bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic segregation analysis of red blood cell (RBC) histamineN‐methyltransferase (HNMT) activity
Authors: Price R. Arlen , Scott Mary C. , Weinshilboum Richard M.
Published: June 2005

Methylation is an important pathway in the biotransformation of many drugs, neurotransmitters, and xenobiotic compounds. HistamineN‐methyltransferase (HNMT) catalyzes theNτ‐methylation of histamine and structurally related compounds. Measurement of HNMT activity in the RBC makes it possible to access variation in the enzyme activity that may reflect differences in less accessible tissues such as brain. Previously reported high family correlations for RBC HNMT activity suggested that genetic inheritance plays a major role in the regulation of variation in this enzyme. In the present study we completed complex segregation analyses of RBC HNMT activity of 241 individuals in 51 nuclear families that were randomly ascertained through children in the Rochester, Minnesota public school system in order to characterize the mode of inheritance of this important enzyme. We found evidence for major gene influence on the regulation of RBC HNMT activity. Both transformed and untransformed data support the presence of Mendelian major gene segregation, but the gene frequency differences do not indicate a direct correspondence between genotypes inferred from the two sets of analyses. Analyses of the skewed untransformed data indicated the presence of a relatively rare (Q= 0.121) additive major gene for high activity, with the three overlapping genotype distributions representing 77, 21, and 2 % of individuals. Analyses of the normalized transformed data indicated the presence of a common (Q= 0.71) additive major gene for high activity, with the three overlapping genotype distributions accounting for 9, 41, and 50 % of individuals. The analyses of transformed data give the best fit as well as the most parsimonious Mendelian major gene model. However, we cannot rule out the possibility of multiple alleles, and analyses of untransformed data provide some support for a third allele. Molecular studies will be needed to validate and characterize the alleles that regulate RBC HNMT activity levels in humans. © 1993 Wiley‐Liss. Inc.
Assessment of adiposity in an Indian population: Familial correlations
Authors: Nirmala A. , Mitchell L. E. , Rice T. , Chengal Reddy P. , Rao D. C.
Published: June 2005

Familial correlations for five measures of adiposity were assessed using data from 473 nuclear families residing in the Chittoor district of Andhra Pradesh, India. Fat patterning, measured as the ratio of trunk to extremity subcutaneous fat, and the ratio of the subscapular to the sum of the subscapular and suprailiac skinfolds, and three measures of generalized fatness: body mass index, the sum of six skinfolds and the sum of three trunk skinfolds were analyzed. Maximum likelihood estimates of the familial correlations were obtained for each phenotype, after adjusting for the effects of (1) age within sex, and (2) current levels of energy intake and expenditure, and age within sex. Hypotheses regarding sex‐specific, and generational differences in these correlations were assessed for each phenotype, under both adjustment schemes. The strength and pattern of the familial correlations for the three measures of generalized fatness were markedly influenced by the specific adjustments applied to the data. In contrast, the familial correlations for the fat patterning phenotypes were quite similar under the two adjustment schemes. Comparison of our results with previously published data indicates that the familial correlations for a subset of these adiposity measures may be heterogeneous across populations. © 1993 Wiley‐Liss. Inc.
Chromosome‐based method for rapid computer simulation in human genetic linkage analysis
Authors: Terwilliger Joseph D. , Speer Marcy , Ott Jurg
Published: June 2005

Computer‐based simulation has been an important method in human linkage analysis for a long time. Typically, such analyses have been performed by simulating a set of linked markers according to the intermarker recombination fractions, under the assumption of no genetic interference. A novel approach is proposed in which such simulations can be performed using chromosome‐based methods, rather than traditional recombination fraction‐based methods. We propose simulating pedigree data using a crossover formation (CF) process to generate the number of crossovers and their locations in Morgans along the entire length of a chromosome. By this method, one can generate simulated multilocus data for any number of loci on a chromosome much more efficiently than with the currently available methods like those used in the SLINK or SIMLINK programs. Further, interference can be incorporated directly in this method, which is not possible with existing packages. © 1993 Wiley‐Liss, inc.
Improved sib‐pair linkage test for disease susceptibility loci
Authors: Faraway Julian J.
Published: June 2005

An improved sib‐pair test for linkage is introduced which is superior to the previously proposed tests. The test is derived from the standard chi‐squared goodness of fit statistic by restricting the alternative hypothesis to the genetically possible. Critical values are given and exact power comparisons are made with the previously proposed tests. The new test is shown to be more powerful for finite samples as well as being asymptotically uniformly most powerful. © 1993 Wiley‐Liss, Inc.
Reporting bilaterality status in first‐degree relatives with breast Cancer: A validity study
Authors: Breuer Brenda , Kash Kathryn M. , Rosenthal Gladys , Diemer Karen , Osborne Michael P. , Miller Daniel G.
Published: June 2005

