bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic epidemiology of Menkes disease
Authors: Horn Nina , Morton Newton E. , Rao D. C. 
Published: June 2005

AbstractCopper incorporation studies were performed on individuals from 58 pedigrees, comprising 140 sibships. As previously reported, there is considerable overlap between heterozygotes and normal homozygotes. Segregation analysis supports recessive inheritance of disease, with residual heritability for 64Cu uptake in cultured cells. The population frequency of sporadic cases is compatible with the 1/3 expected for an X‐linked lethal with equal mutation rates in egg and sperm, which implies a mutation rate of 6.7 × 10−6/gamete/generation. The parameters estimated here are likely to provide the best basis for genetic counseling until more reliable carrier tests are performed on a systematic sample from a large, defined population.
Description of a large pedigree with an adverse lipoprotein cholesterol phenotype: The Bogalusa Heart Study
Authors: Rosenbaum Peter A. , Amos Christopher I. , Shear Charles L. , Elston Robert C. , Sellers Thomas A. , Srinivasan Sathanur R. , Berenson Gerald S. , Rao D. C. 
Published: June 2005

AbstractA large pedigree (N = 356) with a high prevalence of heart disease and associated adverse lipoprotein phenotype was studied. The adverse lipoprotein phenotype is characterized by both low levels of high‐density‐lipoprotein cholesterol (HDL‐C) alone (16.3%) and in combination with other adverse lipoprotein levels (12.8%). In all, 44.2% of all pedigree members had at least one adverse lipoprotein level. Analysis of mating types showed that all lipids and lipoproteins possess familial clustering with 25–36% of offspring above median levels when both parents had levels below the median, while 67–83% had levels above the median when both parents had levels above the median. Using adjusted lipid and lipoprotein levels, a statistically significant linear trend was found between the degree of relationship to pedigree members with heart disease, and both the low‐density‐lipoprotein cholesterol/high‐density‐lipoprotein cholesterol (LDL‐C/HDL‐C) ratio (P < .05), and the very‐low‐density‐lipoprotein cholesterol (VLDL‐C; P < .01) level. A similar analysis using the prevalence of adverse lipoprotein levels as the dependent variable and degree of relationship to heart diseased pedigree numbers as the independent variable showed significant (P < .05) relationships with VLDL‐C and the LDL‐C/HDL‐C ratio. Further genetic analyses of this pedigree may reveal genetic mechanisms responsible for the familiality of lipoprotein levels in this pedigree.
Linkage analysis of Von Recklinghausen neurofibromatosis: Chromosomes 4 and 19
Authors: Dietz Jeanne N. , Robbins Tim , Cannon Lisa A. , Schwartz Charles E. , Carey John C. , Johnson John P. , Kivlin Jane , Skolnick Mark H. , Rao D. C. 
Published: June 2005

AbstractThis report describes a study that examines the hypotheses of genetic linkage between the autosomal dominant disorder neurofibromatosis (NF) and loci on human chromosomes 4 and 19. Twelve Utah families were evaluated for evidence of possible linkage of NF to six known markers on chromosome 4 and five markers on chromosome 19. Due to previous reports suggesting tight linkage of NF to the GC locus on chromosome 4 and the C3 (linked to myotonic dystrophy) locus on chromosome 19, these two markers were of particular interest. For the Utah families the cumulative LOD score for GC was −4.81 (r̂ = 0.05). Cumulative LOD scores were −0.90 (r̂ = 0.05) and −1.01 (r̂ = 0.05) for C3 serum determinations and a C3 DNA polymorphism respectively. Linkage data is also included on all individual informative families for the GC and C3 loci to specifically address the question of heterogeneity. Linkage data is consistent with, but does not strongly support, the existence of heterogeneity implicating both the GC locus on chromosome 4 and the C3 locus on chromosome 19. A compilation of cumulative LOD scores from this and other current linkage studies produces values that in the absence of heterogeneity refute previous reports for tight linkage of NF to GC and to C3.
Estimation of linkage disequilibrium from conditional haplotype data: Application to β‐globin gene cluster in American blacks
Authors: Chakraborty Ranajit , Rao D. C. 
Published: June 2005

