bluuebunny/crossref_metadata_2025_split 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

AbstractMethylation 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

AbstractFamilial 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

AbstractComputer‐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

AbstractAn 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

AbstractThe 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

AbstractFor 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

AbstractRheumatoid 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

AbstractGenetic 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

AbstractParticipants 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

AbstractFamilial 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

AbstractFour 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.
The effect of misspecifying allele frequencies in incompletely typed families
Authors: Knapp Michael , Seuchter Susanne A. , Baur Max P. 
Published: June 2005

AbstractTo 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

AbstractEvidence 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

AbstractThe 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

AbstractWe 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

AbstractWe 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

AbstractMitochondrial 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

AbstractWe 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

AbstractA 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

AbstractGrade 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

AbstractThe 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

AbstractIn 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.