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L A Corey

Publications and source records attributed to L A Corey.

At least 37 records · Page 2Linked to original sources
PubMed1987

Does the PI polymorphism alone control alpha-1-antitrypsin expression?

Whether genetic factors other than the protease-inhibitor (PI) polymorphism itself contribute to variation in alpha-1-antitrypsin is of both theoretical and practical interest. We have measured the quantity of alpha-1-antitrypsin (by an immunoturbidometric assay) and its activity (by assaying elastase inhibitory capacity [EIC]) in 583 individuals from 114 twin kinships who were also typed for PI by isoelectric focusing. Models of variation were fitted directly to the raw observations by a maximum-likelihood method. Specification of phenotypic means led to highly significant improvements in fit over models including only individual environment variance and additive genetic variance. The 29 phenotype means could also be described as the appropriate additive combinations of the 12 allelic effects. Only small improvements in fit could then be obtained by addition of polygenic components of variance. We conclude that nearly all genetic variation in alpha-1-antitrypsin quantity and activity can be explained by detectable variation at the PI locus and that this variance is largely additive. Bivariate analysis of alpha-1-antitrypsin and EIC revealed marginal evidence for differences in specific activities of molecules coded by different PI alleles. The correlation between environmental deviations for the two measures was only .63, which may reflect, in part, the rather low reliability of the assays and account for the modest heritabilities (less than .5) of the two measures. An intriguing finding was the presence of significant differences in E1 variance for different PI types, suggesting that different phenotypes have differing capacities to react to environmental challenges.

Adolescent↗
PubMed1986

Testing for developmental changes in gene expression on resemblance for quantitative traits in kinships of twins: application to height, weight, and blood pressure.

Height, weight, and blood pressure measurements on identical and fraternal twins and their families were analyzed to assess the degree to which genetic effects may change with age. The blood pressure data were based on the total sample of 1,767 individuals, while height and weight were available on 1,640 individuals in 204 monozygotic twin kinships. The results of testing alternative hypotheses about developmental changes in gene expression indicate that different mechanisms may be operative for these traits. While there was no evidence that developmental effects are a significant source of the observed variation in systolic or diastolic blood pressure, there was strong evidence that genetically determined developmental changes are an important factor in the determination of body weight. Age-related changes in weight appeared to be best explained by the cumulative developmental effects of a single set of genes, rather than by the expression of new genes at different stages of development.

Adolescent↗
PubMed1985

Nucleolar organizer region variants as a risk factor for Down syndrome.

An unusual nucleolar organizer region (NOR) heteromorphism was noted among 13 of 41 parents in whom nondisjunction leading to trisomy 21 was known to have occurred. In contrast, only one of these double NOR (dNOR) variants was found among the 41 normal spouses and none were seen among 50 control individuals. In two dNOR(+) families, a second child with trisomy 21 was conceived. In both families, the extra chromosome in each child was contributed by the parent who carried the dNOR variant and resulted from a recurrent meiosis I error. Our data suggest that the dNOR heteromorphism may play a role in meiotic nondisjunction and could be associated with as much as a 20-fold increased risk for having offspring with trisomy 21.

Child↗
PubMed1984

Influence of diabetes mellitus heredity on susceptibility to coxsackievirus B4.

Using the criteria of virus susceptibility as defined by the 50 percent lethal dose response and the percent cumulative mortality response it was shown that the diabetic mutation db, located on chromosome 4, exerted a particular influence on the host response to CB4 challenge. Neither the yellow obese mutation Ay on chromosome 2 nor the misty coat color mutation located one centimorgan from the db mutation had the same effect on CB4 response. The obese diabetic mutation ob located on chromosome 6 appeared to enhance susceptibility to CB4. However, the high susceptibility of the inbred C57BL/6J line on which the ob mutation is found was apparently a significant contributing factor to the ob mutant high virus susceptibility. The response to CB4 was also a useful criteria to discern differences in the genetic background of closely related inbred lines. Based on the CB4 LD50 values the C57BL/6J inbred line was the most susceptible while the C57BL/Ks inbred line was the most resistant. However, using the percent cumulative mortality response as an index of host resistance, the C57BL/KsJ was the most susceptible and the C57BL/Ks the least. These findings further support the thesis that genetic predisposition to diabetes mellitus, as characterized by the mutation db on chromosome 4 is associated with a particular susceptibility and host response to coxsackie-virus B4. It also illustrates that under specific conditions, comparison of the response to virus challenge can be used as an indicator of genetic differences between closely related inbred lines.