AbstractSimple estimators of gene frequencies and linkage disequilibria are proposed when haplotype data are available from four parental chromosomes of a child (or fetus) for whom genetic counseling is sought for a disease condition. The method is illustrated with restriction site polymorphisms associated with sickle‐cell anemia (Hb‐βS) gene as surveyed in genetic counseling data from American blacks. The method suggested here is shown to be useful in testing for the significance of interactions of site‐specific variations of any order in the chromosomal region assayed.
Multiple regression analysis of twin data obtained from selected samples
Authors: LaBuda Michele C. , Defries J. C. , Fulker D. W. , Rao D. C. 
Published: June 2005

AbstractThe multiple regression analysis of twin data in which a cotwin's score is predicted from that of a proband (the member of a twin pair selected because of a deviant score) and the coefficient of relationship provides a powerful test of genetic etiology (DeFries and Fulker: Behav Genet 15:467–473, 1985). Moreover, when an augmented model containing an interaction term is fitted to the same data set, direct estimates of heritability (h2) and the proportion of variance owing to shared environmental influences (c2) are also obtained. In the present paper, the expected partial regression coefficients estimated from these models are derived, and the flexibility of the general approach is illustrated. An extended model is formulated for the analysis of data from combined samples of affected and control twin pairs that yields tests for differential h2 and c2 in the two groups as well as pooled estimates of these parameters. The application of these models is illustrated by an analysis of data from reading‐disabled and control twin pairs. Because of the ease, flexibility, and utility of the multiple regression analysis of twin data, it is an appealing alternative to more traditional model‐fitting approaches.
Goodness‐of‐fit tests for locus order in three‐point mapping
Authors: Ott Jurg , Lathrop G. Mark , Rao D. C. 
Published: June 2005

AbstractFor the case of three‐point linkage analysis, a simple goodness‐of‐fit test is proposed to test the order of gene loci. To use it for testing one locus order against another, one may apply the principle that evidence for one order comes from lack of fit of the observations to the other order. With n = 30 offspring from a phase known triple backcross mating, at a recombination fraction of 20% between adjacent loci, the test achieves a power of 80% (5% significance level). Interference (real interference as well as interference assumed in the analysis) increases power.
Apolipoprotein genetic variation in the assessment of atherosclerosis susceptibility
Authors: Hegele Robert A. , Breslow Jan L. , Cloninger C. Robert 
Published: June 2005

AbstractApolipoproteins are the protein constituents of lipoproteins, the particles that transport cholesterol and triglycerides in the plasma. Numerous epidemiologic studies have associated variations in plasma levels of lipoproteins and apolipoproteins with the development of atherosclerosis. Furthermore, genetic variations in lipoproteins and apolipoproteins have been associated with disorders of lipid metabolism. Recent advances in biochemical and molecular genetic methods have resulted in an increased understanding of interindividual variations in lipoprotein metabolism and of their relationship to atherosclerosis and the dyslipoproteinemias. In particular, certain DNA restriction fragment length polymorphisms of the apolipoprotein genes have, in the last few years, been associated with atherosclerotic diseases and dyslipoproteinemias. We believe that genetic markers, when used in conjunction with traditional clinical and biochemical determinations, may one day be useful in predicting atherosclerosis susceptibility in the general population.
Endogenous sex hormone levels and breast cancer risk
Authors: Begg Lisa , Kuller Lewis H. , Gutai James P. , Caggiula Arlene G. , Wolmark Norman , Watson Charles G. , Rao D. C. 
Published: June 2005

