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R Oehlmann

Publications and source records attributed to R Oehlmann.

11 recordsLinked to original sources
PubMed1998

Evaluating a case-based discovery system: a case-study in content-oriented evaluation.

Research in case-based reasoning has explored the ideas of retrieving and adapting previous experience in the form of cases. The retrieval process uses an index vocabulary which attempts to capture content and context of previous cases. Current approaches to empirical evaluation of case-based reasoning systems often do not consider the crucial role which a content-oriented index vocabulary plays in the various stages of the case-based reasoning process. We will address this issue by describing an evaluation of our case-based discovery system IULIAN. Based on this description, we will propose a general schema for content-oriented evaluation of case-based reasoning systems.

Artificial Intelligence↗
PubMed1998

A susceptibility locus for Parkinson's disease maps to chromosome 2p13.

Parkinson's disease (PD) is a common degenerative neurologic disorder, which is pathologically characterized by a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta, and the presence of characteristic eosinophilic inclusions, known as Lewy-bodies in affected brain areas. The cause of PD is unknown but, in recent years, genetic factors have been implicated in the aetiology of the disease. Firstly, clinico-genetic, epidemiologic and twin studies revealed inheritable effects and questioned earlier studies which had denied such influences. Secondly, several family studies suggested autosomal-dominant inheritance of syndromes which, to variable degrees, resembled sporadic PD clinically and in some cases also neuropathologically. Recently, a disease locus has been mapped to chromosome 4q21-22 in a large Mediterranean pedigree, in which disease expression is clinically and pathologically within the spectrum of sporadic PD; being atypical only for a relatively young mean age at onset of 46 years and rapid course of 10 years from onset to death. In affected individuals of this family and of three unrelated Greek kindreds, a putative disease-causing mutation has been identified in the gene encoding alpha-synuclein. With the first variant being defined, genetic heterogeneity has become apparent, as in other families parkinsonism was not linked to the 4q-locus and was not associated with the alpha-synuclein mutation (unpublished data). We describe a different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). This locus was detected in a group of families of European origin. In two of these families, there is genetic evidence for a common founder. The penetrance of the mutation appears to be low, most likely below 40%. This is compatible with a possible role of this locus not only in familial, but also in typical (sporadic) PD.

Adult↗
PubMed1996

Autosomal recessive non-syndromic deafness locus (DFNB8) maps on chromosome 21q22 in a large consanguineous kindred from Pakistan.

Autosomal recessive childhood-onset non-syndromic deafness is one of the most frequent forms of inherited hearing impairment. Recently five different chromosomal regions, 7q31, 11q13.5, 13q12, 14q and the pericentromeric region of chromosome 17, have been shown to harbour disease loci for this type of neurosensory deafness. We have studied a large family from Pakistan, containing several consanguineous marriages and segregating for a recessive non-syndromic childhood-onset deafness. Linkage analysis mapped the disease locus (DFNB8) on the distal long arm of chromosome 21, most likely between D21S212 and D21S1225 with the highest lod score of 7.31 at theta = 0.00 for D21S1575 on 21q22.3.

Adolescent↗
PubMed1995

Autosomal recessive retinitis pigmentosa locus maps on chromosome 1q in a large consanguineous family from Pakistan.

A large Pakistani family with several consanguineous marriages is described, in which autosomal recessive retinitis pigmentosa is segregating. Linkage studies revealed close linkage between the disease locus and six loci on chromosome 1q (D1S158, F13B, D1S422, D1S412, D1S413, and D1S53) with maximum lod scores ranging from 0.988-4.657 at theta = 0.065-0.235. However, the analysis of individual nuclear families showed very close linkage without recombination in three branches and several recombinants and negative lod scores throughout in the fourth branch. These results strongly suggest that mutations of two different genes are responsible for the disease in the 'linked' and 'unlinked' branches. Parallel to the linkage heterogeneity, clear phenotypic differences have been observed among the 'linked' and 'unlinked' parts. Our findings demonstrate that in case of recessive disorders the possibility of non-allelic genetic heterogeneity should always be considered, even within the same kindred and in genetic isolates if a largely extended pedigree is analysed.

