bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic factors influencing apolipoprotein AI and AII levels in a kindred with premature coronary heart disease
Authors: Borecki Ingrid B. , Laskarzewski Peter , Rao DC , Williams Roger R. 
Published: June 2005

AbstractA single 51‐member kindred, ascertained on the basis of a normotriglyceridemic proband with depressed high‐density lipoprotein cholesterol (HDL‐C) and myocardial infarctions at ages 40 and 42, was studied with respect to quantitative variation in HDL‐C and apolipoprotein (apo) AI and AII levels. The results of bivariate segregation analysis suggest that the etiology of depressed HDL‐C involves one or possibly two major loci: one has a pleiotropic effect on apo AI and apo AII levels and, possibly another one that affects apo AI levels. Both the major loci were characterized as having a dominant allele leading to depression of the respective trait(s). In addition, analysis of the cosegregation of HDL‐C and apo AI levels gave evidence of residual nonfamilial factors common to both traits, leading to a positive covariance between them. This could reflect the role of apo AI in the transformation of nascent HDL‐C particles into mature ones via its cofactor activity to lecithin cholesterol acyltransferase. The proposed two‐locus model represents one possible etiology for the heterogeneous disorder of hypoal‐phalipoproteinemia. This analysis of a single pedigree does not completely define the genetic mechanism, but it does illustrate a useful new analytic approach.
Significant association of acute lymphoblastic leukemia with HLA‐Cw7
Authors: Müller C.A , Hasmann R. , Grosse‐Wilde H. , Vögeler U. , Bei‐Jun Chen , Dopfer R. , Waller HD , Lalouel J.‐M. 
Published: June 2005

AbstractFrequencies of all defined HLA‐A, ‐B, ‐C (‐DR) antigens were determined in 142 (59) Germans suffering from acute lymphoblastic leukemia (ALL) with differentiation of immunologically defined or age‐related subgroups of the disease. A highly significant rise of the HLA‐C locus antigen Cw7 was found in ALL patients, particularly those over the age of 11 in comparison with local German and Caucasian controls of the Ninth Int. Histocompatibility Workshop (WS). Only slight differences of HLA‐Cw7 frequencies were observed within the four immunologically defined ALL subtypes of all or age‐related patient groups. HLA‐A, ‐B, or ‐DR antigens, as well as HLA‐ABC three‐locus haplotypes were similarly distributed in patients and their local or Caucasian controls. The results indicate HLA‐linked genetic factors conferring susceptibility to ALL in adults, particularly those presenting with B‐, T‐, and Null‐ALL.
Restriction fragment polymorphisms of the HLA‐DR, HLA‐DQ, and insulin gene regions in IDDM: The GAW5 data
Authors: Cox N. J. , Gogolin K. J. , Horvath V. J. , Barker D. F. , Wright E. , Tran T. , Skolnick M. H. , Boehm B. O. , Fehsel K. , Bertrams J. , Hodge T. W. , Acton R. T. , McGill J. , Elbein S. C. , Permutt M. A. , de Préval C. , Avoustin P. , Cambon‐Thomsen A. , Robinson D. M. , Holbeck S. L. , Nepom G. T. , Schneider P. M. , Rittner C. , Toyoda H. , Rotter J. I. , Spielman R. 
Published: June 2005

AbstractThe primary aim of the insulin‐dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5) was to collect and analyze new data on DNA polymorphisms closely linked to the HLA‐D region and the insulin gene. The probes and restriction enzymes described here were used by all ten participating labs, and the data from Southern blotting were interpreted and reported according to conventions developed for the Workshop. These DNA data on members of 94 families with two or more IDDM sibs constitute the largest such sample available. The data were used in most of the analyses presented at the Workshop meeting, and are available on request.
Immunoglobulin allotyping (Gm, Km) of GAW5 families
Authors: Field L. Leigh , Dugoujon Jean‐Michel 
Published: June 2005