The objective of this study was to validate reports on the bilaterality status of breast cancer in first‐degree relatives of women with a strong family history of the disease; i.e., women with 1) two first‐degree relatives who have, or have had, breast cancer; 2) one first‐ and one second‐degree affected relative; or 3) one first‐degree relative with diagnosis of breast cancer before the age of 50 years and/or bilateral breast cancer. We were able to obtain hospital records for 94 affected relatives of 83 patients who agreed to participate in the study. The accounts of these women were compared to the bilaterality status indicated in the hospital records of the affected relatives. Inconsistencies that might have been attributed to incomplete medical records were resolved through personal interviews with the participants, and when indicated, with other family members or the physician of the affected relative. Overall, 89.4% (84/94) of the reports validated in this manner were correct. Participants who reported unilateral breast cancer in a first‐degree relative were correct 94.4% (68/72) of the time. Similarly, 94.0% (47/50) of the accounts concerning affected living relatives were accurate, regardless of whether the participant had indicated unilateral or bilateral disease. However, participants who reported bilateral breast cancer in a deceased relative were accurate only 61.5% (8/13) of the time. Incorrect reports were associated with misunderstanding of medical terminology, especially if the participant was young at the time of the diagnosis of her relative. © 1993 Wiley‐Liss, Inc.
Homozygous parent affected sib pair method for detecting disease predisposing variants: Application to insulin dependent diabetes mellitus
Authors: Robinson Wendy P. , Barbosa Jose , Rich Steven S. , Thomson Glenys
Published: June 2005

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant (s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P< 0.05 andP< 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non‐Asp at DQP position 57 and Arg at DQa position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition. © 1993 Wiley‐Liss, Inc.
Epistatic modeling in rheumatoid arthritis: An application of the Risch theory
Authors: Rigby Alan S. , Voelm Lianne , Silman Alan J.
Published: June 2005

Rheumatoid arthritis (RA) is a disease of unknown etiology but with a presumed complex pattern of inheritance. Risch [Am J Hum Genet 46:222–228, 1990] has shown that the recurrence risk ratio, λR, (which is defined as the risk to type R relatives vs. the population prevalence) can be used to evaluate patterns of inheritance in genetically complex diseases. We have used the Risch theory to examine some multiple locus models of inheritance in RA. Recurrence risk ratios in MZ twins and in 1st, 2nd, and 3rd degree relatives are summarized from the literature. The limited data available supports at least a two‐locus model of inheritance for RA (assuming that one locus is HLA). Better estimates of the recurrence risk ratios in RA families are required so that the Risch theory can be pursued further. © 1993 Wiley‐Liss, Inc.
Scope and strategies of Genetic Epidemiology: Analysis of articles published inGenetic Epidemiology, 1984–1991
Authors: Khoury Muin J. , Beaty Terri H. , Cohen Bernice H.
Published: June 2005

Genetic epidemiology is a relatively new discipline that seeks to unravel the role of genetic factors and their interactions with environmental factors in the etiology of diseases, using population and family study approaches. To characterize the overall direction and emphasis of research strategies used in this field, we reviewed original research articles published in the journal Genetic Epidemiology since its inception in 1984 until the end of 1991. Of 259 published original articles, 92 (35%) focused primarily on methodologic/statistical developments, most commonly in the area of linkage analysis/gene mapping, and 167 (65%) articles were applied or data‐derived. Only 42 articles (16%) were population studies, and 217 (84%) were family studies. Most family studies dealt with genetic analysis of pedigree data using segregation and linkage analyses. Of the 137 applied family studies, 73 (53%) were drawn from well‐defined populations, and only 40 (29%) considered specific environmental factors in their analyses. These findings clearly indicate a rapid growth in the methodologic and statistical aspects of genetic epidemiology, and in the emphasis on family‐based studies and genetic analysis methods. Further developments in genetic epidemiology will require greater integration of epidemiologic approaches of study design and analyses into population and family studies of disease etiology. © 1993 Wiley‐Liss, Inc.
Genetic analysis of Alzheimer's disease: A summary of contributions to GAW8
Authors: Wijsman Ellen M.
Published: June 2005

Participants in the Alzheimer's disease component of GAW8 had access to three collections of pedigrees, complete with marker data from chromosomes 19 and 21. There were a total of 94 independent pedigrees and more than 2,000 individuals. Onset of the disorder varied widely among pedigrees. These data are briefly summarized along with a discussion of the problems associated with performing genetic analyses of Alzheimer's disease. The majority of the workshop participants performed an analysis either with some of the data contributed to the workshop or with data simulated on pedigrees of the same structure and disease status as were contributed. There were also a few purely methodological contributions. The contributions are summarized in three general areas: family association and phenotype, linkage analysis, and heterogeneity tests. © 1993 Wiley‐Liss, Inc.
Linkage analysis in familial Alzheimer disease: Description of the Duke and Boston data sets
Authors: Pericak‐Vance M. A. , St. George‐Hyslop P. H. , Gaskell P. C. , Growdon J. , Crain B. J. , Hulette C. , Gusella J. F. , Yamaoka L. , Tanzi R. E. , Roses A. D. , Haines J. L.
Published: June 2005

Familial Alzheimer disease is a neurological disorder of adult onset. Three research centers have each contributed their families and genetic linkage data for combined analyses. The data from the Duke and Boston centers, comprising 73 pedigrees for whom numerous markers on chromosomes 19 and 21 were typed, are described. © 1993 Wiley‐Liss, Inc.
Linkage analysis of Alzheimer's disease with methods using relative pairs
Authors: Blossey Heike , Commenges Daniel , Olson Jane M.
Published: June 2005

