bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage between the APOB gene and serum apoB levels in a large pedigree from the Bogalusa heart study
Authors: Laing A. E. , Amos C. I. , DeMeester C. , Diep A. , Xia Y. R. , Elston R. C. , Srinivasan S. R. , Berenson G. S. , Lusis A. J. 
Published: June 2005

AbstractMaximum likelihood linkage analyses were performed to test for linkage between serum apoB levels and several candidate gene markers including apolipoprotein B, lipoprotein lipase, hepatic lipase, cholesterol ester transfer protein, and apolipoprotein AI in a large pedigree. Parameters of general Mendelian inheritance derived from maximum likelihood segregation analysis of the serum apoB levels were used in the linkage analysis. The highest two‐point lod score between the quantitative trait and a marker defined by a single restriction digest was 1.86 at recombination fraction (θ) = 0. This was observed for linkage between serum apoB levels and the presence or absence of a PvuII digestion site in the apoB gene. Linkage between serum apoB levels and polymorphisms of the apoB gene defined by the two restriction digests EcoR1 and PvuII was supported by a lod score of 3.30, while inclusion of VNTR typings led to a lod score of 2.33. None of the other candidate genes gave positive evidence of linkage. © 1994 Wiley‐Liss, Inc.This article is a US government work and, as such, is in the public domain in the United States of America.
Sibling correlations and segregation analysis of age‐related maculopathy: The beaver dam eye study
Authors: Heiba Ibrahim M. , Elston Robert C. , Klein Barbara E. K. , Klein Ronald 
Published: June 2005

AbstractSibling correlations were evaluated and segregation analysis was performed on age‐dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the τ'ABfree model, but is rejected under the τ's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age‐related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively. © 1994 Wiley‐Liss, Inc.
The weighted rank pairwise correlation statistic for linkage analysis: Simulation study and application to Alzheimer's disease
Authors: Commenges D. , Olson J. , Wijsman E. 
Published: June 2005

AbstractThe weighted rank pairwise correlation (WRPC) statistic has been proposed as a robust test of genetic linkage, particularly adapted to the analysis of large and complex pedigrees and for age‐dependent and heterogeneous diseases. In this paper a simulation study is presented. Validity and power of the WRPC test are studied and compared to the Haseman‐Elston sibpair method for various types of problems. The power of the WRPC test is slightly lower than the Haseman‐Elston method for analyzing a large number of small randomly chosen pedigrees. It is higher however in presence of genetic heterogeneity or for analyzing large individual pedigrees. Recently, evidence of linkage of Alzheimer's disease with a locus on chromosome 14, D14s43, has been obtained by the Lod‐score method. We reanalyze these data using the WRPC test, essentially confirming the results of the Lod‐score method. The WRPC test statistic is higher than the equivalent Lod‐score statistic for the two pedigrees which show strong evidence of linkage with the two methods. The global WRPC test statistic is slightly lower than the Lod‐score test statistic. The WRPC test, however, makes no hypothesis of a specific genetic transmission model and can be computed very quickly; in addition, an exact P‐value can be computed by simulation for individual pedigrees. © 1994 Wiley‐Liss, Inc.
Lods, wrods, and mods: The interpretation of lod scores calculated under different models
Authors: Hodge Susan E. , Elston Robert C. 
Published: June 2005

AbstractIn this paper we examine the relationships among classical lod scores, “wrod” scores (lod scores calculated under the wrong genetic model), and “mod” scores (lod scores maximized over genetic model parameters). We compare the behavior of these scores when the state of nature is linkage to their behavior when the state of nature is no linkage. We describe sufficient conditions for mod scores to be valid and discuss their use to determine the correct genetic model. We show that lod scores represent a likelihood‐ratio test for independence. We explain the “ascertainment‐assumption‐free” aspect of using mod scores to determine mode of inheritance and we set this aspect into a well‐established statistical framework. Finally, we summarize practical guidelines for the use of mod scores.
The contribution of maternal epilepsy and its treatment to the etiology of oral clefts: A population based case‐control study
Authors: Abrishamchian Ahmad R. , Khoury Muin J. , Calle Eugenia E. 
Published: June 2005

