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C Denniston

Publications and source records attributed to C Denniston.

At least 37 records · Page 2Linked to original sources
PubMed1985

Mitotic chiasmata, gene density, and oncogenes.

Chromosomes with regions rich in mitotic chiasmata in Bloom syndrome (1,3,6,11,12,17,19, and 22) have been compared for various parameters to similar-sized chromosomes 2, 4, 7, 10, 9, 18, 20, and 21 with the following results: (1) The number of genes localized on the test chromosomes is significantly higher (248) than that in the control chromosomes (133). (2) The number of trisomic abortions is significantly lower (45) for the test chromosomes than for the control chromosomes (140). (3) Homogeneously stained regions in neuroblastoma lie at chiasma-containing regions on chromosome arms 1p, 6p, 17q, and 19p or q. (4) The average chiasma density of regions with at least one oncogene is 2.414, whereas that of regions containing no known oncogene is 1.137; however, the difference is not statistically significant. The association of constant cancer chromosome breaks is also in the positive direction, but is not statistically significant. Our tentative conclusion is that the chiasma-rich regions which are Q-dark and early-replicating, and therefore assumed to contain active "housekeeping" genes are extended in interphase. Thus they are available for mitotic crossing-over. In the trisomic state they act as trisomy lethals, leading to early abortions. Being gene-rich they are more likely to contain oncogenes which is reflected also in their agreement with cancer breakpoints. The very high incidence of cancer in Bloom syndrome is a further indication of the possible association of cancer-related phenomena and mitotic crossing-over.

Abortion, Spontaneous↗
PubMed1983

Are human studies possible? Some thoughts on the mutation component and population monitoring.

The concept of the mutation component of a genetic trait is discussed and its relation to heritability investigated. It is found that for qualitative traits held in the population by opposing directional selection and mutation, the mutation component equals the broad sense heritability. The mutational component of a quantitative trait with an intermediate optimum is found generally to be between half and one times the (narrow sense) heritability of the character. Although more work on this matter is required, the finding of a relationship between mutation component and heritability should allow us to make better predictions regarding the likely impact of an increased mutation rate on the human population. Some statistical problems relevant to the detection of an increased mutation rate are also discussed.

Genetics, Medical↗
PubMed1981

The mutation component of genetic damage.

The mutation component, M, is a measure of the proportion of the impact of a genetic condition that is attributable to recurrent mutation. For a trait maintained by balance between mutation and directional selection, M is approximately the broad-sense heritability; for a measured character where the mean and optimum coincide, M is about half the heritability. If the narrow-sense heritability is high, the impact changes relatively rapidly with a change in mutation rate. If the narrow-sense heritability is low, M cannot be predicted, but the change in impact following a change in mutation rate, if any, is very slow.

Genetics, Medical↗
PubMed1981

Genetic polymorphism of PIF (parotid isoelectric focusing variant) proteins with linkage to the PPP (parotid proline-rich protein) gene complex.

Genetic polymorphism is found among the PIF (parotid isoelectric focusing variant) salivary proteins after separation by prolonged isoelectric focusing in pH 3.5-5.2 urea polyacrylamide slab gels subsequently stained for protein. Two PIF proteins are either present (PIF+) or absent (PIF-) from all salivas. The phenotypes are determined by autosomal inheritance of two alleles, PIF+ and PIF-. Gene frequencies in randomly collected samples show marked racial differences: among 148 whites, PIF+ is 0.66 and PIF- is 0.34; among 90 blacks, PIF+ is 0.35 and PIF- is 0.65; among 78 Chinese, PIF+ is 0.56 and PIF- is 0.44. Studies in 41 families including 129 children support the interpretation of control of PIF by a single autosomal locus. In 8 PIF+ X PIF- matings, there were 8 PIF- (6.34 expected) children. In 33 PIF+ X PIF+ matings, there were 7 PIF- (6.70 expected) children. Linkage studies indicate that PIF is closely linked to the proline-rich protein (PPP) gene complex (e.g., for six families, lod score at theta = 0.00 of PIF/Gl is 3.58). In 107 randomly collected samples from whites, PIF is strongly associated with Db (chi 2(1) = 20.02; P less than 0.0001) and Gl (chi 2(1) = 12.58; P = 0.0005) but not with Pr, Ps, Pm, and Pa proteins. These data (probably reflecting genetic disequilibrium) suggest that PIF may be closer to Db and Gl than to other identified loci of the PPP gene complex. The PPP gene complex includes at least seven genes (and probably more) that produce many acidic and basic proline-rich proteins, constituting about two-thirds of parotid salivary proteins that are thought to have important functions at the tooth surfaces.

Adult↗
PubMed1980

X chromosome constitution and the human female phenotype.