Four relative‐pair methods for detecting genetic linkage were applied to familial Alzheimer's disease data. Results obtained using an extended Haseman‐Elston test and a weighted rank pairwise correlation test, which both use information from all relative pairs, were consistent with previously published likelihood results and appear to be more powerful than affected sib pair methods. © 1993 Wiley‐Liss, Inc.
Detecting heterogeneity with the affected‐pedigree‐member (APM) method
Authors: Matise Tara Cox , Weeks Daniel E.
Published: June 2005

We have developed a novel test of heterogeneity based on the APM method. We present tests of this method on both empiric and simulated data. © 1993 Wiley‐Liss, Inc.
The effect of misspecifying allele frequencies in incompletely typed families
Authors: Knapp Michael , Seuchter Susanne A. , Baur Max P.
Published: June 2005

To examine the effect of a misspecified marker allele frequency, the segregation of a marker unlinked to Alzheimer's disease was simulated for the typed members of the GAW8‐FAD4 pedigree. Lod scores were calculated for different assumed marker allele frequencies. The results show that a misspecification of marker frequency can lead to spuriously high lod scores. The affecteds‐only method for linkage analysis is even more sensitive in regard to marker frequency misspecification. Therefore, we recommend estimation of marker allele frequencies from the actual family data. The simple estimator we considered in this paper seems to be sufficient. © 1993 Wiley‐Liss, Inc.
Linkage analysis of a complex disease: Application to familial Alzheimer's disease
Authors: Neuman R. J. , Rice J. P. , Hampe C. L. , Burroughs T. E. , Moldin S. O.
Published: June 2005

Evidence for linkage of the Alzheimer's gene to markers on chromosomes 19 and 21 was assessed using single‐locus and two‐locus models of inheritance. Families were divided into groups determined by their average age at onset. The youngest group produced higher lod scores for markers on chromosome 21 while an older group showed evidence for linkage to markers on chromosome 19. Two‐locus models of disease were used to analyze the youngest group for linkage to pairs of markers on chromosome 21 and an older group with markers on chromosome 19. © 1993 Wiley‐Liss, Inc.
A two‐locus model for familial Alzheimer's disease?
Authors: Macciardi Fabio , Cavallini M. Cristina
Published: June 2005

The present findings for familial Alzheimer's disease suggest a possible linkage to gene(s) on chromosome 21 for the early onset form and to chromosome 19 for the late onset. Since these results are not unequivocal, possible alternative hypotheses include the effect of genetic heterogeneity or of an oligogenic model of segregation for FAD. © 1993 Wiley‐Liss, Inc.
Heterogeneity testing for Alzheimer's disease within and between data sets
Authors: Miller L. L. , Ploughman L. M. , Marazita M. L.
Published: June 2005

We examined the three Alzheimer's disease (AD) family data sets for heterogeneity. Four markers that were represented in all three data sets were selected for analysis. Markers BCL3EcoR‐Mlu and D19S13/TaqI were chosen for chromosome 19 and D21S13/TaqI and D21S16/XbaI for chromosome 21. Homogeneity testing was performed on the data by use of Morton's pre‐divided samples test (PS‐test) and Smith's admixture test (A‐test). The C‐test of MacLean et al. [1992] was also used to test for linkage in the presence of heterogeneity. Assuming homogeneity, there was significant evidence of linkage to AD for BCL3, D19S13, D21S16 in the Duke data set and D19S13, D21S16 in the Boston data set. C‐tests also provided evidence of linkage for BCL3 and D21S13 in the Duke data set, and D21S16 in the Boston data set. No evidence for heterogeneity within the data sets was found for any of the four markers using either the A‐test or the C‐test. For marker BCL3, PS‐tests found evidence of heterogeneity between the three data sets and between early‐ versus late‐onset families combined over all data sets. © 1993 Wiley‐Liss, Inc.
Two new approaches toward linkage heterogeneity of FAD: Two‐locus models and age of onset as a discriminator
Authors: Mérette Chantal , Lehner Thomas , Ott Jurg
Published: June 2005

We present two new approaches to the problem of genetic heterogeneity encountered in linkage analysis of familial Alzheimer's disease. We used two‐locus models to represent the possible existence of two disease genes while allowing for intrafamilial heterogeneity, and modeled the occurrence of the early onset form of the disease with epistasis. We developed a mixture model of heterogeneity where the early and late onset family types can be either linked to chromosome 19, 21, or unlinked, and where it is not necessary to arbitrarily preclassify a family into an early or late onset family type. © 1993 Wiley‐Liss, Inc.
Lack of evidence for maternal effect in familial Alzheimer's disease
Authors: Payami Haydeh , Hoffbuhr Kristen
Published: June 2005