AbstractSex‐steroid hormones are a major determinant of the risk of breast cancer. We evaluated the relationship between obesity and endogenous estrogen levels in 79 healthy, postmenopausal women. Thirty‐nine of the women were siblings of patients with postmenopausal‐onset breast cancer; the remaining women were age matched (± 10 yr) controls. Our hypothesis was that the siblings of the breast cancer patients would weigh more and that this excess weight would lead to higher serum estrone levels. The choice of unaffected family members of breast cancer patients reduces the concern that results may have been influenced by the cancer rather than antecedent to its development. Our findings demonstrated a statistically significant excess estrone level in the siblings compared to the controls (58.9 vs 47.8 pg/ml, P=0.005). The siblings weighed 4.3 kg more than the controls. Matched pairs analysis (sibling—control), adjusting for weight, also showed significant differences in serum estrone levels. These differences were observed despite comparability in dietary intake, medication use, and personal medical history. These findings represent the first time that higher estrogen levels have been measured in siblings of postmenopausal breast cancer patients. This observation may represent an important link in our understanding of the relationship between genetic and environmental risk factors of breast cancer. One approach to subsequent genetic studies of breast cancer may be to focus on the possible biological determinants such as sex‐steroid hormone level receptors, oncogenes, and gene products and not on the “familial aggregation” of breast cancer.
Classification of rheumatoid arthritis: The importance of including data from the siblings
Authors: Walker D. J. , Stephenson A. M. , Griffiths I. D. , Roberts D. F. , Rao D. C. 
Published: June 2005

AbstractA discriminant analysis has been applied to physical and laboratory data on a series of 37 patients with rheumatoid arthritis (RA). Good discrimination was found between RA when it was associated with organ‐specific autoimmune phenomena and when it was not. When data from other members of the families was included there was consistently better discrimination than when using data from the patients alone. The results suggest that future studies of classification of variable diseases should include study of relatives.
Tests of linkage and heterogeneity in Mendelian diseases using identity by descent scores
Authors: Chakravarti Aravinda , Badner Judith A. , Li Ching Chun , Rao D. C. 
Published: June 2005

AbstractWhen linkage between a recessive Mendelian disease and specific candidate genes is investigated, identity by descent scores in affected sib pairs may be used for tests of linkage and heterogeneity. Statistical tests for performing this analysis are presented. The efficiency and statistical power of the method are also investigated using computer simulations.
Sporadic vs familial classification given etiologic heterogeneity: I. Sensitivity, specificity, and positive and negative predictive value
Authors: Kendler Kenneth S. , Cloninger C. R. 
Published: June 2005

AbstractEnvironmental factors are etiologically important in many non‐Mendelian familial disorders in man. Because such disorders often occur as “sporadic” cases, (ie, an affected individual with no affected relatives), it is tempting to assume that such cases represent an “environmental” form of the disorder. This paper presents an evaluation of the sensitivity, specificity, and positive and negative predictive power (PPV and NPV) of this “sporadic vs familial classification.” The model assumes etiologic heterogeneity with a subpopulation of cases due to a “major” environmental event acting independent of genotype and the remaining cases resulting from a generalized single major locus (SML). Sibship size is modeled by a truncated negative binomial distribution. For rare disorders, this classification has high sensitivity and NPV but low specificity and PPV. As the disorder becomes more common, sensitivity and NPV fall while specificity and PPV rise. The power of the method increases substantially with increasing sibship size up to four or five, but further increases in power are minimal. MZ twins add considerable power to the method but aunts and uncles add little if anything. Both a correlational (phi) and an agreement‐based (kappa) statistic indicate that, under most realistic circumstances, the relationship between etiology and family history is modest.
Nonrandom sampling in genetic epidemiology: Maximum likelihood methods for multifactorial analysis of quantitative data ascertained through truncation
Authors: Rao D. C. , Wette R. , Eaves Lindon J. 
Published: June 2005

AbstractThree types of nonrandom sampling of family data are described, and appropriate maximum likelihood methods are proposed for each. The three types arise depending on whether the selection of probands, based on truncation, is applied directly to the phenotypic distribution, to the distribution of a correlated trait, or to the liability distribution of an associated disease. Family data ascertained through random and nonrandom sampling can be analyzed together in a unified approach. Results of a Monte Carlo study are presented that demonstrate the utility of the proposed methods. In particular, likelihood ratio tests of null hypotheses are shown to be distributed as chi‐square, even in samples as small as 50 families (with variable sibship size).
Exclusion of autosomal dominant dystonia gene from large regions of chromosomes 11p, 13q, and 21q by multi‐point linkage analysis
Authors: Kramer P. L. , Ozelius L. , Gusella J. F. , Fahn S. , Kidd K. K. , Breakefield X. O. , Boerecki I. B. 
Published: June 2005