AbstractThe following Gm and Km immunoglobulin allotypes were determined on the Genetic Analysis Workshop 5 insulin‐dependent diabetes mellitus (GAW5 IDDM) families: Glm (1,2,3,17), G2m (23), G3m (5,10,11,13,14,21,28) and Km (1,3). Since the allotype G2m (23) has been rarely studied, due to paucity of typing reagents, it was of interest to compare the frequency of the halotype encoding this allotype in parents of North American GAW5 IDDM families with the frequency found in a previous investigation of healthy North Americans. Results indicated very similar frequencies of Gm haplotypes in the two groups.
Charateristics of a multiplex IDDM sample: Unexplained differences with other samples
Authors: Falk Catherine T. 
Published: June 2005

AbstractCharacteristics of a multiplex sample of families with insulin‐dependent diabetes mellitus (IDDM) are studied and contrasted with similar characteristics in other, more conventionally sampled data sets. Some characteristics remain consistent with earlier observations including the high frequency of human leukocyte antigen (HLA) DR3,4 in affected individuals and the greater than expected percentage of HLA haplotype sharing among affected sib pairs. In other respects, however, differences are seen between this sample and others. “Control” haplotypes, i.e., those not transmitted to the first affected offspring, had a higher frequency of DR3 and DR4 than expected, and a rather high frequency of affected parents was observed. Differences between the first affected and later affected offspring reported in other samples were absent from these families. No effect of the sampling scheme and the resulting distribution of parental phenotypes could be shown to explain this difference.
Genes predisposing to IDDM in multiplex families
Authors: Field L. Leigh 
Published: June 2005

AbstractAnalysis of HLA haplotypes occurring in more than one, only one, or no diabetics in GAW5 multiplex insulin‐dependent diabetes mellitus (IDDM) families suggested: (1) DR3, DR4, DRw6, and DRw8 are positively associated, and DR2 is negatively associated, with IDDM; (2) DR4 haplotypes are more diabetogenic than DR3 haplotypes; some DR3 haplotypes lacking B8/B18 are more diabetogenic than those carrying B8/B18; DR3 haplotypes with DRβ TaqI bands [2,5,10/11] are more diabetogenic than those without; DR4 haplotypes that carry DQw3.2 are more diabetogenic than those that do not; some DR2 haplotypes are diabetogenic rather than protective. Analysis of DR3 and DR4 transmission from DR3/X and DR4wX (X ≠ 3,4) healthy parents suggested: (3) no distortion of transmission to healthy children and (4) mothers transmit DR4 (and perhaps DR3) less often than fathers to diabetic children. Analysis of INS, GM, and HLA haplotype sharing in affected sib pairs suggested: (5) random segregation of INS haplotypes and (6) a tendency to increased sharing of GM haplotypes in affected sib pairs who were HLA‐identical and DR3/4, compared with pairs who were not.
Association and sibpair analysis for the HLA, Gm, Km, and insulin polymorphisms in multiplex IDDM families
Authors: Fimmers R. , Neugebauer M. , Dennert J. , Wienker T. , Baur M. P. 
Published: June 2005

AbstractA log‐linear model was used to analyze three‐way interactions between IDDM and pairs of genetic markers. To do this, a special sample dataset was selected by taking one affected and one unaffected child from each family. Some three‐way interactions were found for associations between insulin‐dependent diabetes mellitus (IDDM), HLA‐DR, and DQ restriction enzyme fragment length polymorphism (RFLP) patterns. No three‐way interaction was found for IDDM, HLA‐DR, and Gm or Km. An extended sibpair analysis was applied to the HLA‐B,DR loci and to the Gm, Km, and insulin gene polymorphisms. The well‐known result for IDDM and HLA was reproduced. For Gm, Km, and the insulin gene no cosegregation with IDDM could be found.
Genetic analysis of the affective disorders: Summary of GAW5
Authors: Rice John , Risch Neil 
Published: June 2005

AbstractParticipants in the Affective Disorders component of Genetic Analysis Workshop 5 had acces to five distributed data sets: (1) 187 families from the Collaborative Depression Study, (2) 202 families ascertained as part of the NIMH Family Studies on Affective Disorders, (3) a compilation of 46 pedigrees informative for X‐linked markers, (4) HLA typing on 116 kindreds from the Toronto‐Rochester Depression Study, and (5) 81 members of an Old Order Amish pedigree demonstrating linkage to markers on chromosome 11p. These databases are each summarized after a brief account is given of the genetics of the affective disorders and commonly used diagnoses.The emphasis of the Workshop was methodologic, with contributions divided evenly between linkage and nonlinkage applications. Contributions are summarized under four substantive areas: regressive logistic models, segregation and other familial analyses, methodologic considerations in linkage analysis, and the relationship between HLA and affective disorders.
Linkage data on affective disorders in an epidemiologic context
Authors: Gershon Elliot S. , Goldin Lynn R. 
Published: June 2005