Mitochondrial defects may be involved in Alzheimer's disease (AD) by lowering the oxidative phosphorylation efficiency at an earlier age. To investigate the possible contribution of an inherited mitochondrial DNA defect to familial AD (FAD), we examined the Genetic Analysis Workshop (GAW) data for evidence of maternal transmission and the effect on the age of onset. We found no evidence in support of inherited mitochondrial defects in the GAW FAD kindreds. © 1993 Wiley‐Liss, Inc.
A bootstrap approach to estimating power for linkage heterogeneity
Authors: Leal Suzanne M. , Ott Jurg
Published: June 2005

We examined the power of detecting linkage heterogeneity when the null hypothesis is that all families are linked to one locus (A) and the two alternative hypotheses are either (1) a proportion of the families are linked to locus A and the remaining families are linked to a second locus B or (2) a proportion of the families are linked to locus A or B and a third proportion of the families are unlinked to either locus. The power of detecting linkage heterogeneity is estimated for various proportions of families linked to loci A, B or unlinked to either locus (sampling under the alternative hypothesis). To estimate the significance level, the data set is sampled under the null hypothesis. For sampling under both hypotheses, a bootstrap approach is employed, sampling the simulated pedigrees with replacement.

The power to detect linkage heterogeneity is strongest when the recombination fraction is 0 and equal proportions of the families are linked to loci A and B. The power decreases as the recombination fraction increases, the propor‐tion of unlinked families increases and the disparity between the proportion of the families linked to either locus A or B increases. In the data set of 32 Duke Familial Alzheimer Disease families, when equal proportions of families are linked to loci A and B, the power to detect linkage heterogeneity is 0.94 using a likelihood ratio criterion of 10:1. The p value that corresponds to the likelihood ratio of 1O:l is estimated as 0.013 with a 95% confidence interval for p ranging from 0.012 to 0.014. © 1993 Wiley‐Liss, Inc.
A novel polylocus method for linkage analysis using the lod‐score or affected sib‐pair method
Authors: Terwilliger Joseph D. , Ott Jurg
Published: June 2005

A novel approach to combining data from multiple linked loci is proposed that can provide substantial increases in power over normal two‐point linkage analysis or sib‐pair analysis, with a substantial saving in computing time over traditional multipoint methods. © 1993 Wiley‐Liss, Inc.
Genetic heterogeneity in Alzheimer's disease: A grade of membership analysis
Authors: Corder Elizabeth H. , Woodbury Max A.
Published: June 2005

Grade of membership analysis (GoM) may have particular relevance for genetic epidemiology. The method can flexibly relate genetic markers, clinical features, and environmental exposures to possible subtypes of disease termed pure types even when population allele frequencies and penetrance functions are not known. Hence, GoM may complement existing strategies that sometimes fail in the presence of heterogeneity or when case definition is not well established. To illustrate the method, individuals in the Seattle data set were evaluated with respect to affection status, age at onset, pedigree, sex, and genetic markers on chromosomes 19 and 21. Seven pure types were found which we have designated as: Early Onset, Late Onset, Probable, and Unaffected 1 to Unaffected 4. © 1993 Wiley‐Liss, Inc.
The Kaiser‐Permanente women twins study data set
Authors: Austin Melissa A.
Published: June 2005

The Kaiser‐Permanente Women Twins Study began with the establishment of a large registry of twins at Kaiser‐Permanente, a managed health care program in Oakland, California. In 1978–79, 434 pairs of women twins, 255 monozygotic and 179 dizygotic, with average age 41 years, were recruited from this registry for a study of coronary heart disease risk factors. Previous analyses of these data have shown moderate heritability for blood pressure and high heritability for lipids, even after adjustment for differential environmental covariance between twin types. For GAW8, the data provided included age, race, weight, height, blood pressure, lipids, smoking, alcohol consumption, exercise, degree of contact between co‐twins, menstrual status, and medication for hypertension. Exam 2 of this cohort was completed in 1989–90 and has recently reported nearly complete heritability for lipoprotein(a). © 1993 Wiley‐Liss, Inc.
Lipoprotein subclasses in genetic studies: The Berkeley data set
Authors: Krauss Ronald M. , Williams Paul T. , Blanche Patricia J. , Cavanaugh Adelle , Holl Laura G. , Austin Melissa A.
Published: June 2005

In conjunction with a study examining the inheritance of LDL subclass patterns in a healthy population, measurements of lipids, lipoproteins, and lipoprotein subclasses were performed in 301 individuals in 27 kindreds. Questionnaires were used to obtain information on use of medications, hormones, cigarettes, and alcohol. Laboratory data from this study (the Berkeley data set) include measurements of LDL and HDL size subclasses by nondenaturing gradient gel electrophoresis, and measurement of apolipoprotein A‐I by radial immunodiffusion. © 1993 Wiley‐Liss, Inc.
The HGAR1 familial hypercholesterolemia pedigree
Authors: Bailey‐Wilson Joan E. , Elston Robert C.
Published: June 2005

Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley‐Liss, Inc.
A genetic and environmental time series analysis of blood pressure in male twins
Authors: Colletto Gloria M. D. D. , Cardon Lon R. , Fulker David W.
Published: June 2005

