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S A Seuchter

Publications and source records attributed to S A Seuchter.

14 recordsLinked to original sources
PubMed1994

Population data and forensic efficiency values for the STR systems HumVWA, HumMBP and HumFABP.

Population studies were carried out on Caucasians from north-west Germany using the short tandem repeat (STR) systems HumVWA (locus: 12p12-12pter), HumMBP (locus: 18q23-pter) and HumFABP (locus: 4q28-q31). After electrophoresis 9 alleles could be identified for HumVWA in a sample size of 321 unrelated individuals and 4 alleles were found for HumFABP in 106 individuals. For HumMBP-A 10 alleles and for HumMBP-B 7 alleles and 1 intermediate allele were determined in a sample size of 143 individuals. No deviations from Hardy-Weinberg equilibrium could be observed. In a small family study (HumVWA-n = 129; HumMBP-n = 59; HumFABP-n = 48) no new mutations could be found for HumMBP-A and HumFABP whereas 2 mutations were found in HumMBP-B and one mutation in HumVWA. Positive results could be obtained from 1 ng-20 pg (HumVWA, HumFABP) and 1 ng-100 pg (HumMBP) template DNA.

Alleles↗
PubMed1994

Two-locus disease models with two marker loci: the power of affected-sib-pair tests.

Recently, Schork et al. found that two-trait-locus, two-marker-locus (parametric) linkage analysis can provide substantially more linkage information than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al. do not expect that their approach will be applied in an initial genome scan. Further, the specification of a suitable two-locus segregation model can be crucial. Affected-sibpair tests are computationally simple and do not require an explicit specification of the disease model. In the past, however, these tests mainly have been applied to data with a single marker locus. Here, we consider sib-pair tests that make it possible to analyze simultaneously two marker loci. The power of these tests is investigated for different (epistatic and heterogeneous) two-trait-locus models, each trait locus being linked to one of the marker loci. We compare these tests both with the test that is optimal for a certain model and with the strategy that analyzes each marker locus separately. The results indicate that a straightforward extension of the well-known mean test for two marker loci can be much more powerful than single-marker-locus analysis and that is power is only slightly inferior to the power of the optimal test.

Alleles↗
PubMed1993

The effect of misspecifying allele frequencies in incompletely typed families.

To examine the effect of a misspecified marker allele frequency, the segregation of a marker unlinked to Alzheimer's disease was simulated for the typed members of the GAW8-FAD4 pedigree. Lod scores were calculated for different assumed marker allele frequencies. The results show that a misspecification of marker frequency can lead to spuriously high lod scores. The affecteds-only method for linkage analysis is even more sensitive in regard to marker frequency misspecification. Therefore, we recommend estimation of marker allele frequencies from the actual family data. The simple estimator we considered in this paper seems to be sufficient.

Alleles↗
PubMed1993

The haplotype-relative-risk (HRR) method for analysis of association in nuclear families.

One major problem in studying an association between a marker locus and a disease is the selection of an appropriate group of controls. However, this problem of population stratification can be circumvented in a quite elegant manner by family-based methods. The haplotype-relative-risk (HRR) method, which samples nuclear families with a single affected child and uses the parental haplotypes not transmitted to that child as a control individual, represents such a method for estimating the relative risk of a marker phenotype. In the special case of a recessive disease, it was already known that the equivalence of the HRR method with the classical relative risk (RR) obtained from independent samples holds only if the probability theta of a recombination between marker and disease locus is zero. We extend this result to an arbitrary mode of inheritance. Furthermore, we compare the distribution of the estimators for HRR and RR and show that, in the case of a positive linkage disequilibrium between a marker and disease allele, the distribution of the estimator for HRR is (stochastically) smaller than that for RR, irrespective of the recombination fraction. The practical implication of this result is that, for the HRR method, there is no tendency to give unduly high risk estimators, even for theta > 0. Finally, we give an expression for the standard error of the estimator for HRR by taking into account the nonindependence of transmitted and nontransmitted parental marker alleles in the case of theta > 0.

Alleles↗
PubMed1992

Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.

In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0 alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQ0 and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4Q0 alleles being the decisive factors increasing susceptibility to SLE.

Alleles↗
PubMed1991

Testing for association in SLE families.

Systemic lupus erythematosus (SLE) is a complex disease which is partly determined by genetic factors which influence susceptibility to the disease phenotype. In this association study we try to define the high risk haplotypes which are responsible for this disease, together with other environmental factors. In many other association studies a set of SLE patients is compared to a set of controls. The basic assumption about the underlying population is that the disease and control sample should originate from the same genetic population, which is not always completely satisfied in many studies. Therefore, we analyse our family data by applying the Haplotype Frequency Difference (HFD) Method, which constructs its internal control group from those haplotypes not transmitted to the affected individual. Results partially conform with other studies, showing that the haplotypes B8 DR3 as well as B7 DR2 have a high positive association with SLE. When the DR locus was analyzed alone, we found besides the alleles DR2 and DR3 a negative association for DR1, DR5, and DR6.