AbstractRecent data on chromosomal linkage markers in affective disorders indicate that single locus inheritance is involved in these disorders. The presence of a single locus has not been detectable using segregation analysis on family study data from large populations, possibly because of both heterogeneity and birth cohort and sex differences in diagnostic frequencies.
The incomplete, multiple ascertainment model: Assumptions, applications, and alternative models
Authors: Stene Jon 
Published: June 2005

AbstractAssumptions and applications of the widely used incomplete, multiple ascertainment model have been examined. The common use of a reduced version of the model by suppressing the information about independently ascertained probands leads to inaccurate and unstable estimates. The fact that many samples consist mainly of families ascertained through the first member who has the disorder may lead to seriously biased estimates of the segregation probability, as the model does not take this common ascertainment situation into account.
Linkage analysis under “random” and “genetic” reduced penetrance
Authors: Greenberg David A. , Hodge Susan E. 
Published: June 2005

AbstractWe examined whether the results of linkage analysis are affected by the reasons for so‐called “reduced penetrance”. We simulated linkage data with random reduced penetrance and contrasted that with data that were simulated under inheritance controlled by two loci interacting epistatically. For the two‐locus disease models, one of those loci was linked to the marker. All data, irrespective of how the data were simulated, were analyzed under the assumption of a single‐locus genetic model with random reduced penetrance. We found that there appears to be little bias in the results of linkage analysis whether the “reduced penetrance” was caused by random (usually interpreted as environmental) factors or by strictly genetic factors. We also illustrate that when the trait or disease is influenced by more than one locus, the inheritance of the trait at the linked locus is the important consideration, not the inheritance of the trait per se.
Analysis of the Toronto‐Rochester depression study follow‐up data confirms an HLA‐region gene contribution to susceptibility to affective disorder
Authors: Weitkamp L. R. , Stancer H. C. 
Published: June 2005

AbstractAnalysis of HLA haplotype distributions in relation to major affective disorder in affected sibling pairs and affected aunt or uncle and niece or nephew pairs confirmed that HLA‐region genes do contribute to susceptiblity to affective disorder. The data indicated that this effect may be greater in unipolar than in bipolar disorder, and more apparent in families with few affected members than in heavily loaded families. Nonrandom assortment of HLA haplotypes to affected and unaffected offspring in “low load” families occurred principally for the haplotype transmitted from the side of the family without affective disorder. We conclude that HLA‐region genes contribute to but are not the only factor in susceptibility to major depression.
Phenylthiocarbamide taste sensitivity revisited: Complete sorting test supports residual family resemblance
Authors: Reddy B. M. , Rao D. C. , MacCluer Jean W. 
Published: June 2005

AbstractPhenylthiocarbamide (PTC) taste thresholds were determined in 100 nuclear families using the complete sorting test. Segregation analysis using the mixed model suggested that the variability in PTC thresholds is controlled by a major locus with incomplete dominance as well as by a multifactorial component with significant residual heritability. Such a model explained nearly 96% of the variance, leaving only 4% of the variance in thresholds arising from measurement error and other environmental factors.
Simulation of Huntington's disease onset
Authors: Markson Leona Enama , Chase Gary A. , Brookmeyer Ron , Rao D. C. 
Published: June 2005

AbstractPrevious investigators have noted that the type of sampling scheme used to study the natural history of Huntington's disease can affect the observed age of onset distribution. Simulated data are presented to demonstrate that bias is introduced when onset characteristics derived from prevalence samples (i.e., samples of affected individuals alive in the population) are used to evaluate cofactors of disease onset and to compute genetic risk estimates for persons “at risk” of developing the disease. This study demonstrates that prevalence sampling underestimates the proportion of Huntington's disease cases in the population with later onset ages. Using plausible values for onset time, duration, and life expectancy, simulation results suggest that the paternal transmission effect on Huntington's disease onset is overestimated when based on prevalence data.
The impact of altered fitness on the risk of illness in relatives
Authors: Kendler Kenneth S. , Maclean Charles J. , Rao D. C. 
Published: June 2005

