bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex segregation analysis of low levels of plasma high‐density lipoprotein cholesterol in a sample of nuclear families in Jerusalem
Authors: Friedlander Y. , Kark J. D. , Stein Y. , Rao D. C. 
Published: June 2005

AbstractLow levels of high‐density lipoprotein cholesterol (HDL‐C) are associated with increased risk of coronary heart diesease (CHD). Therefore, assessment of the mode of inheritance of HDL‐C is of importance. HDL‐C concentrations in 3,074 nuclear families in the multiethnic Jerusalem Lipid Research Center study population were analyzed for possible involvement of major genes in determination of low levels of this trait. Complex segregation analysis under the mixed model of inheritance (major gene and multifactorial components) was performed on transformed HDL‐C concentrations after adjustment for age, sex, and environmental measures. Evidence for segregation of a recessive major gene for depressed HDL‐C, with an allele frequency of q = 0.06, in addition to multifactorial transmission (H = 0.45) was found in these families. Estimates from the mixed model were homogeneous across the different ethnic groups. When the substantial multifactorial background was excluded from the model, we found evidence for an additive (codominant) Mendelian gene (d = 0.48), which demonstrates the necessity of using the mixed model. Our previous results were inconclusive with respect to the involvement of a major gene in determination of high levels of HDL‐C. However, we tentatively postulate an uncommon recessive gene for low levels of HDL‐C in the Israeli population in addition to polygenic and environmental determinants.
Coagulation factor XIII: Genetic linkage studies with F13B
Authors: Bender Klaus , Bissbort Siegbert , Klein Anne , Mauff Gottfried , Mayerová Antonia , Nagel Marcela , Schilling Annette , Wienker Thomas F. , Rao D. C. 
Published: June 2005

AbstractLinkage relations of the F13B gene with 38 marker genes are analyzed, which, along with the data of earlier reports on the same subject, brings the number of comparisons to a total of 49. Practically all the lod scores are totally negative. This will mean that the F13B gene can hardly be located on the chromosomes/chromosome arms 1p, 2p, 4q, 6p, 14p, 15p, 20q, 21p, 22 and also not on longer segments of 3q, 6q, 7q, 9p, 9q, 11q, 13q, 14q, 16p, and 16q.
Estimation of segregation and ascertainment probabilities by discarding the single probands
Authors: Li C. C. , Chakravarti Aravinda , Halloran Susan L. , Rao D. C. 
Published: June 2005

AbstractThe first portion of this communication reiterates the method of discarding single probands for studying the segregation ratio under incomplete ascertainment. The organization of the algebra leads to the second portion, in which the “self‐contained” subsets are constructed with respect to both the segregation ratio and the ascertainment ratio. These subsets make a more detailed study of segregation and ascertainment possible.
Robust inference for variance components models in families ascertained through probands: II. Analysis of spirometric measures
Authors: Beaty T. H. , Liang K. Y. , Seerey S. , Cohen B. H. , Rao D. C. 
Published: June 2005

AbstractThree spirometric measures of pulmonary function were used to estimate genetic and nongenetic components of variance for 781 members of 158 families ascertained through a proband with obstructive pulmonary disease. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and the ratio of these two (FEV1/FVC) were adjusted for age, sex, race, smoking, and height and used in a robust approach to estimate variance components after conditioning on the proband's observed value. The best fitting model for both residual FEV1/FVC and FEV1 included an additive genetic component representing 25% and 9% of the variation in these two traits, respectively. In addition, there was a significant correlation between parents in residual FEV1/FVC, and a component shared among full sibs was statistically significant for residual FEV1. No evidence of a genetic component for residual FVC was found in this analysis. Although these results agree with previous reports based on other populations in showing a substantial degree of direct genetic control over spirometric measures of pulmonary function, they also raise the possibility of etiologic heterogeneity.
Social selection in human populations: Protected polymorphism of deleterious alleles with incomplete penetrance
Authors: Yokoyama Shozo , Crow James F. 
Published: June 2005

