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Biomedical subjects

D T Bishop

Publications and source records attributed to D T Bishop.

156 records · Page 9Linked to original sources
PubMed1983

A model for restriction fragment length distributions.

We develop here a model for restriction fragment length distributions based on DNA dimer frequencies in humans. Mean fragment lengths are computed for known restriction enzymes. This model is tested using data from the hybridization of a series of arbitrary single-copy DNA probes screened with a set of restriction enzymes. The fit to the model appears good. We apply the model to the problem of how much DNA is scanned by a set of enzymes. This result is then further applied to optimizing the search for insertion/deletion DNA-polymorphisms.

Base Sequence↗
PubMed1983

Linkage analysis in dominant optic atrophy.

A kindred of German descent was studied for dominant optic atrophy, type Kjer (McKusick catalog no. 16540). One hundred twenty-three family members were examined clinically, and 36 affected, 81 normal, and six uncertain members were ascertained. Twenty-seven markers were analyzed for 121 members. The maximum lod score obtained was 2.0 at theta = .18 for linkage between the Kidd locus and dominant optic atrophy. Twenty-eight offspring were informative with 2-generation data. There was insufficient information for the acid phosphatase locus to aid gene localization. These data suggest that the locus for dominant optic atrophy is on chromosome 2.

Chromosome Mapping↗
PubMed1982

Hereditary hemochromatosis. Analysis of laboratory expression of the disease by genotype in 18 pedigrees.

Tight linkage between the hemochromatosis locus and the HLA region permits determination of genotype in members of hemochromatosis pedigrees. To determine if simple laboratory measures of iron metabolism could predict the affected genotype without the need for HLA typing, we studied seven measures of iron metabolism: serum iron concentration, total iron-binding capacity, per cent saturation of transferrin, serum ferritin concentration, deferoxamine-induced urinary iron excretion and hepatic iron concentration evaluated by both chemical and histological methods. Discriminant analysis showed a per cent saturation of transferrin above 62% to be the best simply-measured indicator of the affected genotype: homozygosity is accurately predicted in 92% of the cases. The logarithmic transform of serum ferritin concentration was only 71% accurate. Pedigree analysis estimated the frequency of the hemochromatosis gene at 0.069 +/- 0.020 with a recombination probability of 0.015 +/- 0.015 with the HLA region. This corresponds to a heterozygote frequency of 0.13 and a disease frequency of 0.005.

Age Factors↗
PubMedDate not supplied

Alternative explanations for normal variability in antithrombin-III levels.

Data collected in a study of ATIII deficiency also suggested familial variability of blood clotting times amongst genotypically normal individuals. A study of this variability under a variety of models demonstrates a clear age effect and within sibship similarity. There is also a clear parental effect, which could be either environmental or genetic. Even when parental effects are taken into account there remains some excess similarity between sibs, but the increase in log-likelihood provided by this component is no longer highly significant.

Analysis of Variance↗
PubMedDate not supplied

Comparison of enzyme mismatch cleavage and chemical cleavage of mismatch on a defined set of heteroduplexes.

Two mutation detection methods based on the cleavage of mismatched heteroduplexes were compared and evaluated. These techniques, chemical cleavage of mismatch (CCM) and enzyme mismatch cleavage (EMC), have the advantages over other available methods of being able to detect and localize mutations in relatively large fragments of DNA (> or = 1 kb). We have constructed clones that enable us to create heteroduplexes of 500 bp, 1 kb, and 1.5 kb and have assessed each of the methods over a range of criteria. Both were able to detect and localize all four types of single-base mismatch and insertion/deletions of 1-5 bp. Whereas EMC was efficient at detection of insertion/deletions in a broad size range of fragments and has the advantage over CCM of using no hazardous chemicals, in our hands it has not been sufficiently robust that we felt confident to consider it for diagnostic use in its present form. CCM using hydroxylamine was efficient over the entire range of fragment sizes tested and using potassium permanganate with tetraethylammonium chloride was efficient up to 1 kb.

Base Pairing↗
PubMedDate not supplied

Methodological issues in linkage analyses for psychiatric disorders: secular trends, assortative mating, bilineal pedigrees. Report of the MacArthur Foundation Network I Task Force on Methodological Issues.

A Task Force was assembled to address three data problems in genetic linkage analyses: (1) a secular trend, e.g. cohort effect; (2) positive assortative mating, and (3) bilineal pedigrees. All are cited as reasons for failure to replicate genetic linkage reports. However, we knew of no work demonstrating that these factors could invalidate or bias linkage analyses, nor that they were complications (e.g., variable age of onset). The Task Force concluded that these factors can reduce the power of linkage analyses and result in bias in the estimate of the recombination frequency due to the fact that they represent 'noise' in the system. There was little evidence that the three factors would invalidate a linkage analysis or be directly responsible for negating a linkage finding.

Cohort Effect↗