Systolic and diastolic blood pressures were measured on 254 monozygotic (MZ) and 260 dizygotic (DZ) male twin pairs, during middle age (average age 48 years) and at two later age points. Genetic and environmental components of covariation were modeled by time series. For both measures, shared environmental influences were absent and specific environmental influences were largely time‐specific. Although heritability was about 0.5 at each time point, genetic variation present at middle age contributed only about 60% to that present 9 years later, the remaining 40% being new. Fifteen years later, at the third time point, no new genetic variation was evident, variation in individual differences being entirely attributable to genetic differences laid down at the two earlier ages. © 1993 Wiley‐Liss, Inc.
Correlation analysis of twin data with repeated measures based on generalized estimating equations
Authors: Grove John S. , Zhao Lue Ping , Quiaoit Filemon
Published: June 2005

Repeated measures allow additional tests of common assumptions in twin correlation analysis. Analysis of log serum triglyceride level in NHLBI male twins using generalized estimating equations disclosed that the mean and variance shifted across exams, presumably because of changes in laboratory practice. © 1993 Wiley‐Liss, Inc.
LISREL modeling of high density lipoprotein cholesterol (HDL) levels in male twins
Authors: Schwartz Joseph E. , Yuan Huixing , Mendell Nancy R. , Finch Stephen J.
Published: June 2005

Based on the LISREL modeling approach for data from monozygotic (MZ) and dizygotic (DZ) twins [Heath et al., 1989; Neale and Cardon, 1992], the hypothesized variance of the logarithm of high density lipoprotein cholesterol due to additive genetic factors was estimated to equal 19% for males. Unobserved common environment accounted for 32% of the variance of log HDL. Both estimates controlled for body mass, alcohol consumption, and smoking. The model had very strong goodness‐of‐fit indices. © 1993 Wiley‐Liss, Inc.
Use of generalized estimating equations in segregation analysis of continuous outcomes
Authors: Stram Daniel O. , Lee Hang , Thomas Duncan C.
Published: June 2005

The use of generalized estimating equations (GEE) [Liang and Zeger, 1986] is explored as a potential alternative to maximum likelihood methods for segregation analysis of continuous phenotypes. We discuss the number of sample moments required by GEE to estimate parameters in simple major gene models, and the computational burden of the GEE methods applied to large pedigrees. © 1993 Wiley‐Liss, Inc.
Complex segregation analysis of LDL peak particle diameter
Authors: Austin M. A. , Jarvik G. Pairitz , Hokanson J. E. , Edwards K.
Published: June 2005

A predominance of small low‐density lipoprotein (LDL) particles, as determined by gradient gel electrophoresis (GGE), has been proposed to be a common genetic marker for risk of coronary heart disease. Previous analyses of the families in the Berkeley data set defined a dichotomous trait based on the LDL size distribution by GGE: subjects with a predominance of small LDL particles have LDL subclass “pattern B,” while those with a predominance of large LDL particles have LDL subclass “pattern A.” Using this definition, previous complex segregation analyses demonstrated a single major gene effect on pattern B with a dominant or additive mode of inheritance, and reduced penetrance in young males and premenopausal women. In the present analyses, a continuous variable denoted LDL peak particle diameter is used, reflecting the size (diameter in Å) ofthe major LDL subclass, for comparison with the dichotomous LDL subclass pattern classification. After adjusting for age and gender, the results demonstrate a single major Mendelian gene effect, but the exact mode of inheritance could not be established. Thus, analysis of the continuous variable was not superior to that of the dichotomous classification in determining the mode of inheritance of the proposed single gene controlling LDL subclasses. © 1993 Wiley‐Liss, Inc.
A bivariate genetic analysis of HDL‐ and LDL‐cholesterol incorporating measured covariates: A gibbs sampling application
Authors: Mack Wendy J. , Gauderman W. James , Thomas Duncan C.
Published: June 2005

We analyzed HDL‐ and LDL‐cholesterol levels as a bivariate phenotype in 27 families as a function of major genes, polygenes, and measured covariates using a Monte Carlo sampling technique called Gibbs sampling. Major genes and polygenes exhibited strong effects, when considered separately. While a major gene versus polygene model could not be clearly differentiated for HDL‐C, polygenes appeared to play a stronger role than a major gene for LDL‐C. There was no evidence of linkage between the two major genes for HDL‐ and LDL‐C, and the correlation in polygenes was negative. The analyses illustrate the potential applicability of Gibbs sampling to such complex problems as the multivariate analysis of continuous phenotypes. © 1993 Wiley‐Liss, Inc.
Compound regressive models for quantitative multivariate phenotypes: Application to lipid and lipoprotein data
Authors: Bagchi P. , Jiang O. , Bonney G. E.
Published: June 2005

In this paper we consider the compound version of the class D regressive models for a p variate phenotypic outcome. The likelihood function is noted and the results are illustrated with the Donner Laboratory data, without the assumption of a major gene for the brevity of presentation. © 1993 Wiley‐Liss, Inc.
Linkage analysis in a large pedigree ascertained due to essential familial hypercholesterolemia
Authors: Bailey‐Wilson Joan E. , Wilson Alexander F. , Bamba Vaneeta
Published: June 2005