The correlations of abnormal X chromosome constitutions and the resulting phenotypes in the human female are reviewed. The following hypotheses put forward to explain these correlations are discussed in detail: (1) The damage is done before X inactivation; (2) An effect is exerted between reactivation of the X chromosome(s) and meiosis in oocytes; (3) A recessive gene(s) in hemizygous condition might be expressed in the cases in which the same X is active in all cells; (4) A change in the number of presumed active regions on the inactive X chromosomes might have an effect; (5) A position effect, in that the region Xq13-q27 has to be intact in both X chromosomes to allow normal development, may be responsible; (6) An effect during the period when cells with different inactivation patterns compete is a probability; (7) The original X inactivation may be neither regular nor random. The conclusion reached is that the phenotypic effects of a specific X chromosome aberration may be simultaneously exerted through different pathways (Tables 1 and 2). Hypotheses (2), (4), (5), and (6) are considered probable. Hypothesis (3) has been discarded, and there is very little evidence for hypotheses (1) and (7).

Adolescent↗
PubMed1980

Polymorphism of Ps (parotid size variant) and detection of a protein (PmS) related to the Pm (parotid middle band) system with genetic linkage of Ps and Pm to Gl, Db, and Pr genetic determinants.

Genetic polymorphism of the Ps (parotid size variant) proteins found in saliva is determined by autosomal inheritance of two expressed and one unexpressed allele. This hypothesis is supported by studies in 43 families including 153 children. Gene frequencies determined for 150 randomly collected salivas from whites and 101 randomly collected salivas from blacks are as follows: for whites, Ps1 = 0.598, Ps2 = 0.101, Ps0 = 0.301; for blacks, Ps1 = 0.185, Ps2 = 0.126, and Ps0 = 0.689. The electrophoretic polymorphism is manifested by apparent differences in molecular weights between Ps proteins. The Ps proteins are glycosylated and have an approximate isoelectric point of pI 8.1 as determined by isoelectric focusing in gels. We have also found in saliva the presence of a protein (PmS) which shows strong positive correlations with the presence of the smaller sized Pm (PmF) salivary protein described by Ikemoto et al. (1977). This suggested that PmS is probably part of the Pm protein polymorphic system. For randomly collected salivas from whites, the gene frequencies are PmF+ = 0.15 (N = 140) and PmS+ = 0.12 (N = 150). For randomly collected salivas from blacks, the gene frequency is PmS+ = 0.24 (N = 101). The gene frequency of PmF+ was not determined. Family studies support autosomal inheritance of PmF and PmS.

Adult↗
PubMed1980

Determining antigenic relationships on the basis of MLC testing. I. A matrix approach for listing all possible antigenic assignments.

We present an approach for determining all possible antigenic relationships among a group of individuals, on the basis of MLC results. We assume that the researcher or tissue typer has a criterion for classifying responses into positives and negatives, and that this classification has already been done for the data set being considered. Given any set of positive and negative MLC responses, our technique produces all antigenic assignments consistent with the assumption that a response occurs if and only if the stimulator has antigen(s) foreign to the responder. No genetic assumptions are made.

Antigens↗
PubMed1980

Determining antigenic relationships on the basis of MLC testing. II. Mechanical algorithms.

We describe mechanical algorithms, involving manipulations of matrices, for listing all possible antigenic relationships among individuals tested in MLC. We also describe an algorithm for determining whether an MLC result can be interpreted in line with our assumption of the preceding paper, that stimulation occurs if, and only if, the stimulator has antigen(s) foreign to the responder.

Antigens↗
PubMed1979

Position of the human X inactivation center on Xq.

In three women with a 46,XXq- chromosome constitution, the length of the deletion was expressed as the ratio of the remaining part of Xq to Xp c' over a + b. In one of them (KH) this ratio was 0.33, in another (GE) 0.59, and in the third (AP) the ratio fell between these values. The break in KH is more or less on the border of the Q-dark proximal region. A comparison with relevant X-autosomal translocations indicates that the X inactivation center lies near, but not at the border of, the Q-dark and the adjoining bright region (c and d).

Adult↗
PubMed1979

Genetic polymorphism of the major parotid salivary glycoprotein (Gl) with linkage to the genes for Pr, Db, and Pa.

Genetic polymorphism of the major glycoprotein (Gl) found in parotid saliva is determined by autosomal inheritance of one unexpressed and four expressed alleles. This hypothesis is supported by studies in 41 white families including 146 children. For 143 randomly collected salivas from whites and 82 randomly collected salivas from blacks, maximum likelihood estimates of the gene frequencies are as follows: for whites, Gl1 = 0.742, Gl2 = 0.040, Gl3 = 0.155, Gl4 = 0.017, Gl0 = 0.46; for blacks, Gl1 = 0.459, Gl2 = 0.050, Gl3 = 0.337, Gl4 = 0.044, Gl0 = 0.110. There is strong evidence for linkage of Gl/Pr (seven families, lod score at theta = 0 is 5.24) and G1/Db (eight families, lod score at theta = 0 is 4.45). The allelic products of Gl show evidence for linkage disequilibrium with the products of the Pr, Db, and Pa loci (P less than 0.0005). On the basis of varying degrees of linkage disequilibrium, Gl may be closer to Db than to Pr or Pa and on the "outside" of Db with respect to Pr or Pa. Amino acid analyses of Gl 1 and Gl 4 proteins show strong resemblances in composition to the major basic glycoprotein and the acidic proline-rich proteins of parotid saliva described by other workers. The polymorphic forms of the Gl proteins show microheterogeneity due to variability in charge and molecular weight. The electrophoretic polymorphism appears to be determined by apparent differences in molecular weights between the Gl proteins.