AbstractPopulation dynamics of two alleles, A1 and A2, at a locus under social selection have been studied by considering incomplete penetrance of the three genotypes. A social selection model is constructed by assuming that the fitness of an individual is determined by his or her own phenotype as well as parental phenotypes. For both multiplicative and additive fitness models, sufficient conditions for a protected polymorphism depend on the reduced fitness of affected individuals (γ), the reduced fitness of all individuals resulting from affected parents (β), and the penetrance probabilities, f1, f2, and f3, for the three genotypes, A1A1, A1A2, and A2A2. These conditions reduce to two biologically important cases: 1) f1 < f2 > f3 and β < −γ/(1 − γ) and 2) f1 > f2 < f3 and β > − γ/(1 − γ), and the most common form of the equilibrium frequency of the allele A2 is given by (f1 − f2)/(f1 − 2f2 + f3).
Association between polymorphic blood markers and risk factors for cardiovascular disease in a large pedigree
Authors: George Varghese T. , Elston Robert C. , Amos Chris I. , Ward Laura J. , Berenson Gerald S. , Rao D. C. 
Published: June 2005

AbstractA large pedigree with high prevalence of heart disease is investigated to analyse the association between polymorphic blood markers and quantitative risk factors for cardiovascular disease. The analysis incorporates a familial correlation structure among the individuals in the pedigree and a generalized power transformation to induce approximate residual normality of the risk factors. A total of 380 marker/ risk factor combinations are analysed, and at the nominal 1 % significance level, positive associations are found between the A antigen of the ABO locus and both serum total cholesterol and low‐density lipoprotein cholesterol, and negative associations are found between the B antigen of the ABO locus and serum total cholesterol, and between the B allele of acid phosphatase (AP) locus and systolic blood pressure.
Further tests of nonrandom segregation with special reference to linkage
Authors: Majumder Partha P. , Rao D. C. 
Published: June 2005

AbstractFor an autosomal recessive disease, a statistical procedure is developed for detecting nonrandom segregation of marker haplotypes from an unaffected parent to affected children, specifically for the case when the alternative hypothesis of linkage between the disease and marker loci is postulated. The test procedure is locally most powerful and, depending on family size and number of families sampled, any one of the three test statistics proposed can be used. An application of this procedure provides evidence of linkage between tuberculoid leprosy and HLA.
Etiologic heterogeneity in alcoholism
Authors: Gilligan Sheila B. , Reich Theodore , Cloninger C. Robert , Sing Charles F. 
Published: June 2005

AbstractEtiologic heterogeneity in alcohol abuse was evaluated in 195 extended pedigrees, comprising 288 nuclear families of 140 male and 55 female Caucasian American hospitalized alcoholics. Previous adoption studies in Sweden demonstrated differential heritability of two patterns of alcohol abuse in men: type‐2 alcoholism exhibited early onset of abuse associated with criminal behavior, while type‐1 abuse began at a later age, uncomplicated by antisocial traits. Alcohol abuse in female Swedish adoptees was relatively homogeneous and similar to the lateonset, type‐1 abuse. The notion of etiologic heterogeneity, as suggested by the Stockholm Adoption Studies, was examined in the American pedigrees by contrasting the models of familial transmission of susceptibility to alcoholism obtained via segregation analyses of families of male versus female probands. Families of male probands demonstrated significant familial resemblance, accounted for by a multifactorial‐polygenic background in addition to a major (gene) effect. In contrast, familial resemblance in the pedigrees of female probands was attributed solely to a multifactorial‐polygenic effect. We considered whether some families of male alcoholics were similar to families of female probands, who expressed type‐1 abuse predominantly. Pedigrees of male probands were separated in two groups: (1) “female‐like” families had a better likelihood for the model obtained for families of female probands than the one for families of all male probands, (2) “male‐like” families had a better likelihood for the model of familial transmission describing families of all male probands. A statistically significant difference in the pattern of familial transmission was observed between the “male‐like” and “female‐like” groups. Discriminant function analysis of alcohol‐related symptoms showed that the familial subtypes differed in clinical features as well. Alcohol abuse by male relatives in “male‐like” families was characterized by the early onset of inability to abstain entirely from alcohol or lack of desire to stop drinking; in contrast abuse in “female‐like” families was characterized by late onset of guilt feeling and loss of control over binge drinking.
Genetic epidemiology of duchenne muscular dystrophy in Japan: Classical segregation analysis
Authors: Kanamori Masao , Morton Newton E. , Fujiki Keiko , Kondo Kiyotaro , Rao D. C. , Borecki I. B. 
Published: June 2005