Sib‐pair linkage analysis was used to screen a large pedigree, ascertained through four members with hypercholesterolemia, for evidence of linkage between 12 quantitative traits and 15 genetic marker loci. Traits were analyzed on the untransformed, natural log and square root‐transformed scales. After adjusting for multiple tests, there is a suggestion of linkage between height and the Kidd blood group on chromosome 18 and between VLDL cholesterol, and possibly triglyceride, and KM on chromosome 2. © 1993 Wiley‐Liss, Inc.
Genetic control of macromolecular synthesis during development of an ascidian: Ascidia nigra
Authors: Smith Kirby D.
Published: June 2005

During early tunicate development, there are two periods of rapid protein synthesis. The first begins shortly after fertilization and continues until about the four cell stage, the second begins at gastrulation. Only the second increase in the rate of protein synthesis is inhibited by actinomycin‐D. In addition to the initial high rate of synthesis there is some protein synthesis throughout early development which is insensitive to treatment with actinomycin‐D. The tunicate embryo thus shows two kinds of genomic control during development. It is suggested that one of them operates at the level of the synthesis of new messenger RNA, and the other at the level of translation of already existing, stable, messenger RNA. This dichotomy of regulatory mechanisms is similar to that occurring during sea urchin development.

It is also shown that RNA synthesis first begins around the four cell stage in the Ascidian embryo and that this synthesis is sensitive to treatment with actinomycin‐D. It is postulated that this early synthesis of RNA accounts for the difference between mosaic and regulative development.
Polar body and pronucleus formation in the pig egg
Authors: Baker R. D. , Dziuk P. J. , Norton H. W.
Published: June 2005

Pig eggs were recovered at known time intervals after insemination and ovulation. The number of sperm attached to the zona pellucida and the proportion of eggs fertilized increased continuously from two hours to 48 hours after insemination. Some eggs had cumulus cells until as late as 12 hours after ovulation. Sperm penetrated the eggs between six and 12 hours after ovulation and pronuclei persisted between eight and 12 hours after ovulation. The second meiotic division appeared to take place in a bulge from the cytoplasm. The second polar body was formed in this bulge and the female chromatin then migrated back into the cytoplasm.
Secretion from normal and supersensitive avian salt glands
Authors: Gill James B. , Burford Hugh J.
Published: June 2005

The sensitivity of the chronically denervated salt gland of the domestic goose to hypertonic, oral salt loading was investigated. In conscious geese the chronically denervated salt gland was supersensitive to an oral salt load. d‐Aldosterone did not appear to stimulate either the normal or denervated glands above control experiments. However, aldosterone did have a tendency to cause prolongation of secretion time.
Polymorphism of albumin‐like proteins in the South American tetraploid frog Odontophrynus americanus (Salientia: Ceratophrydidae)
Authors: Beçak Willy , Schwantes Arno R. , Schwantes Maria Luiza B.
Published: June 2005

Utilizing starch gel electrophoresis, a study was made on the albuminlike plasma protein of a tetraploid South American species of frog. No allelic polymorphism at this locus was indicated in the congeneric diploid species O. cultripes, but five distinct electrophoretic phenotypes were encountered among 141 frogs of the tetraploid species O. americanus. These included two homozygous types each with a single distinctive albumin‐like band, and three heterozygous types. The three heterozygotes differed from each other by relative staining intensity of the bands, and presumably represent 3:1, 2:2, and 1:3 ratios of allelic dosage. The frequency distribution of the five phenotypes among 141 frogs fitted well with the expected values calculated on the basis of the binomial (p + q)4 with allelic frequencies of 0.415 and 0.585.
A study of properties of renal microbodies of the rat,
Authors: Beard Margaret E. , Allen John M.
Published: June 2005

The in vitro response of renal microbodies and lysosomes to a variety of altered physical and chemical conditions was examined. The influence of these conditions upon the integrity of the organelles was determined as that proportion of the total activity of various “marker” enzymes (α‐hydroxy acid oxidase, catalase and D‐amino acid oxidase for microbodies, and acid phosphatase for lysosomes) which was released from the organelles and recovered in the soluble phase following treatment.

Microbodies and lysosomes were separated by differential centrifugation from 15% homogenates of male, rat kidney prepared in 0.25 M sucrose. After exposure to experimental treatments, the preparation was further separated into sediment and supernatant fractions by centrifugation at 100,000 × g for 30 minutes. The sediment and supernatant fractions were assayed to determine the distribution of the “marker” enzymes.

Eighty to 100% of the activities of α‐hydroxy acid oxidase and catalase were found in the supernatant after exposure of the microbody‐lysosome fraction to low concentrations of Triton‐X 100 or digitonin, or after treatment by sonic vibrations or high speed laminar shearing. Lesser but significant proportions of the total activities of these enzymes were recovered in the soluble phase after exposure of the organelles to distilled water, 0.1 M Sorensen's phosphate buffer or 0.1 M TRIS‐HCl buffer prepared in distilled water. Acid phosphatase showed lower levels of release into the supernatant under most of these conditions.