Animals↗
PubMed1983

A causal analysis of birth weight in the offspring of monozygotic twins.

Data were collected on the birth weights of 1,694 offspring of 385 sets of twins including 108 male and 131 female monozygotic pairs. To resolve the influence of birth order from the genetic, environmental, and maternal effects on birth weight, we analyzed the full-sib and maternal and paternal half-sib correlation matrices for birth orders one to five using a causal model that assumed each live-born child had an influence on the weight of the subsequent birth. Prenatal maternal influences explained 40% of the variation in birth weight of the first-born child and 52% for the fifth child; genetic or environmental factors common to monozygotic twins accounted for 72% of this effect, while environmental variables unique to individual mothers were responsible for the remaining 28%. The inclusion of a birth-order parameter resulted in a highly significant improvement in the goodness of fit of the causal model such that by the fifth child, 46% of the maternal variation could be attributed to the cumulative effects of previous live births.

Adult↗
PubMed1981

Quinacrine mustard and nucleolar organizer region heteromorphisms in twins.

Patterns of NOR activity in 640 metaphase spreads from twelve monozygotic (MZ) and eight dizygotic (DZ) twin pairs were studied to evaluate the heritability of this chromosomal heteromorphism. NORs were stained by a modification of the Ag-AS technique and counterstained with quinacrine mustard dihydrochloride to facilitate chromosome identification and assess their value in zygosity determination. In this study, all karyotypes were read blind with respect to zygosity and pair membership. A discriminant function analysis of pair score differences in MZ and DZ twins revealed that, in our sample, the probability of accurately determining zygosity with NOR scores was 0.93 and with QFQ scores was 0.99. We conclude that NOR and QFQ scores are highly heritable and of great value in zygosity determination. Data were collected from 687 metaphase spreads on the frequency with which an acrocentric chromosome was found in a satellite association. A significant correlation was found between this frequency and the degree of Ag-AS stain of the NOR. This study, therefore, confirms previous results showing that a high degree of NOR activity is found in those chromosomes most often involved in satellite associations.

Adolescent↗
PubMed1981

A genetic analysis of taste threshold for phenylthiocarbamide.

Taste threshold for phenylthiocarbamide (PTC) was measured in 393 offspring from the families of 85 monozygotic (MZ) twin pairs. PTC scores were bimodally distributed with modes at one and eight and the antimode at five. Because of the non-normality of the distribution, a jackknife procedure was used to obtain 95% confidence intervals for the estimates of genetic, maternal, and environmental parameters. Analyses which assumed no epistasis and which included additive genetic effects revealed that 37.9% of the observed variation in PTC threshold was due to additive genetic effects, 16.6% was due to dominance effects, 14.2% was due to maternal effects, 13.7% was due to a common sibship environment, and 17.6% was due to random environmental effects, yielding a broad sense heritability of 0.55 for the threshold ability to taste PTC. Analyses which did not include additive genetic effects revealed 26.6% of the observed variance was due to dominance effects, 23.6% to maternal effects, and 49.8% to environmental effects at the 0.67 confidence levels, but that environmental factors accounted for 72.4% and dominance effects for 23.6% of the observed variation at the 95% level.

Adolescent↗
PubMed1981

Determinants of ridge counts in MZ twin kinships.