AbstractClassical segregation analysis was performed on 651 male probands in 597 families with Duchenne muscular dystrophy (DMD) collected from 20 of 25 National Institutions for Muscle Diseases in Japan. The proportion of sporadic cases is compatible with 1/3 expected for an X‐linked lethal trait with an equal mutation rate in egg and sperm, the estimated mutation rates being 9.2 × 10−5 and 10.9 × 10−5 /gamete/generation, respectively. The incidence and prevalence among males were estimated to be 29.2 × 10−5 and 6.7 × 10−5, respectively. These results indicated no difference from the patterns of DMD in Western countries.
Inheritance of human platelet thermolabile phenol sulfotransferase (TL PST) activity
Authors: Price R. Arlen , Cox Nancy J. , Spielman Richard S. , Van Loon Jon A. , Maidak Bonnie L. , Weinshilboum Richard M. , Borecki I. B. , Rao D. C. 
Published: June 2005

AbstractSulfate conjugation is an important pathway in the biotransformation of drugs and neurotransmitters. The thermolabile (TL) form of the enyzme phenol sulfotrans‐ferase (PST) catalyzes the sulfation of catecholamine neurotransmitters and drugs such as methyldopa and acetaminophen. Platelet TL PST activity was measured in blood samples from 232 individuals in 49 nuclear families. Correlations ranged from 0.43 to 0.45 for parent–offspring pairs and from 0.44 to 0.47 for siblings. Mother‐father correlations were not significantly different from zero. Although evidence was not unequivocal, both segregation and commingling analyses provided some support for a major gene influence on TL PST activity, with other variation due to polygenic background. In both sets of analyses, however, support for a major gene hypothesis depended upon skewness in the TL PST activity distribution. A polygenic model with high heritability (0.77) was most strongly supported with the log transformed data. These results confirm and extend a previous report of high heritability of TL PST based on a study of twins. In addition, our results raise the possibility of a major gene effect on this important catecholamine‐ and drug‐metabolizing enzyme–a possibility that can now be evaluated using biochemical techniques.
The effect of nutritional factors on sex hormone levels in male twins
Authors: Bishop D. Timothy , Meikle A. Wayne , Slattery Martha L. , Stringham John D. , Ford Marilyn H. , West Dee W. , Borecki I. B. , Rao D. C. 
Published: June 2005

AbstractDietary intake has been hypothesized as being associated with several hormonally related cancers including prostate, breast, ovarian, and endometrial cancer. Because diet may affect hormones directly, it is logical to examine the effects of dietary factors on hormone production and levels. Therefore, a set of 72 male MZ and 83 male DZ twin pairs was ascertained from the Utah birth certificates. A quantitative food frequency questionnaire was administered and blood samples were drawn for hormonal assays. Heritability estimates for hormonal levels were calculated indicating a range from no heritability for sex hormone binding globulin (SHBG), estrone, and testosterone glucuronide to 70% for androstanediol glucuronide and luteinizing hormone. To examine nutritional factors, the difference in hormone and SHBG levels between each MZ twin and his co‐twin were correlated with the difference in nutrient intake. Weight and obesity were significantly correlated with plasma testosterone and follicle stimulating hormone. Fat intake showed a significant association with testosterone. Androstanediol glucuronide, a steroid that reflects tissue formation of dihydrotestosterone, was inversely correlated with caloric intake, theobromine and caffeine. Testosterone glucuronide exhibited significant correlations with calories and vitamin A. This study suggests that dietary intake affects plasma sex‐steroid levels in men.
Cytogenetic studies of couples with repeated spontaneous abortions of known karyotype
Authors: Hassold Terry , Jacobs Patricia A. , Pettay Dorothy , Rao D. C. 
Published: June 2005