Adult↗
PubMed1990

Gene of type II autosomal dominant retinitis pigmentosa maps on the long arm of chromosome 3.

Linkage analysis has been performed on a large Australian family segregating for the autosomal dominant form of retinitis pigmentosa (ADRP). The majority of patients had no subjective symptoms of night blindness until their second decade and good visual acuity until late in life. The disease in this family has been classified as Type II ADRP according to the subdivisions provided by both Massof and Finkelstein and Fishman and colleagues. Linkage (Omax:0.08 at Zmax:4.78) is here demonstrated between the disease locus and D3S47 (a marker locus on the long arm of chromosome 3), which showed in an earlier study very close linkage without recombination to the disease locus in an Irish pedigree with a clinically more severe and early onset (Type I) ADRP.

Chromosome Aberrations↗
PubMed1989

Applying expert system techniques to human genetics.

Although expert systems have been developed in a variety of medical areas, there has been very little application of expert system techniques to the field of human genetics. The purpose of the research project described in this paper was (1) to experiment with different types of knowledge representation for data and knowledge structures in human genetics and (2) to explore the applicability of different inference mechanisms for various genetic problems. We present an object-oriented and a fact-based model for the representation of genealogical information and describe two prototype systems.

Algorithms↗
PubMed1989

The dysplastic melanocytic nevus: a prevalent lesion that correlates poorly with clinical phenotype.

We estimated the prevalence of persons with histologic dysplasia in at least one of two nevi examined by biopsy to be 53% in Utah's caucasians. This apparently high prevalence indicates that such lesions may represent a normal variant of a melanocytic nevus, perhaps those in the process of active proliferation. Regardless of the apparent ubiquity of these lesions, examination of biopsy specimens led to a grading scheme of histologic dysplasia that may reflect chronologic stages in the neoplastic development of melanocytic nevi. Comparison of these histologic findings with the clinical examination yielded the unexpected result that dysplasia and lesion size are independent of each other. Lesions 3 mm in diameter or smaller were as likely to be dysplastic as those much larger. There was, however, a statistically significant relationship between histologic dysplasia of a nevus examined by biopsy and the person's total number of melanocytic lesions. This finding indicates that the pathology grading scheme may be useful. The high prevalence of dysplastic nevi dilutes the clinical significance of a dysplastic nevus as an isolated finding and thereby lessens the importance of pathologic findings in the diagnosis of dysplastic nervus syndrome.

Adolescent↗
PubMed1988

HGDBMS: a human genetics database management system.

Human genetics research involves a large number of complex data sets naturally organized in hierarchical structures. Data collection is performed on different levels, e.g., the project level, pedigree level, individual level, and sample level. Different aspects of a study utilize different views of the data, requiring a flexible database management system (DBMS) which satisfies these different needs for data collection and retrieval. We describe HGDBMS, a comprehensive relational DBMS, implemented as an application of the GENISYS I DBMS, which allows embedding the hierarchical structure of pedigrees in a relational structure. The system's file structure is described in detail. Currently our Melanoma and Chromosome 17 map studies are managed with HGDBMS. Our initial experience demonstrates the value of a flexible system which supports the needs for data entry, update, storage, reporting, and analysis required during different phases of genetic research. Further developments will focus on the integration of HGDBMS with a human genetics expert system shell and analysis programs.

Computer Systems↗
PubMedDate not supplied

Linkage analysis in nuclear families. 1: Optimality criteria for affected sib-pair tests.

The affected sib-pair method can be applied to investigate linkage between a marker locus and a disease. Several statistics have been proposed to test if the observed pattern of marker alleles shared identically by descent (ibd) is compatible with the null hypothesis of no linkage. Here, we consider different optimality criteria for sib-pair linkage tests. While for recessive inherited diseases the mean test is found to be uniformly (in theta) most powerful, it can also be shown that, irrespective of the mode of inheritance, the mean test is the locally optimal test.

Chromosome Mapping↗
PubMedDate not supplied

Linkage analysis in nuclear families. 2: Relationship between affected sib-pair tests and lod score analysis.

It is believed that the main advantage of affected sib-pair tests is that their application requires no information about the underlying genetic mechanism of the disease. However, here it is proved that the mean test, which can be considered the most prominent of the affected sib-pair tests, is equivalent to lod score analysis for an assumed recessive mode of inheritance, irrespective of the true mode of the disease. Further relationships of certain sib-pair tests and lod score analysis under specific assumed genetic modes are investigated.

Data Interpretation, Statistical↗