AbstractAltered fitness of affected individuals can substantially influence the pattern of risk of illness in relatives. This altered risk can result from both changes in the distribution of genotypes and changes in the genotype‐spcific proportion affected or GSPA. This report examines the impact of altered fitness on the GSPA in relatives of affected probands, under a simple genetic model. The model assumes that illness results from a generalized single major locus and that fitness is dependent only upon phenotype. It is shown that i) in progenitors of probands (e.g., parents and grandparents), GSPA can vary widely as a function of the fitness of affected individuals; ii) the change in GSPA is equal in parents and grandparents; and iii) in non‐progenitors (e.g., offspring, siblings, uncles/ aunts), GSPA is independent of fitness effects. The GSPA in parents and grandparents is a function both of the relative fitness of affected individuals (F) and the penetrance (Q) that can be approximated by the simple formula: GSPA = FQ/(FQ + 1 − Q). The successful application of model‐fitting methods for the detection of single gene variation to complex phenotypes that significantly alter fitness may, in certain circumstances, require the incorporation of “fitness effects” into the analytic model.
Phenotypic effects of apolipoprotein structural variation on lipid profiles: II. Apolipoprotein A‐IV and quantitative lipid measures in the healthy women study
Authors: Eichner J. E. , Kuller L. H. , Ferrell R. E. , Kamboh M. I. , Rao D. C. 
Published: June 2005

AbstractApolipoprotein A‐IV (APO A‐IV) is a major protein component of mesenteric lymph chylomicrons and very‐low‐density lipoproteins. It is found in plasma predominantly unassociated with major lipoprotein fractions and in high density lipoproteins. APO A‐IV exhibits structural heterogeneity owing to two codominant alleles, APO A‐IV*1 and APO A‐IV*2, that occur in Caucasian and black populations. In vitro experimental evidence indicates that APO A‐IV may be a cofactor for the lecithin:cholesterol acyltransferase enzyme, may be involved in reverse cholesterol transport, and may play an important role in the modulation of lipoprotein lipase activity. In this study we have investigated the effect of two APO A‐IV phenotypes, APO A‐IV 1–1 and APO A‐IV 2–1, on quantitative lipid measures in a group of 453 white women being followed through menopause for changes in cardiovascular risk. At baseline all women were premenopausal. Of the nine lipid measures, triglycerides showed a marginally significant effect caused by phenotype. The APO A‐IV 2–1 heterozygotes had lower average triglycerides than the 1–1 homozygotes (P = .053).
Increased risk for gestational diabetes mellitus associated with insulin receptor and insulin‐like growth factor II restriction fragment length polymorphisms
Authors: Ober Carole , Xiang Kun‐San , Thisted Ronald A. , Indovina Kelly Andrew , Wason Candace J. , Dooley Sharon , Rao D. C. 
Published: June 2005

AbstractGestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. We have examined restriction fragment length polymorphisms (RFLPs) near “candidate diabetogenic genes” as one approach to identify molecular markers for GDM genes. Genotypes for insulin hypervariable region (HVR), insulin‐like growth factor II (IGF2), insulin receptor (INSR), and glucose transporter (GLUT1) RFLPs were studied in 96 GDM and 164 control subjects, matched to GDM for race, age, and gravidity. Logistic regression analysis was used to explore the relationship between genotypes at these candidate gene loci and GDM, while adjusting for the effects of potential confounding variables. Among black subjects, the INSR allele 1 (P = 0.001) and interactions between INSR allele 1 with body mass index (BMI) (P = 0.002) and history of DM in subject's mother (P = 0.004) contributed significantly to GDM risk. Among Caucasian subjects, a similar relationship between the INSR allele 1 (P = 0.007) and INSR allele 1—BMI interactions (P = 0.011) on GDM risk were observed. In Caucasians, an additional significant risk factor was determined by an INSR allele 1—IGF2 allele 2 interaction (P = 0.018). No risk factors were identified in Hispanic subjects. These data continue to support the hypothesis that GDM is a heterogeneous disorder with respect to phenotypic and genotypic features. Furthermore, our data suggest that risk for GDM in black and Caucasian subjects is not due to obesity per se but to interactions between obesity and INSR alleles. In Caucasian women, INSR and IGF2 alleles interact to confer additional risk for GDM. Thus genes underlying susceptibility to GDM in some women may be similar to genes conferring risk to NIDDM, while in others novel genes may contribute to GDM risk.
Importance of hereditary disease at a Neuropsychiatric Institute in Mexico City
Authors: Alonso M. E. , Gomez L. , Otero E. , Figueroa H. H. 
Published: June 2005