AbstractSeveral cytogenetic studies have reported an increased frequency of aneuploidy in peripheral blood cultures of couples with multiple spontaneous abortions. However, in none of the studies have the chromosome constitutions of the fetuses been known, making it difficult to interpret these observations. In the present study, we summarize our cytogenetic observations on 23 couples with multiple miscarriages, 12 of whom had repeated chromosomally normal spontaneous abortions, and 11 repeated trisomic spontaneous abortions. We were unable to demonstrate a significant difference in the level of aneuploidy between the two groups. Therefore, it seems unlikely that aneuploidy detectable in peripheral blood preparations is an important indicator of fetal aneuploidy.
Estimating the age‐at‐onset function using life‐table methods
Authors: Chidambaram A. , Chakravarti A. , Ferrell RE , Lyengar S. , Rao D. C. 
Published: June 2005

AbstractIn the analysis of dominantly inherited diseases, the age‐at‐onset function is often estimated from the observed age‐at‐onset distribution of cases. This estimate is confounded with the age distribution of the population from which the cases were sampled and is accurate only if there are no competing causes of death. In this paper, we present a straightforward method for calculating a more accurate age‐at‐onset function under etiologic heterogeneity. We use the life‐table approach and survival analysis methods. This method is illustrated using data on first‐degree relatives of probands from two sets of families with high cancer incidence: one with breast/ovarian cancer and the other with colon cancer. A comparison of the estimated age‐at‐onset function obtained by the two methods is presented. In both cases, colon cancer as well as breast/ovarian cancer, the estimates of onset probabilities based on proportion of cases, are consistently higher than those obtained by the life‐table method. For breast/ovarian cancer, this difference is not as striking as it is in the case of colon cancer; nevertheless, the method using proportion of cases tends to give a lower estimate of the age‐at‐onset function (higher probability of being affected at lower age) than the life‐table approach.
Lifestyle factors in monozygotic and dizygotic twins
Authors: Heller RF , O'Connell D.L , Roberts DCK , Allen JR , Knapp JC , Steele PL , Silove D. , Rao D. C. , Vogler G. P. 
Published: June 2005

AbstractIn examining genetic influences on biological variables using twins, it may be important to examine the distribution between and within twin pairs of demographic and lifestyle factors that may themselves affect the biological variable being studied. We explored the distribution of demographic and lifestyle factors that may affect blood lipid levels or ischaemic heart disease (IHD) risk among a sample of 106 monozygotic (MZ) and 94 like‐sex dizygotic (DZ) twin pairs. In our sample, MZ twins were statistically significantly different from DZ twins only in marital status, cigarette smoking habits, and the ratio of polyunsaturated to saturated fat (P:S ratio) in their dietary intake. The latter variable was among many dietary variables examined (using 4‐day weighed food diaries), and the size of the difference in intake was small. When comparisons were made of the similarities within twin pairs, we found members of MZ twin pairs to be statistically significantly closer than DZ twins in educational achievement, occupation, cigarette smoking, and exercise habits, and the number of days a week on which alcohol was consumed. These last three variables were consistently closer among twins with closer contact than among those with a smaller degree of current shared environment. For 12 of the 13 nutrients examined, the within‐pair correlations were higher for MZ than for DZ twins, although our test for significant genetic variance showed statistical significance only for intake of complex carbohydrates. We conclude that MZ twins share demographic and lifestyle factors that might influence the risk of IHD and blood lipid levels to a greater degree than do DZ twins, although it is difficult to say if these similarities in lifestyle result from genetic influences or not. Nevertheless, ascribing differences between correlations in MZ and DZ twin pairs for lipid levels as being purely “genetic”–as implicit in conventional measures of heritability–is likely to overestimate the influence of genetic factors.
Relationship of epithelial ovarian cancer to other malignancies within families
Authors: Schildkraut Joellen M. , Thompson W. Douglas , Vogler G. P. , Rao D. C. 
Published: June 2005

