2-Xp21.3 in Duchenne and Becker muscular dystrophy families. 299 31

We revisited a family with the Coffin-Lowry syndrome (CLS) first reported by Procopis and Turner in 1972. Twelve affected members are now known in 3 generations of which 9 were seen personally. DNA marker studies supported X-linkage with localization of CLS to Xp near DXS43 at p22.2-22.1 (theta = 0.001 Z = 2.71). Such linkage is reinforced by positive lod scores for DXS28 (theta = 0.00, Z = 0.90) and for DXS84 (theta = 0.09, Z = 1.56). Recombination with DXS84 and DXS164 places CLS distal to DMD in Xp21-pter.
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PMID:A family with the Coffin Lowry syndrome revisited: localization of CLS to Xp21-pter. 317 68

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.
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PMID:DNA linkage studies of degenerative retinal diseases. 331 43

The program DUCHEN calculates the probability that a woman is a carrier of an X-linked, lethal recessive disease on the basis of information in the woman's family and any available biochemical data. It is easily used by persons without computer knowledge or experience. The present version can accommodate families consisting of up to 100 people in seven generations. Risks may be estimated on the basis of pedigree information only, or with the inclusion of one or more types of biochemical test results. Biochemical data are incorporated with pedigree information into final risks using the powerful statistical technique of logistic discrimination, a procedure particularly suited for the separation of non-normal populations on the basis of overlapping quantitative characteristics. Mutation rates are specified separately for males and females. DUCHEN is available in FORTRAN 77, IBM BASIC, and Applesoft BASIC, and may be used on a variety of mainframe or microcomputers. The model was used to calculate risks for 375 girls and women in 46 families with Duchenne muscular dystrophy (DMD); serum creatine kinase tests had been carried out on 167 of these subjects who were of reproductive age. Carrier probabilities equal to or lower than the population risk (0.0004) were obtained for 21% of the aunts and 43% of the cousins of affected boys from families with an isolated case of DMD and for 14% of the cousins of affected boys from families with a known DMD history. DUCHEN should assist counsellors in determining which members of large families should be further examined using either standard biochemical carrier detection methods or DNA marker studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:DUCHEN: an interactive computer program for calculating heterozygosity (carrier) risks in X-linked recessive lethal diseases, and its application in Duchenne muscular dystrophy. 377 18

A database useful for mapping the human X chromosome has been established. The data consist of the genotypic characterizations obtained at more than 20 DNA marker loci from a set of 38 selected families. Multilocus linkage analysis has provided an initial genetic map completely spanning the distance from the distal short arm to the distal long arm of the chromosome, for a total genetic length of at least 185 recombination units. Analysis of the recombinational behavior of fully marked chromosomes suggests that the number of recombination events on the X chromosome may be nonrandom. Linkage studies of six families that carry the mutation which causes Duchenne muscular dystrophy were combined with linkage data from a large number of normal families. This permitted mapping of the locus for Duchenne muscular dystrophy with greater precision and statistical confidence than studies in which disease families alone provided the genotypic database. This observation suggests that the normal linkage map of this chromosome should be especially valuable in the mapping of rare X-linked diseases.
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PMID:The genetic linkage map of the human X chromosome. 405 9

Seventy families with Duchenne muscular dystrophy (DMD) known to the Institute of Child Health fall into three categories with respect to potential linkage analysis with the X chromosome DNA markers RC8 and L1.28 that bridge the DMD gene. Families in which there is at least one obligatory female heterozygote (n = 13). Here 'prediction' and 'exclusion' of DMD gene transmission may be possible, the accuracy being dependent on the closeness of the linkage of the DNA marker(s) to the DMD gene; an illustrative case is reported. Families in which there is a single affected boy, who also has one or more healthy brothers (n = 26). Given an informative restriction fragment length polymorphism (RFLP), the probability that the boy represents a new mutation can be reassessed; it is also possible to 'exclude' the DMD gene in a sister. Families with a single affected boy with no brother (n = 30). Here 'exclusion' of the DMD gene in a sister may be possible. Only in one family was there no possibility of useful linkage analysis. The linkage analysis required is described, and the need to check DMD families for informative RFLPs is stressed.
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PMID:Clinical use of DNA markers linked to the gene for Duchenne muscular dystrophy. 658 84

This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system's successful diagnosis of DMD carrier and affected individuals from raw clinical data.
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PMID:Intelligent DNA-based molecular diagnostics using linked genetic markers. 758 9


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