When microbody‐lysosome preparations were exposed to sucrose in concentrations of 0.1 M to 0.8 M to phosphate buffer in 0.25 M sucrose or to TRIS‐HCl buffer prepared in 0.25 M sucrose, the release of α‐hydroxy acid oxidase, catalase and acid phosphatase was insignificant. However, under these conditions D‐amino acid oxidase was released into the soluble phase to a significant extent.

These results suggest that α‐hydroxy acid oxidase and catalase are soluble constituents of renal microbodies while D‐amino acid oxidase is associated firmly with a sedimentable component of the organelle, and that renal microbodies are more fragile than renal lysosomes.
Attempted fertilization of hamster eggs following transplantation into the uterus
Authors: Hunter R. H. F.
Published: June 2005

The possibility of obtaining fertilization of mammalian eggs at sites in the reproductive tract other than the ampulla of the Fallopian tube appears to have received little attention. Following transplantation of recently‐ovulated hamster eggs from the tubes of 66 donors into the uterine horns of a similar number of mated or inseminated recipients at known stages of the estrous cycle, none of 392 recovered eggs was found to be fertilized after periods of between two and eight hours in the uterus. All eggs were completely denuded of cells of the cumulus oophorus and corona radiata at recovery, but spermatozoa were not found attached to or within the zona pellucida. Large globules, presumably derived from deutoplasmic components of the vitellus, were observed in the perivitelline space of transferred eggs recovered from the uterus on the morning after ovulation; the vitelline membrane appeared to be damaged in a proportion of these eggs. However, apart from such adverse effects of the uterine fluids upon the egg membranes, it should also be considered that hamster spermatozoa may require exposure to the environment of the Fallopian tube before they acquire the ability to penetrate the eggs.
Crystalloid formation in unfertilized mouse ova under influence of cytochalasin B
Authors: Moskalewski Stanislaw , Sawicki Wojciech , Gabara Barbara , Koprowski Hilary
Published: June 2005

Ova from superovulated Swiss albino ICR mice were exposed to 1, 10, and 40 μg cytochalasin B/ml in Whitten and Biggers medium (WBM) for intervals up to 24 hours. Controls were incubated in ordinary medium or in medium containing dimethylsulfoxide (DMSO) in an amount equivalent to that used to dissolve cytochalasin B, taking dilution into account. The ova were mounted on slides in egg albumin, stained by the Feulgen method and counterstained with light green SF, or they were processed for electron microscopy. The DMSO treatment, as determined by either light or electron microscopy, had no essential effect. Eggs treated with 10 or 40 μg cytochalasin/ml did not exhibit the fragmentation observed in some of the control ova. Treated eggs contained either several spherical bodies, which sometimes reached a size of 8 to 10 μ, or as many as 20 smaller bodies, stainable with light green SF and positive for proteins when stained with mercury‐bromphenol blue. These bodies, first observed after exposure for eight hours to cytochalasin, were revealed by electron microscopy to be groups of crystalloids which occasionally entrapped microfilaments or granules. Neither the spacial relationship of crystalloids to cell organelles nor the preliminary stages of their formation could be observed. Since little protein synthesis occurs in unfertilized eggs, and the addition of 50 and 250 μg of puromycin did not prevent formation of these bodies, it is suggested that they were formed by the crystallization of proteinaceous material already present in the eggs.
Gene transcription in mosaic embryos. II. Polyribosomes and messenger RNA in early development of the coot clam, Mulinia lateralis
Authors: Kidder Gerald M.
Published: June 2005

Embryos of the coot clam, Mulinia lateralis, have been found to synthesize the several types of RNA in essentially the same temporal pattern as observed in the regulative embryos of a variety of deuterostome organisms. Since it remained to be shown whether the RNA produced in early development of mosaic embryos such as those of the clam has the same function as that synthesized by regulative embryos, a study of the entry of newly‐synthesized RNA into polyribosomes of Mulinia embryos was carried out.

Unfertilized oocytes contain a detectable number of polyribosomes, and within 45 minutes after fertilization this number has increased. The proportion of ribosomes engaged in polyribosomes continues to increase throughout development, in the absence of any change in the overall size distribution of the polyribosomes. Newly‐synthesized RNA can be found in specific association with light polyribosomes as early as the two‐cell stage, and the polyribosome classes receiving this RNA are active in protein synthesis. The RNA entering polyribosomes in late cleavage was purified and analyzed by sucrose gradient centrifugation and found to consist predominately of the 8–10s species which had been observed previously in Mulinia embryos from early cleavage through gastrulation. The similarities between this RNA and the 9–10s RNA discovered in sea urchin embryos, which is considered to include the mRNA's for chromosomal histones, suggest that early RNA synthesis in clam and sea urchin embryos fulfills basically the same function. This finding discourages speculation concerning possible differences in gene transcription patterns between early mosaic and regulative embryos.
Electrical interaction among large cells in the cardiac ganglion of the lobster, Panulirus japonicus
Authors: Tazaki Kenro
Published: June 2005