AbstractThe associations between maternal epilepsy and anticonvulsant drug therapy with the risk of oral clefts in the offspring were investigated using data from a population‐based case‐control study. Cases included 238 infants with cleft lip ± cleft palate (CLP) and 107 infants with cleft palate (CP) ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1968 and 1980. Controls included 3029 population‐based normal infants. Histories of maternal epilepsy and drug therapy during pregnancy were compared between cases and controls using maternal interviews and reviews of hospital medical records. Maternal epilepsy was associated with increased risk of nonsyndromic CLP (OR = 3.78, 95% C.I. 1.65–7.88), and less with CP (OR = 1.75, 95% C.I. 0.20–6.99). Therapy during pregnancy was associated with the greatest excess risk (CLP OR = 7.77, C.I. 2.02–26.0; CP OR = 3.61, C.I. 0.08–26.5). The use of polytherapy was associated with the highest risk (CLP OR = 10.5, C.I. 1.52–59.9). Adjustment for potential confounding variables in the study did not change these findings. In this well‐defined population, maternal epilepsy and its treatment account for a small proportion of nonsyndromic oral clefts (attributable fraction CLP = 3.3%, CP = 0.9%). © 1994 Wiley‐Liss, Inc.
Direction of causation: Reply to commentaries
Authors: Neale Michael C. , Duffy David L. , Martin Nicholas G. 
Published: June 2005

AbstractWe reply to the commentaries on the lead papers by Neale et al. [1994a] and Duffy and Martin [1994]. Topics covered include power calculations, cross‐sectional measurement vs. lifetime reports, the appropriateness of the direction of causation (DOC) model, extensions to study causation between the latent variables, sampling of subjects, and heterogeneity. We consider the potential of combining genetically informative research designs with multivariate longitudinal and experimental methods. © 1994 Wiley‐Liss, Inc.
Depression and parental bonding: Cause, consequence, or genetic covariance?
Authors: Neale Michael C. , Walters Ellen , Heath Andrew C. , Kessler Ronald C. , Pérusse Daniel , Eaves Lindon J. , Kendler Kenneth S. 
Published: June 2005

AbstractIt is shown how information on the direction of causation between variables may be obtained from a cross‐sectional study of pairs of relatives. This method is applied to the study of the relationship between ratings of parents' rearing style and depression in their offspring. Adult female twins ascertained from a population‐based registry in Virginia completed the Center for Epidemiological Studies ‐ Depression Scale (CESD) and a 7‐item short form of the Parental Bonding Instrument (PBI) about each of their parents. Two dimensions of parental behavior, overprotectiveness and coldness, were analyzed jointly with depression data in both genetic factor and directional genetic models. Models that specify ratings of parents as a cause of depression in the offspring fit the data significantly better than models that specify depression as a cause of ratings of parents. A still better fit is obtained with models that specify common genetic variance to depression and ratings, though causal models with error variance perform almost as well. In general, ratings of fathers show more genetic and less shared environmental variance than ratings of mothers, which might arise from more consistent treatment of offspring by mothers than by fathers. No effect of children eliciting parental rearing style was detected with these data. The relative merits of instrumental variable, longitudinal, and family approaches to testing causal models are discussed. © 1994 Wiley‐Liss, Inc.
Robust multipoint linkage analysis: An extension of the Haseman‐Elston method
Authors: Olson Jane M. 
Published: June 2005

