Showing papers by "Richard S. Spielman published in 1981"

Genetics of red cell COMT activity: analysis of thermal stability and family data.

Abstract: Previous studies have shown that the activity of human red cell catechol-O-methyltransferase (RBC COMT) is significantly correlated in sibs, that the population distribution is bimodal, and that RBC COMT from individuals with low activity is more thermolabile than that from individuals with high activity. These observations and additional data from family studies are consistent with the hypothesis that RBC COMT activity is controlled by two alleles at an autosomal locus [Weinshilboum and Raymond, 1977], giving rise to genotypes with different but overlapping activity distributions. In the present study, this hypothesis has been explored with various types of analyses. Given the assumption of Hardy-Weinberg genotype frequencies, we find that the population distribution of RBC COMT activity is explained much better by codominant or “intermediate” inheritance than by either dominant or recessive inheritance. The intermediate genetic model has also been used to analyze the data of Scanlon et al [1979] on thermal inactivation of RBC COMT in a random sample of blood donors. Hypothesis tests based on this analysis confirm the conclusion of Scanlon et al that individuals with different COMT genotypes differ in the thermostability of their RBC COMT. Using the RBC COMT activities of low-activity probands and their parents, we have derived the expected distribution of activity among the proband's sibs on the assumption of three genotypes in Hardy-Weinberg equilibrium in the population. The fit of this expected distribution to that observed is excellent, supporting the genetic model.

Estimation of genetic variation at the DNA level from restriction endonuclease data.

Abstract: We consider the estimation of the genetic variation in a natural population when the data are obtained by the use of restriction endonucleases. Under the restriction endonuclease technique, a particular DNA segment is considered and cut wherever a recognition sequence appropriate to the endonuclease occurs. We consider data generated when a random sample of homologous DNA segments is treated in this way with one or a battery of restriction endonucleases. The numbers and sizes of the fragments that result indicate the locations and the frequencies of the recognition sequence (or, with a battery of restriction endonucleases, of each recognition sequence). These frequencies in the sample form the basis for an estimate of the amount of genetic variation in the population.

Monoclonal rat anti-MHC alloantibodies detectHLA-linked polymorphisms in humans

Abstract: Two monoclonal rat anti-MHC alloantibodies detect a polymorphic determinant expressed on the peripheral lymphocytes of normal human donors. The pattern of cytotoxicity observed with these antibodies correlated with theHLA type of the individual; no HLA-A-locus specificities showed significant associations, and all of the HLA-B-locus specificities showing significant association were members of the Bw6 supertype. Family studies established that the determinant detected by the monoclonal antibodies is linked toHLA. These studies therefore provide an alternative basis for the production of monoclonal antibodies to polymorphic HLA determinants based on the conservation of polymorphic MHC determinants between man and rats.