Alleles↗
PubMed1979

Genetic polymorphism of vitamin B12 binding (R) proteins of human saliva detected by isoelectric focusing.

Genetic polymorphism of the vitamin B12 binding (R) proteins of parotid saliva is determined by autosomal inheritance of codominant alleles. This hypothesis is supported by studies in 43 families including 152 children. For randomly collected salivas from 143 whites, 104 blacks, and 75 Chinese, gene frequencies are as follows: for whites, Rs1=0.88, Rs2=0.12; for blacks, Rs1=0.94, Rs2=0.06; for Chinese, Rs1=1.00. This genetic marker is also shared by R proteins of milk, tears, and leukocytes. In the Rs 1--2 salivary type there is less labeling of the protein products of Rs2 v. Rs1 with 57Co B12 as assessed by the intensity of the bands on the autoradiogram. There is no evidence for close linkage (theta less than 0.01) between Rs and TC II (transcobalamin II) or between Rs and salivary protein locus Pr, Db, Gl, or Ps.

Carrier Proteins↗
PubMed1978

Mitotic chiasmata in human diplochromosomes.

Three placental tissue cultures of spontaneous human abortions showed an unusually high frequency of metaphases with diplochromosomes. In 62 such cells, nine configurations were interpreted as mitotic chiasmata between the two sister chromosomes of a diplochromosome. One U-type exchange between two sister chromosomes was also found. This differs significantly from the 1 : 1 ratio of adjacent and alternate exchanges in translocations, thus supporting the idea that mitotic chiasmata are in principle different from chromatid translocations. The hypothesis is put forward that the frequency of homologous exchanges is determined by the intimacy of pairing which ranges from meiotic pairing through sister chromatid association, through sister chromosome association in diplochromosomes to accidental pairing of homologous regions in diploid cells.

Abortion, Spontaneous↗
PubMed1978

An incorrect definition of fitness revisited.

I have attempted to show that a certain mistaken definition of fitness, which surfaces occasionally, may turn out to have some merit. No claim is made that it is an improvement on, or should replace, the conventional definition of fitness; but it is different and has its own validity. Its generality is intriguing, its application is not limited either to selection or one locus models, and it may be easier to measure experimentally.

Biological Evolution↗
PubMed1977

Nonpairing of the X and Y chromosomes in the spermtocytes of BDF1 mice.

In the hybrid mouse strain BDF1, some 35--40% of spermatocytes had unpaired X and Y choromosomes in stages ranging from diplotene to first meiotic metaphase. This phenomenon varied significantly from mouse to mouse. In pooled material from Swiss Albino and CF1 mice, the corresponding frequency was 5.7%. In C57 BL/6 mice, one of the parent strains of BDF1 mice, the X and Y were separate in 7.7% of the spermatocytes. Based on the behavior of the X and Y in the BDF1 strain, it is concluded that they do not pair, rather than initially pairing and then precociously separating. The factor interfering with the pairing of the X and Y does not affect the autosomes; possibly it is an incompatibility of the two sex chromosomes, which come from different inbred lines.

Animals↗
PubMed1976

A possible active segment on the inactive human X chromosome.

An idic(Xp--) in which the two X chromosomes are attached short arm to short arm, and which thus has two b regions (the Q-dark segment next to the centromere on Xp) between the inactivation centers, assumed to be situated on the Q-dark region next to the centromere on Xq, showed 63.8% bipartite Barr bodies as compared with 22.2% formed by idic(Xq--). In addition, the mean distance of the two parts of the Barr bodies in the fibroblasts of a patient with idic(Xp--) is significantly greater than in the cases with one or no b region. Contrary to the other patients with abnormal X chromosomes, the buccal cells of a woman idic(Xp--) showed a number of bipartite Barr bodies. -- To explain these observations we have put forward the hypothesis that the b region on the Xp always remains active and thus, when the rest of the chromosome forms a Barr body, this segment is extended, allowing the two parts of the X chromatin to get farther apart and at the same time increasing the percentage of bipartite bodies.

Female↗
PubMed1976

A note on serological interpretations.

This paper deals with the interpretation of binary serological data. It attempts to render exact and answer two questions: 1) What are all the serological interpretations of a given set of data? 2) How can different interpretations be distinguished serologically? It is hoped that the formal analysis of serology presented herein will prove to be helpful to those working with complex immunological systems.

Antibody Specificity↗