AbstractThe use of multiple markers, rather than a single marker, can increase the likelihood of detecting linkage to a locus underlying a quantitative trait. In this paper, the Haseman‐Elston sibpair method is extended to include information from multiple markers. The result is a linear regression of the squared pair trait difference on the jointly estimated proportions of genes shared identical by descent at the two closest flanking marker loci. The results strengthen the theoretical motivation for the interval mapping technique proposed by Fulker and Cardon [1994: Am J Hum Genet 54:1092–1103] and extend the method to include information from multiple markers, account for a trait dominance component, and examine the region just outside that defined by the markers. Simulations show that modest increases in power and substantial decreases in bias of parameter estimates are obtained when identity‐by‐descent probabilities are jointly estimated. The regression relationship is also developed for other types of relative pairs. © 1995 Wiley‐Liss, Inc.
Complex segregation analysis of familial diseases with variable age of onset: Comparison of different methods by a simulation study
Authors: Abel Laurent , Garcia André , Demenais Florence 
Published: June 2005

AbstractStandard methods of segregation analysis, such as originally developed in the unified model (UM) or the regressive logistic model (RLM) do not account for age of onset, and use instead age at examination. To take into account age of onset, models should be formulated using survival analysis concepts, as it was recently proposed with a model based on a logistic hazard function (LHM). A simulation study was conducted to compare the performances of the three methods (UM, RLM, and LHM) in analyzing generated familial data with variable age of onset. When the data were simulated under a polygenic hypothesis, all analysis models were robust with respect to the false conclusion of a major gene, if the tests of transmission probabilities were performed properly. When the data were generated under a major gene hypothesis, two main results were observed: (1) the use of the LHM markedly increased the power to detect a major gene, in particular when a genotype by age interaction was introduced in the model; and (2) in the situation of disease‐specific mortality, the use of either UM (whether specific mortality was accounted for or not) or RLM led to both spurious conclusions and bias in parameter estimates. These latter results obtained with the UM and the RLM can be explained by the violation of one constraint of both models observed in a situation of disease‐specific mortality, i.e., given all covariates, the probability of being affected and that of not being affected should sum to 1. The use of methods based on survival analysis concepts is recommended in the study of familial diseases with variable age of onset, especially in the case of a correlation between age of onset and age at examination which is induced by disease‐specific mortality. ©1995 Wiley‐Liss, Inc.
Polymorphism at VNTR Locus 3′ to the apolipoprotein B gene in a tunisian population: Difference from other ethnic groups
Authors: Buresi Catherine , Desmarais Eric , Vigneron Suzanne , Rayana Chiheb Ben , Chaabouni Habiba , Roizes Gérard 
Published: June 2005

AbstractThe Hypervariable Region (HVR) detected at the 3′ end of the apolipoprotein B (Apo B) locus has been the subject of numerous studies. As for many VNTR (variable number of tandem repeat), this locus is highly polymorphic and until now about 20 alleles have been described. The genotype distribution in all populations follows the Hardy‐Weinberg predictions. A bimodal pattern of allele frequency distribution is apparent in all Caucasoid populations. We have analyzed the frequencies of different alleles in a Tunisian population (123 individuals) by the polymerase chain reaction technique and compared our results to those obtained in several ethnic groups. It appears that the distributions of the allele frequencies are very different: for Caucasoid populations, there are two peaks of frequencies for alleles with 36 and 48 repeats, but alleles of intermediate lengths are more frequent. Hixson et al. [(1993) Hum Genet 91:475–479] have shown a similar difference between black and white American populations. We found the same results in a black African group.Some of the repeat units of this HVR contain a Ssp I restriction site and digestion of the PCR products by this enzyme gives different patterns on gradient acrylamide gel [Desmarais et al., 1993, Nucleic Acids Res 21:2179–2184.] The DNA of African individuals (42) has been analyzed to discover the origin of this new allele. Preliminary results indicate that these particular alleles probably arose by introgression from the African population into the Tunisian one. ©1995 Wiley‐Liss, Inc.
Segregation analysis of breast cancer in a population‐based sample of postmenopausal probands: The Iowa women's health study
Authors: Chen Ping‐Ling , Sellers Thomas A. , Rich Stephen S. , Potter John D. , Folsom Aaron R. 
Published: June 2005