Chromosome Mapping↗
PubMed1995

Oguchi disease: suggestion of linkage to markers on chromosome 2q.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness. The condition is associated with fundus discolouration and abnormally slow dark adaptation. Earlier studies suggested that the 48 kD protein S antigen may be involved in the recovery phase of light transduction. Previous cytogenetic and linkage studies have localised the S antigen gene (SAG) to chromosome 2q37.1. In the present study markers which map to distal chromosome 2q were typed in an inbred Oguchi pedigree. The segregation data obtained suggested that the affected subjects are homozygous by descent for a region between D2S172 and D2S345. An intragenic SAG polymorphism was homozygous in all affected people and a recombination event suggested that SAG maps proximal to D2S345. Collectively, these findings support the hypothesis that a defect in S antigen may be responsible for Oguchi disease.

Antigens↗
PubMed1994

Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric region of chromosome 19.

Multiple epiphyseal dysplasia (MED) is an inherited chondrodystrophy that results in deformity of articular surfaces and in subsequent degenerative joint disease. The disease is inherited as an autosomal dominant trait with high penetrance. An MED mutation has been mapped by genetic linkage analysis of DNA polymorphisms in a single large pedigree. Close linkage of MED to 130 tested chromosomal markers was ruled out by discordant inheritance patterns. However, strong evidence for linkage of MED to markers in the pericentromeric region of chromosome 19 was obtained. The most closely linked marker was D19S215, with a maximum LOD score of 6.37 at theta = .05. Multipoint linkage analysis indicated that MED is located between D19S212 and D19S215, a map interval of 1.7 cM. Discovery of the map location of MED in this family will facilitate identification of the mutant gene. The closely linked DNA polymorphisms will also provide the means to determine whether other inherited chondrodystrophies have underlying defects in the same gene.

Centromere↗
PubMed1993

Exclusion of type II and type VI procollagen gene mutations in a five-generation family with multiple epiphyseal dysplasia.

We have studied a family with an autosomal dominant form of multiple epiphyseal dysplasia (MED) inherited through at least 5 generations. Bilateral deformity of the hips with subsequent degenerative arthritis was the most common and most severe change observed in the affected relatives. Abnormalities of the knees, ankles, and shoulders were also noted in some affected individuals. Radiological examination showed changes in affected joints consistent with epiphyseal dysplasia. In early stages, the articular surfaces appeared flattened or irregular in shape. In advanced stages, epiphyseal fragmentation, joint surface erosion, and extensive remodeling were observed. The abnormalities of the epiphyses suggested that the primary defect might be in a structural component of the epiphyseal cartilage matrix. The gene encoding type II collagen (COL2A1) was tested for genetic linkage to MED in this family by restriction fragment length polymorphism (RFLP) analysis. Recombination between COL2A1 and MED was observed, ruling out COL2A1 as the site of the mutation. The genes encoding the 3 chains of type VI collagen were also excluded on the basis of discordant inheritance. The disease in this family is therefore not the result of mutations in the genes encoding type II or type VI collagen.

Adult↗
PubMed1993

Localization of the Krabbe disease gene (GALC) on chromosome 14 by multipoint linkage analysis.

The gene responsible for Krabbe disease, an autosomal recessive disorder caused by deficiency of galactocerebrosidase (GALC), was localized by multipoint linkage analysis on chromosome 14. Eight mapped dinucleotide repeat polymorphisms were tested for linkage to GALC. Two-point linkage analysis demonstrated close linkage of GALC and D14S48, with Z = 13.69 at theta = 0. Multipoint analysis yielded strong support for this finding, with maximum likelihood for GALC located within 1 cM of D14S48. This analysis also identified markers that clearly flank the GALC locus, as the map order of D14S53-GALC-D14S45 is favored by odds greater than 10(6):1. Additional support for close linkage of GALC and D14S48 comes from the apparent linkage disequilibrium between these two loci in a consanguineous Druze community in Israel. These data localize GALC to 14q24.3-q32.1.

Chromosome Mapping↗
PubMed1989

Amplified DNA in cells of genetic melanoma of Xiphophorus.

Melanomas of genetic origin develop in interspecies hybrids of the fish Xiphophorus. Cytogenetic analyses have indicated chromosomal manifestations of amplified DNA in cells of an in vitro established cell line derived from a melanoma. We have employed strategies of differential hybridization in agarose gels to isolate and clone a portion of the amplified DNA. Amplification was about 20-fold in melanoma cells established in culture and about 10-fold in 2 out of 5 melanomas directly derived from the animal. The amplified DNA contained at least one transcription unit that is evolutionarily conserved in all vertebrates tested, including chicken, murines and man. Our results indicate that amplification of an as yet uncharacterized gene is involved in genetic melanoma of Xiphophorus.

Animals↗