AbstractThe objective of this study is to investigate the type, importance, and incidence of hereditary diseases in patients at the National Institute of Neurology and Neurosurgery in Mexico City. A review of 6,258 files indicated that hereditary diseases represent an important problem for the Institute: Of the diseases with the highest incidences, hereditary factors have an important role in seven (epilepsy, depression, facial palsy, schizophrenia, mental retardation, migraine, and Parkinson's disease). Diseases of known monogenic etiology represent 1.5% of all the cases.
Major gene polymorphism for human erythrocyte (RBC) thiol methyltransferase (TMT)
Authors: Price Richard Arlen , Keith Richard A. , Spielman Richard S. , Weinshilboum Richard M. , Vogler G. P. , Rao D. C. 
Published: June 2005

AbstractThiol S‐methylation is an important pathway in the metabolism of many sulfhydryl compounds including the antihypertensive drug captopril and the antirheumatic medication D‐penicillamine. Erythrocyte (RBC) thiol methyltransferase (TMT) activity was measured in blood samples from 237 individuals from 49 nuclear families. Earlier studies have demonstrated familial aggregation of RBC TMT activity, suggesting a role for genetic determinants. Our study indicates the specific mode of inheritance and gives relative contributions of a major locus and background genotype. We found evidence for a major locus, TMT. The aliele frequencies for low enzyme activity, TMTL, and high activity TMTH, estimated from a power transformed scale were 0.58 and 0.42, respectively. The high activity allele, TMTH, appears to have reduced expression in heterozygous individuals (d = 0.21) and to act in concert with a strong influence from polygenic genotype (H = 0.75) to produce a highly heritable phenotype. This major gene polymorphism may now be studied using biochemical and molecular genetic techniques.
Bivariate survival models for analysis of genetic and environmental effects in twins
Authors: Thomas Duncan C. , Langholz Bryan , Mack Wendy , Floderus Birgitta , Rao D. C. , Vogler G. P. 
Published: June 2005

AbstractClassic methods in genetics for the analysis of binary attributes, based on an assumption of a “threshold” on a normally distributed latent variable called “liability,” estimate the strength of genetic and environmental effects from differences in correlations between relatives of differing genetic relatedness. Two problems that are not easily addressed by these methods are the need to take the age of onset into account (particularly in chronic diseases in which incidence rates vary considerably with age and the lengths of time at risk can vary between individuals) and the desirability of incorporating measured covariates (genetic or environmental). The standard methods of cohort analysis used in epidemiology allow for both of these features, but until recently have been restricted to independent individuals. Recent developments in survival analysis have extended the widely used “proportional hazards” model of Cox by the addition of latent variable, ε, reflecting the shared susceptibility of related subjects because of their shared genes or shared environment. We show how this approach can be combined with more traditional models of gene–environment interaction to allow the main effects of measured genetic markers and environmental variables to be estimated, as well as the residual variance of genetic and environment and their interactions. The approaches are applied to a cohort of female twin births in Sweden from 1886 to 1958, linked with the Swedish cancer registry from 1961 to 1982.
On the asymptotic behavior of the estimate of the recombination fraction under the null hypothesis of no linkage when the model is misspecified
Authors: Williamson John A. , Amos Christopher I. 
Published: June 2005

AbstractWe show that under the null hypothesis of no linkage the maximum likelihood estimator of the recombination fraction converges to 1/2 even when the trait‐related parameter values in the likelihood function are misspecified. Furthermore, we show that under the null hypothesis of no linkage, but with misspecified trait‐related parameter values, the negative of twice the natural logarithm of the likelihood ratio statistic still has a limiting chi‐square distribution with 1 degree of freedom.