AbstractInheritance of a major susceptibility gene for breast cancer has been primarily investigated in families with early‐onset disease. However, familial clustering of late‐onset breast cancer is well documented, and genetic factors may also be relevant. In the Iowa Women's Health Study, we evaluated evidence for a major gene after allowing for measured environmental risk factors. Two hundred sixty‐five incident breast cancer probands were identified from a prospective cohort study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree development form was mailed to the probands to ascertain all first‐degree female relatives. A questionnaire and body measurement protocol were mailed to identified living relatives or surrogates. Segregation analyses were conducted on a total of 1,145 women in 251 families using regressive models as implemented in S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier age‐at‐onset provided the best fit to the data. Incorporation of measured environmental risk factors as covariates yielded no significant improvements in the likelihoods. Approximately 50% of this population could be expected to carry a late‐onset breast cancer susceptibility gene, and 23% of the population is susceptible because of the environment in which they live. Homozygous gene carriers are predicted to have a mean age‐at‐onset of 48 years, over 20 years earlier than heterozygotes; few cases would be expected among non‐gene carriers. In conclusion, the transmission pattern of late‐onset breast cancer may be determined by a common susceptibility gene. ©1995 Wiley‐Liss, Inc.
Genetic analysis of durations: Correlated frailty model applied to survival of Danish twins
Authors: Yashin Anatoli I. , Iachine Ivan A. 
Published: June 2005

AbstractPopulation studies of changes in human morbidity and mortality require models which take into account the influence of genetic and environmental factors on life‐related durations, such as age at onset of the disease or disability, age at death, etc. In this paper we show how a bivariate survival model based on the concept of correlated individual frailty can be used for the genetic analysis of durations. Six genetic models of frailty are considered and applied to Danish twin survival data. The results of statistical analysis allow us to conclude that at least 50% of variability in individual frailty is determined by environmental factors. The approach suggests a method of estimation of the lower bound for the biological limit of human longevity. Directions for further research are discussed. ©1995 Wiley‐Liss, Inc.
Screening a 2 cM genetic map for allelic association: A simulated oligogenic trait
Authors: Duffy David L. 
Published: June 2005

AbstractIn this paper, we explore the use of a variety of familial transmission tests (and case‐control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5‐10 years. We demonstrate a form of the transmission‐disequilibrium test extended to multiallele systems. The methods used were log‐linear and related models implemented largely using standard statistical packages. ©1995 Wiley‐Liss, Inc.
Logistic transmission modeling of simulated data
Authors: Harley John B. , Moser Kathy L. , Neas Barbara R. 
Published: June 2005

AbstractA nonparametric method for linkage analysis has been developed and applied to the Problem 1 data set of the Genetic Analysis Workshop 9. Basically, the univariate matched pair strategy of the transmission disequilibrium test has been adapted to multivariate modeling using the conditional logistic function. After setting the critical value for significance at p ⩽ 0.0001, models at only D5G23 and D1G31 appear to be significant (p < 10−7). Logistic transmission modeling is a powerful method for establishing linkage by disequilibrium. ©1995 Wiley‐Liss, Inc.
Segregation and linkage analysis of the complex trait Q1
Authors: Atwood Larry D. , Mitchell Braxton D. , Stowell Nicole C. 
Published: June 2005

AbstractSegregation and linkage analysis of GAW9 Problem 2 quantitative trait 1 (Q1) was performed. Eight segregation models comprising all possible combinations of the environmental factor (EF), quantitative trait 2 (Q2), and quantitative trait 3 (Q3) as covariates were considered. Seven of the eight segregation models showed strong evidence for a major gene, the other model was marginal. When all genotypes are known, some evidence for linkage (lod > 2) was found to all three of the markers that affect Q1. Furthermore, four of the eight models each showed some linkage (lod > 2) to two of the three markers that affect Q1 with no false positives. Each of these segregation analysis major genes is a hybrid combination of the true multiple loci that affect Q1. © 1995 Wiley‐Liss, Inc.
Relative‐risk regression models using cases and their parents
Authors: Schaid Daniel J. 
Published: June 2005