The inheritance of total ridge count (TRC) was studied in 967 individuals from the families of 111 pairs of MZ twins. The sample included data on 47 male half-sibships with 227 offspring and 64 female half-sibships with 306 offspring. The males in this sample had a mean ridge count of 135 +/- 2 and the females a mean ridge count of 124 +/- 2. The distribution of scores for females showed evidence for significant skewness. For this reason, prior to the analysis, the data were corrected for sex and adjusted to normality using a power transformation. Nested analyses of variance were performed on the ridge counts from male and female half-sibships separately to derive estimates of among, between, and within-variance components. These estimates were then used in a nonlinear least squares program to estimate genetic and environmental parameters and to determine the goodness of fit of various models. A model which included additive genetic and dominance effects could not be rejected (P = 0.67) but did not fit the data as well as a simple additive genetic-random environmental model (P = 0.81). The addition of maternal effects to the later model also provided a satisfactory fit (P = 0.68). However, there were no improvement in the goodness of fit over the simple model, and estimated magnitude of the maternal effect was not significantly different from zero.

Analysis of Variance↗
PubMed1980

Data from kinships of monozygotic twins indicate maternal effects on verbal intelligence.

Familial resemblance in intellectual skills is well documented, but its interpretation is a source of continuing controversy. The critical problem is that a family's shared genes are confounded with its shared experiences, and controls possible in animal research (selective mating, cross-fostering, and uniform or randomised environments) do not directly apply to human subjects. Conventional twin and family methods reveal substantial genetic variance in intelligence quotient (IQ) test scores, but the same methods also document significant environmental influences. Research designs which can identify the nature of these environmental factors may effect progress in the 'IQ debate' (ref. 1). The families of monozygotic (MZ) twins provide a new research design which permits a unique assessment of maternal influences in quantitative traits. We describe here initial applications of the design to verbal IQ, with results suggesting that maternal effects significantly contribute to familial similarity in verbal intelligence.

Adolescent↗
PubMed1980

A study of dietary intake in adult monozygotic twins.

As a part of a study of the dietary habits of monozygotic twins, a nutrition survey including a 24-hour dietary recall interview and a three-day dietary diary was conducted on the members of 15 male and 13 female pairs of identical Caucasian twins ranging from 25 to 61 years of age. In this study, overall mean caloric, protein, fat, and carbohydrate intake of males was significantly greater than females. Members of male twin pairs also tended to be more similar than female twins in mean intake of all major nutrient groups. In general, the observed differences in overall intake between males and females were maintained even after adjustment of body weight. Male twins were characterized by greater similarity in intake of sodium and potassium; however, there was no consistent difference in the degree of correlation in intakes of members of male and female twins for either iron, calcium or phosphorus.

Adult↗
PubMed1980

A model for the analysis of mate selection in the marriages of twins: application to data on stature.

Analysis of the multiple correlations in body height within a sample of 117 monozygotic twin pairs and their spouses confirmed the existence of a high degree of assortative mating. However, the data also revealed an underlying asymmetry in the mate selection process. With respect to height, male twins were more selective than were members of female pairs, and among male twin pairs, those who were intermediate in height appeared to make the greatest contribution to the observed pattern of nonrandom mating. Because of their magnitude and potential asymmetry, the effects of phenotypic correlations between the spouses of related individuals must be correctly specified in any rigorous quantitative genetic analysis that extends beyond the nuclear family unit.

Body Height↗
PubMed1979

Effects of type of placentation on birthweight and its variability in monozygotic and dizygotic twins.

Birthweight was measured on 188 monochorionic monozygotic, 54 dichorionic monozygotic, 102 like-sexed dizygotic, and 94 unlike-sexed dizygotic liveborn twin pairs. Overall, males were found to be significantly heavier than females. These differences were not significant, however, when birthweights were compared within zygosity/chorion-type categories. Males were also characterized by a slightly greater overall total variance. Comparisons of intrapair variation of monochorionic and dichorionic monozygotic twins revealed significant differences between monochorionic pairs and dichorionic separate pairs and no significant differences between monochorionic pairs and dichorionic fused pairs. The results of this study suggest that placental proximity may have as important an influence on variation in birthweight as does the presence or absence of vascular anastomoses.

Birth Weight↗