AbstractMulti‐point linkage analyses of autosomal dominant form of torsion dystonia with linkage groups on chromosomes 11p, 13q, 21q are reported. Analyses are based on family data from a single, large, non‐Jewish pedigree. Large portions of chromosomes 11p and 13q, and virtually the entire long arm of chromosome 21 are excluded from linkage with dystonia. Practical aspects of designing multipoint analyses are discussed.
Power of the affected‐sib‐pair method for heterogeneous disorders
Authors: Goldin Lynn R. , Gershon Elliot S. , Borecki I. B. 
Published: June 2005

AbstractWe have examined the sample sizes required to detect linkage using the affected‐sib‐pair (ASP) method for major psychiatric disorders that are characterized by population prevalences of 1–7%, decreased penetrance, phenocopies, and heterogeneity. In addition, the nature of these illnesses makes large, multigenerational pedigrees difficult to collect. We calculated the sample sizes needed to have 80% power of finding linkage (with a type I error rate of 5%) under dominant and recessive models with incomplete penetrance and allowing for recombination rates of up to 10% between the disease gene and marker gene. We have assumed that the identical‐by‐descent (IBD) status of ASPs is known exactly. For a disease like schizophrenia (1% population prevalence), if 50% of families are linked to a marker locus at 10% recombination, then 60 and 120 pairs are needed under recessive and dominant inheritance, respectively. For a disorder such as major affective disorder (7% population prevalence), the sample size is similar if the inheritance is recessive, but larger (160 pairs) if the inheritance is dominant. We conclude that this method may be a reasonable alternative for psychiatric disorders, especially to confirm that a linkage found in a specific pedigree or population isolate is also present in the general population.
Segregation analysis of juvenile myoclonic epilepsy
Authors: Greenberg David A. , Delgado‐Escueta Antonio V. , Maldonado Hector M. , Widelitz Heidi , Rao D. C. , Borecki I. B. 
Published: June 2005

AbstractWe examined the inheritance of juvenile myoclonic epilepsy (JME). We looked at both the trait of “epilepsy” and the trait of “epilepsy‐plus‐EEG abnormalities”, since EEG abnormalities are frequently found in the clinically unaffected sibs of JME patients. We tested several modes of inheritance including the fully penetrant recessive and several two‐locus models. We could reject all models tested (fully penetrant single‐locus and two‐locus models) when abnormal EEGs were classified as “unaffected”. We could also reject the fully penetrant single locus models when family members with abnormal EEGs were considered “affected”. We also rejected the two‐locus model where the inheritance at both loci was dominant. The two‐locus model where both loci showed recessive inheritance could not be rejected, nor could the model where one locus was dominant and the other recessive. Our results suggest that the underlying predisposition for JME is genetically determined and is partially reflected in the abnormal EEGs found in clinically unaffected family members.
Linkage information and bias in the presence of interference
Authors: Bishop DT , Thompson EA , Rao D. C. 
Published: June 2005

AbstractAlthough interference is an important biological phenomenon, linkage analyses often ignore it for computational efficiency. In this paper we examine the effects of ignoring interference on estimates of recombination fraction, and the power of statistical tests to detect interference. We show that for gametes from phase‐known triple heterozygotes, no bias in the recombination fraction for adjacent loci results from the assumption of lack of interference even if interference is present. However, for samples from pairwise informative samples, there is bias introduced. An analytical form for this bias is obtained.
Some biological and social factors of risk associated with the birth of pre‐term infants
Authors: Livshits G. , Davidi L. , Kobyliansky E. , Levi Y. , Ben‐Amitai D. , Merlob P. , Rao D. C. 
Published: June 2005