AbstractRelative‐risk regression models are presented for studies of the association of genetic markers with disease status when the study design uses affected cases and their parents, with or without unaffected sibs. These models generalize the “haplotype relative‐risk” method and allow for censored unaffected sibs; in this sense, these models resemble proportional hazards models that are commonly used in survival analysis. A critical distinction between these models and the usual Cox proportional hazards model is that the frequencies of the genotypes of the cases are compared to controls based on Mendelian expectations, and not simply to the genotypes of the sib controls who are at risk of disease. These models allow modeling of the contribution of specific alleles to the relative risk of disease, as well as interactions of allelic effects with environmental risk factors. To demonstrate the application of these models, we have fit them to the binary affection status of the Problem 2 data set. Four candidate‐gene loci were found to have a significant association with affection status, after allowance for relative risks that decrease with age; two of these associations correctly identified two of the major gene loci, and the other two were false‐positive associations. © 1995 Wiley‐Liss, Inc.
Identification and mapping of mendelian subtypes of disease
Authors: Vieland Veronica J. , Mérette Chantal , Goodman Dan , Rouillard Eric 
Published: June 2005

AbstractWe took as our working hypothesis the premise that there could be a single locus of major effect underlying a subset of cases in the simulated Problem 2 data set, and took as our primary goal the task of mapping that locus. Treating the disease as dichotomous and using discriminant function analysis, we were able to separate affected individuals into two disease categories: Disease Type I (DT‐I) cases, whose disease was by hypothesis caused by the major locus; and Disease Type II (DT‐II) cases, whose disease was by hypothesis produced by other causes. Segregation analysis showed evidence of simple recessive inheritance among the DT‐I individuals. Linkage analysis under the best‐fitting recessive model gave clear evidence of linkage to D1G2. In the generating model, this marker is linked to a major gene for disease with recombination fraction θ = 0, and the mode of inheritance at that locus is recessive (when the trait is considered as a dichotomy). We conclude that when the true model is complex, focussing on subtypes of disease that show evidence of simple Mendelian inheritance may be a useful first step in determining the underlying model and mapping major genes. © 1995 Wiley‐Liss, Inc.
Analysis of breast cancer pedigrees using affected sibship methods
Authors: Barrett Jennifer H. , Rigby Alan S. 
Published: June 2005

AbstractHaplotype‐sharing was examined in sets of affected siblings in the Breast Cancer Linkage Consortium pedigrees [Easton et al., 1993], using both identity‐by‐descent and identity‐by‐state methods. Linkage of the disease susceptibility locus to markers on chromosome 17 was confirmed. Substantial genetic heterogeneity was found, with more young cases being attributable to the putative gene. No differences were found between breast and ovarian cancer, and there was no evidence against a simple dominant mode of inheritance. © 1995 Wiley‐Liss, Inc.
Detection of genome similarity as an exploratory tool for mapping complex traits
Authors: Guo Sun‐Wei 
Published: June 2005

AbstractFor one‐ and two‐trait‐locus models, we show that the lod score based on affected relative pairs or trios is a monotonically increasing function of the genome similarity measured by the proportion of alleles shared identical by descent (IBD) conditional on observed marker data. These results can be generalized to multitrait‐locus models. Thus, we can use conditional probability of genes shared IBD as a tool to reveal chromosomal segments that are likely to harbor the genes underlying the complex traits. © 1995 Wiley‐Liss, Inc.
Changes in gonads and the thyroid gland after hypophysectomy in Ophicephalus punctatus Bloch
Authors: Belsare D. K. 
Published: June 2005

AbstractHypophysectomy in O. punctatus results in the atrophy of gonads and low activity of thyroid gland. The pituitary gland does not exert its influence on immature ova, but has decisive control over mature and maturing ova as well as over the germ cells in the testis. Changes in thyroid follicles in the absence of the pituitary gland are reduction in number, flattened epithelial cells, and accumulation of colloid in the follicles.