To investigate electrical interaction among large cells in the lobster cardiac ganglion, electrotonic transmission between the somata of two such cells was observed by applying current pulses of two different durations and recording induced responses in the membrane potential of soma. The brief potential changes induced in one soma were transmitted to an adjacent soma through electrotonic pathways in the same way as the longer potential changes. However attenuation was greater for the shorter pulses. The amplitude of the soma spike markedly decreased compared to that of the axon spike, and the ratio was about 5.5. The soma spike was not a regenerative response of the soma membrane, but it was an electrotonic spread of the axon spike. The attenuation ratio of the soma spike was almost the same as that measured for a brief potential change such as a spike applied to the soma. These findings indicate that the soma spike spreads electrotonically to the adjacent soma through the electrical connections, while the axon spike does not. Such electrical transmission of the spike was extremely weak. The slow potential, electronic transmission of which had been observed between large cells, was restricted to the soma. The results suggest that the electrotonic pathways interconnect the somata of large cells in the anterior part of the ganglionic trunk, but not the axons. Electrical transmission of the spike through the pathways is very weak because of the inexcitable membrane of the somata. The electrotonic pathways are considered to be fibre‐like connections between dendrites arising from the somata.
Glycogen in lens of tunicate tadpole (Chordata: Ascidiacea)
Authors: Eakin Richard M. , Kuda Aileen
Published: June 2005

The larval eye (cerebral ocellus) of an ascidian, Ciona intestinalis, possesses a lens of three cells: in the center of each is a large granular body. Several lines of evidence indicate that the lens bodies are composed of beta particles of glycogen. The granules have diameters of 300–400 Å; they stain lightly with lead citrate; they are PAS positive (periodic acid Schiff reaction); they are digestible with alpha amylase; and they respond positively to Thiéry's silver proteinate stain.
Kinetic studies on the mating reaction of Tetrahymena pyriformis, Syngen 1
Authors: McCoy J. Wynne
Published: June 2005

Mating is induced in Tetrahymena pyriformis, syngen 1, by mixing starved and washed cultures of unlike mating type. A refractory period of at least 35 minutes is observed before mating begins. The duration of the “waiting period” is shown to depend on concentrations of cells of each mating type, in such a way that the rate of approach of mating is inversely proportional to the product of the concentrations of cells of the two mating types. These observations suggest that the cells “count” collisions with cells of unlike mating type during the waiting period. Exposure of the starved cultures to a low concentration of reactive cells of unlike mating type was used in a “conditioning” experiment. The waiting period is reduced when such conditioned stocks are mixed. The results of this experiment also support the interpretation that the rate of approach of mating depends on the number of collisions experienced by the cells.
Fertilization of the mouse oocyte: Sequence and timing of nuclear progression to the two‐cell stage
Authors: Donahue Roger P.
Published: June 2005

From 88 superovulated, mated CFI (Carworth) females, 2643 eggs were collected at two hourly intervals between 12 and 36 hours after administration of human chorionic gonadotrophin and then fixed, stained and examined as whole‐mounts by light microscopy. Mating and ovulation were essentially complete at 10 and 14 hours respectively.

Metaphase II oocytes continued to decrease in number until 20 hours. Telophase II, a maximum at 16 hours (22% of all oocytes), was not seen after 20 hours. Pronuclei first appeared at 16 hours and at 24 hours, 87% of the ova were pronuclear. Metaphase of first cleavage, first detected at 28 hours, represented 17% of the ova at 32 hours. The first cleavage division occurred between 30 and 34 hours.

The pronuclear chromatin network, which is always visible, is more diffuse in the larger, male pronucleus. During first cleavage prophase, the chromatin strands shorten and distinct chromosomes appear, those of male origin being less condensed. The two chromosome groups then combine to form first cleavage metaphase. Pronuclear fusion was not observed.

Twenty‐three per cent of the ova had not undergone first cleavage by 36 hours: 6% were at earlier stages and presumably arrested while 14% were fragmented or had degenerated metaphase II chromosomes. Anomalies of oocyte maturation and fertilization accounted for 1.6% of all ova.
The effects of the nicotinamide sensitive teratogen 3‐acetylpyridine on chick limb mesodermal cells in culture: Biochemical parameters
Authors: Caplan Arnold I.
Published: June 2005

3‐acetylpyridine (3AP) causes severe muscular hypoplasia in vivo and seems to potentiate chondrogenic expression of limb bud cells in vitro. In both cases nicotinamide completely relieves these effects. In cell cultures, 3AP causes a substantial drop in nicotinamide incorporation. This decreased incorporation represents not only decreased cellular pools of nicotinamide but also decreased DPN‐TPN pools. 3AP also decreases the rate of RNA, protein, and mucopolysaccharide synthesis. 3AP does not affect the rate of DNA synthesis which is constantly decreasing as chondrogenic expression increases. Even though the rates of macromolecular synthesis seem to be reduced, the specific activity of an obligatory enzyme for mucopolysaccharide assembly, UDP glucose pyrophosphorylase, dramatically increases with 3AP‐treatment. This is interpreted to mean that 3AP potentiates of cartilage synthesizing machinery which is observed as a potentiation of chondrogenic expression. These data are discussed with regard to nicotinamide's proposed role in affecting the development of chick limb mesodermal cells into muscle and cartilage producing phenotypes. It is proposed that alterations in local concentrations of essential molecules like nicotinamide, DPN, or TPN can control phenotypic expression.