AbstractThe main purpose of the present study was to evaluate the effects of factors associated with spontaneous pre‐term births so that the high risk woman could be identified before or at early stages of pregnancy. For this purpose, we have compared the measurements of 21 anthropometric traits and mean fluctuating asymmetry over 8 bilateral anthropometric traits, as well as age, occupation, education, previous obstetric history, complications during pregnancy, medicines received during and after pregnancy and some others in women who delivered babies of short (26–36 wk, n = 113 ind.) and normal gestational age (n = 103). Diseases and mean fluctuating asymmetry of eight morphological traits in the newborn infants themselves were also studied.Both univariate and multivariate analyses were carried out and these were in agreement, showing a highly significant increase in the morbidity rate (especially of respiratory diseases) among pre‐term infants and in complications during pregnancy in their mothers. Among other variables associated with the current pre‐term birth were previous spontaneous pre‐term births, suggesting their special risk value. The estimate of the sib correlation in gestational age on the liability scale was about 0.63. Spearman and Pearson correlations in gestational age for siblings were 0.34 and 0.31, respectively.
Cell surface markers and cellular immune response associated with rheumatic heart disease: Complex segregation analysis
Authors: Rich SS , Gray ED , Talbot R. , Martin D. , Cairns L. , Zabriskie JB , Braun D. , Regelmann WE , Vogler G. P. 
Published: June 2005

AbstractA series of functional and cell surface markers associated with a significantly increased risk of rheumatic heart disease were analyzed for the contribution of genetic factors in their presence. Peripheral blood lymphocytes from nine large kindreds from the New Zealand Maori, Polynesian, and Caucasian populations were isolated, purified, and evaluated with lymphocyte surface markers (monoclonals 83S.19.23 and D8103), as well as studied for blastogenic response to a purified group A streptococcal extracellular product, blastogen A. Segregation analysis of blastogenic response and percent of cells positive for these cell surface markers was consistent with genetic control by single major genes; however, the contribution by polygenes varied by marker, indicating heterogeneity of genetic control of identification of cell surface glycoproteins and blastogenic response to streptococcal products.
Genetic analysis of IDDM: Summary of GAW5 IDDM results
Authors: Spielman Richard S. , Baur Max P. , Clerget‐Darpoux Françoise 
Published: June 2005

AbstractThis paper summarizes the analyses by participants in the insulin‐dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5). The data were obtained from 94 families with two or more IDDM sibs. Topics treated in the Workshop analysis included the following: methods for detecting associations and linkage, the contribution by HLA‐linked and ‐unlinked loci to IDDM susceptibility, the role of subtypes of the serologically defined HLA specificities, the implications of associated diseases other than IDDM in the families, the significance of antibodies to Coxsackie viruses, and of autoantibodies to pancreatic islet cells and insulin, and the use of genetic models to analyze the inheritance of IDDM.There was agreement that an explanation for the data on multiplex IDDM families must include the following features: (1) There is a susceptibility locus (or loci) in the HLA region. (2) The HLA‐linked factor(s) are more complex than a single licus with one disese and one nondisease allele. (3) There is additional familial correlation beyond that explained by HLA‐linked susceptibility, which may be genetic and/or environmental.With regard to the third feature, IDDM‐GAW5 included data on variation in Gm haplotypes and at the insulin gene, two regions unlinked to HLA. However, there was no direct evidence (i.e., from marker segregation) that the additional factor, if genetic, is linked to either Gm or the insulin gene. Nevertheless, a significant difference was found between “diabetic” and “control” insulin genes with respect to frequency of class 1 alleles for the 5′ flanking polymorphism, strongly suggesting linkage.
Testing genetic models for IDDM by the MASC method
Authors: Clerget‐Darpoux Françoise , Babron Marie‐Claude 
Published: June 2005

AbstractThe MASC method has been applied to the GAW5 data. The method uses the simultaneous information on association and segregation of the HLA marker with the disease and the segregation of the HLA marker in affected families. It also takes into account the differential risk for parents of a patient, as well as the different HLA haplotype sharing, according to the HLA genotype of the patient. The goodness of fit of several genetic models has been tested. The observed data are not compatible with a two‐allele, one‐locus model, but they fit a three‐allele, one‐locus model and a complementation two‐locus model if additional familial correlation is allowed.