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)

Usher Syndrome Type 1 is an autosomal recessive disease characterized by profound congenital hearing impairement and vestibular dysfunction followed by the onset of retinitis pigmentosa in childhood or early adolescence. Members of the Usher Syndrome Consortium, whose objective is to locate and isolate the genes for Usher syndrome, have pooled linkage data from 36 families with 111 affected individuals. We report the analysis of 206 blood group, protein, and DNA marker polymorphisms. No evidence of linkage heterogeneity among families was found for any of the markers studied; the negative lod scores exclude the locus for this disease from about 39% of the genome. Our results indicate the regions of the genome to which our continuing efforts should be directed.
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PMID:Linkage studies of Usher syndrome type 1: exclusion results from the Usher syndrome consortium. 142 98

Usher syndrome is a heterogeneous group of autosomal recessive disorders that combines variably severe congenital neurosensory hearing impairment with progressive night-blindness and visual loss similar to that in retinitis pigmentosa. Usher syndrome type I is distinguished by profound congenital (preverbal) deafness and retinal disease with onset in the first decade of life. Usher syndrome type II is characterized by partial hearing impairment and retinal dystrophy that occurs in late adolescence or early adulthood. The chromosomal assignment and the regional localization of the genetic mutation(s) causing the Usher syndromes are unknown. We analyzed a panel of polymorphic genomic markers for linkage to the disease gene among six families with Usher syndrome type I and 22 families with Usher syndrome type II. Significant linkage was established between Usher syndrome type II and the DNA marker locus THH33 (D1S81), which maps to chromosome 1q. The most likely location of the disease gene is at a map distance of 9 cM from THH33 (lod score 6.5). The same marker failed to show linkage in families segregating an allele for Usher syndrome type I. These data confirm the provisional assignment of the locus for Usher syndrome type II to the distal end of chromosome 1q and demonstrate that the clinical heterogeneity between Usher types I and II is caused by mutational events at different genetic loci. Regional localization has the potential to improve carrier detection and to provide antenatal diagnosis in families at risk for the disease.
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PMID:Mapping recessive ophthalmic diseases: linkage of the locus for Usher syndrome type II to a DNA marker on chromosome 1q. 197 8

Linkage of the anonymous DNA marker D3S47 (CRI-C17) and autosomal dominant retinitis pigmentosa (ADRP) was tested in a large, extended family with type II (late onset) ADRP. D3S47 has been shown previously to be tightly linked to the RP locus in one family with type I (early onset) ADRP (McWilliams et al., 1989, Genomics 5: 619-622). Linkage between ADRP type II and D3S47 has recently been excluded in a single family (Ingelhearn et al., 1990, Genomics 6: 168-173). Results of our linkage analysis clearly establish that type II ADRP in our family is unlinked to D3S47. These findings support the hypothesis that type II ADRP is genetically distinct from type I ADRP.
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PMID:Further evidence of exclusion of linkage between type II autosomal dominant retinitis pigmentosa (ADRP) and D3S47 on 3q. 208 94

Retinitis pigmentosa (RP) is an hereditary degenerative disease of the retina and a major cause of visual impairment, prevalence estimates ranging from 1 in 3000 to 1 in 7000. The condition may segregate as an autosomal dominant, autosomal recessive or an X-linked recessive trait and it may also occur on a sporadic basis in up to 50% of cases. In the autosomal dominant form, close linkage to the DNA marker C17 (D3S47) was recently established in a large family of Irish origin displaying early-onset disease (McWilliam et al. 1989), multipoint analysis indicating the gene for rhodopsin as a likely candidate (Farrar et al. 1990). In that gene, a C----A transversion in codon 23, resulting in a proline----histidine substitution has now been identified in 17 of 148 unrelated ADRP patients in the United States (Dryja et al. 1990). This mutation is absent however in the original Irish pedigree (it is also absent in 21 other dominant Irish pedigrees, representing approximately 70% of the estimated ADRP population) indicating that another mutation, either in rhodopsin itself, or in a gene very closely linked to rhodopsin is responsible for the disease in that family. Analysis of other dominant pedigrees using the C17 and/or rhodopsin probes has indicated either tight linkage (Bhattacharya, Personal Communication), looser linkage, possibly indicative of a second locus on 3q (Olsson et al. 1990) or no linkage (Farrar et al. 1990, Blanton et al. 1990, Inglehearn et al. 1990). Extensive genetic heterogeneity thus exists in the autosomal dominant form of this disease, and in the light of these new observations, earlier tentative evidence for linkage of ADRP to the Rhesus locus on chromosome 1 will be re-evaluated. A locus for type II Usher syndrome (classical RP combined with congenital pedial deafness, and normal vestibular function) has now been established on the long arm of chromosome 1 (Kimberling et al. 1990). Type I Usher families, in which hearing loss is more profound and vestibular function absent, do not segregate with the same chromosome 1q markers, indicating the existence of another, as yet unlocated gene. In the X-linked form of the disease, two genes, XLRP2 and XLRP3, have been located on the proximal short arm of the X chromosome using a combination of physical and linkage mapping techniques, and there is some evidence to suggest a possible third locus more distally located.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retinitis pigmentosa: genetic mapping in X-linked and autosomal forms of the disease. 220 66

Retinitis pigmentosa (RP) is the most common hereditary dystrophic disease of the retina. About 10% of the affected families show the X-linked trait. The close link observed between the gene locus (RP2) and a polymorphic DNA marker (DXS7) on the proximal short arm of the X-chromosome permits an indirect genotype diagnosis and can be helpful in carrier detection and genetic counseling. A case is presented in which the carrier risk of a female consultant dropped from 50% a priori to less than 2% by the use of clinical findings and DNA analysis.
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PMID:[Molecular genetic diagnosis in X chromosome-linked retinitis pigmentosa]. 289 68

A hypervariable DNA marker is closely linked to one of the most severe forms of night blindness, X-linked retinitis pigmentosa (RP). Affected individuals with X-linked RP, obligate carriers, and ophthalmologically identifiable carriers of the disease were included in a linkage study. The diagnosis was established in five sibships by funduscopic and electrophysiological investigations. When the X-linked probe M27 beta was used, 2 recombinants out of 29 informative meioses were detected (theta = 0.07 at a maximum lod of 4.75). The hypervariable probe detected two different alleles in 38 of 39 females tested. M27 beta is therefore a potentially very useful probe for carrier detection and prenatal diagnosis, as well as for addressing the question of heterogeneity of X-linked RP.
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PMID:Linkage of X-linked retinitis pigmentosa to the hypervariable DNA marker M27 beta (DXS255). 292 Oct 39

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

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yielded a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families.
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PMID:Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa. 857 61