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R C Elston

Publications and source records attributed to R C Elston.

At least 19 recordsLinked to original sources
PubMed1979

Possible linkage between alpha-haptoglobin (Hp) and depression spectrum disease.

Depression spectrum disease is an unipolar depressive illness in which at least one member of the family has unipolar depression and at least one other first degree relative has alcoholism and/or antisocial personality; using this definition, 14 depression spectrum disease families are studied. Assuming, among other things, that variability in age of onset is environmentally caused and lognormally distributed, segregation analysis shows that the data are compatible with the dichotomy of 'affected' versus 'not affected' being due to an autosomal dominant gene. A simple environmental hypothesis in which the transmission of the illness does not depend upon the parents' type could be rejected (p less than 0.001). Linkage analysis is performed by the method of maximum likelihood, taking the best fitting Mendelian model found in the segregation analysis. The results show virtually no evidence of linkage between depression spectrum disease and C3, but suggestive evidence (lod score = 1.03) of linkage between depression spectrum disease and alpha-haptoglobin (both these linkages were previously suggested by significant results in sib-pair analyses).

Adolescent↗
PubMed1979

Segregation and linkage analyses of dopamine-beta-hydroxylase activity.

Dopamine-beta-hydroxylase (DBH) activity in serum was measured by spectrophotometric methods in 95 persons of a large family (HGAR 2), along with 27 polymorphic markers from blood, urine and saliva. The distribution of DBH activity, after appropriate transformation and age adjustment, showed a significantly better fit to a mixture of two normal distributions than a single normal distribution. Pedigree segregation analyses showed evidence of a possible major gene governing low levels of DBH activity, segregating in this family in a recessive fashion. Linkage analyses between that major locus and the 27 polymorphic markers showed no significant lod scores favoring linkage. The highest lod score obtained was 0.81 with Lp at zero recombination fraction. In addition, published data on DBH activity measured by radiochemical assays on 22 families with 161 members were reanalyzed as a quantitative trait, with appropriate correction for ascertainment bias. The results were similar to that of HGAR 2, corroborating the existence of a major locus for DBH activity.

Adult↗
PubMed1979

Genetics of classic von Willebrand's disease. II. Optimal assignment of the heterozygous genotype (diagnosis) by discriminant analysis.

In classic von Willebrand's disease (vWd), assignment of the heterozygous genotype for genetic studies and diagnosis for clinical purposes (which are not exactly the same) are formidable problems. We have pointed out in the first report in this series that almost 50% of the members of two large kindred who transmitted this disease, and were therefore heterozygous, were scored as normal by the usual tests of hemostasis. This report describes how this large proportion can be significantly reduced by application of discriminant analysis. Using linear discriminants in three variables--coagulation factor VIII (VIII:C), factor-VII-related antigen (VIIIR:Ag), and the ristocetin cofactor related to factor VIII (VIIIR:WF)--we were able to classify as heterozygous more than 80% of the transmitters in the two large kindred. It was of particular interest that the four parents of two related vWd homozygotes could be scored as heterozygous by discriminant analysis even though all their laboratory tests were within the normal ranges.

Adult↗
PubMed1979

Sampling considerations in the gathering and analysis of pedigree data.

A general expression for the likelihood of a set of phenotypic observations on a randomly sampled pedigree, suitable for a wide variety of genetic models, has been previously modified to allow for independent ascertainments via probands. In this paper, further allowance is made for the fact that a pedigree usually contains some individuals who, whatever their phentoype, could never be probands, and we derive the limiting form of the likelihood appropriate for single ascertainment. The case when the sampling frame is ill-defined is discussed, and suggestions made for how to proceed in such a case.

Genetic Techniques↗
PubMed1979

Major gene analysis of quantitative variation in blood clotting factor X levels.

Blood clotting factor ten (X) levels measured in 149 people in six pedigrees were found to fit a mixture of normal distributions. No environmental effect could be identified to account for the wide separation in the means of these distributions. Pedigree analysis reveals that the data are compatible with an autosomal, one locus, two allele genetic model affecting factor X activity. Goodness of fit tests suggest that the allele for low levels of factor X is dominant, though on the basis of likelihood tests, mean heterozygote levels are different from mean homozygote levels. A similar bimodal distribution for factor X levels observed previously in a separate sample of 207 young men, indicated that the proposed dominant allele has an estimated population gene frequency of .53. The earlier estimate is remarkably similar to that obtained with the currently ascertained pedigrees. The postulated major gene accounts for more than half of the variation in factor X levels.

Alleles↗
PubMed1979

Multifactorial genetic models for quantitative traits in humans.

Quantitative traits measured in human families can be analyzed to partition the total population variance into genetic and environmental components, or to elucidate the genetic mechanism involved. We review the estimation of variance components directly from human pedigree data, or in the form of path coefficients from correlations between pairs of relatives. To elucidate genetic mechanisms, a mixed model that allows for segregation at a major locus, a polygenic effect and a sibling environmental correlation is described for nuclear families. In each case appropriate likelihoods are derived as a basis, using numerical maximum likelihood methods, for parameter estimation and hypothesis testing. A general model is then described that allows for several familial sources of environmental variation, assortative mating, and both major gene and polygenic effects; and an algorithm for calculating the likelihood of a pedigree under this model is indicated. Finally, some of the remaining problems in this area of biometric analysis are pointed out.

Genetic Variation↗
PubMed1978

The malignancy of dementias.

Sruvival times were determined for 982 patients admitted over a ten-year period to the Geneva Psychiatric Clinic. Patients with dementia had one-third the life expectancy of controls. Among patients classed as having Alzheimer disease, the longest survival times were in those with neurofibrillary tangles involving the neocortex, while those lacking this anatomical abnormality had the shortest survival times. Except for women with Alzheimer disease, patients with dementia had less than 10% life expectancy from the time of their admission to the clinic compared to the life expectancy of Geneva's population.

Aged↗
PubMed1978

A genetic study of schizophrenia pedigrees. II. One-locus hypotheses.

One-locus models have been fitted to two sets of two-generational families, studied by Kallmann because each contained a schizophrenic twin proband; in one set each twin proband was in the nuclear group, in the other in the peripheral group. Allowing for a lognormal age of onset distribution and a dependence of ascertainment probability on age of onset, the following hypotheses were tested and rejected: ascertainment probability is a noncurvilinear function of age of onset on a log-log scale; the transmission of schizophrenia is via one Mendelian locus, and the transmission of schizophrenia is independent of parental type. The last hypothesis is more likely than one-locus Mendelian inheritance, but it too must be rejected.

Alleles↗