AbstractThe relationship of family history of cancer of the breast, colon/rectum, cervix, endometrium, lung, and thyroid to the risk of epithelial ovarian cancer was investigated in a large population‐based case‐control study. The data consisted of family histories from 493 epithelial ovarian cancer cases and 2,465 controls aged 20–54 years. After controlling for potential confounders, risk for epithelial ovarian cancer was found to be significantly elevated among women reporting breast cancer and colo/rectal cancer in a first‐degree relative. Adjusted odds ratios were 1.5 (95% CI = 1.1‐2.1) and 1.9 (95% CI = 1.1‐3.3), respectively. None of the remaining four types of cancer was found to be statistically associated with the risk of epithelial ovarian cancer. However, when histologic subtypes of epithelial ovarian cancer were considered, a family history of breast cancer was found to be associated with an elevated risk of endometrioid ovarian cancer (odds ratio = 2.3; 95% CI = 1.1‐4.7), as was a family history of endometrial cancer (odds ratio = 2.7; 95% CI = 1.0‐6.9). The results are considered in the context of other studies of familial patterns of cancer and are compared with published findings concerning the occurrence of multiple primary cancers in the same individual. The findings indicate that further study is warranted regarding possible genetic relationships between epithelial ovarian cancer and cancers arising in other organs.
Familial risk of cancer among randomly selected cancer probands
Authors: Sellers Thomas A. , Elston Robert C. , Stewart Cecily , Rothschild Henry , Vogler G. P. 
Published: June 2005

AbstractSeveral investigators have reported that relatives of lung cancer probands have a greater‐than‐normal likelihood for developing some form of cancer. To evaluate whether this familial risk is general for probands with cancer at any site or limited to lung cancer probands, we did a case‐control study in which probands having cancer affecting any body site were identified and their pedigree data were tabulated. Telephone interviews and a mailed questionnaire were used to obtain cancer histories and environmental exposures on the families of 41 lung cancer probands, 105 probands with cancer other than lung, and 127 spouse families. Cumulative tobacco exposure (P<.05), occupational hazards (P<.005), and age of the family relatives (P<.0001) were found to be statistically significant predictors of cancer risk. With consideration given for these variables, we determined that siblings of lung cancer probands were at slightly greater risk of cancer of any kind (odds ratio [OR] = 1.43, P = .06) than siblings in the control group. Much of the elevated risk was attributable to an excess of lung cancer (OR = 2.49, P = .06). Siblings of non‐lung/non‐breast cancer probands were also determined to be at increased risk of lung cancer as well (OR = 1.61, P = .06). For parents, the risk was lower, although parental information may have been underreported.
An expected decrease in the incidence of autosomal recessive disease due to decreasing consanguineous marriages
Authors: Saito Tomohiro , Vogler G. P. , Rao D. C. 
Published: June 2005

AbstractA recent decline in consanguineous marriages in Japan should have resulted in a decrease in the incidence of autosomal recessive disorders. Theoretical estimates were made of the chronological decrease in the incidence using a formula for Hardy‐Weinberg expectation in a partially inbred population and applying appropriate consanguinity rates, taken from the literature, during the period from 1942 to 1983. Theoretically estimated also, using Nei's extended Dahlberg's formula, is a chronological decrease in the proportion of first‐cousin marriages among the parents of affected individuals.The estimated decrease in both indices during the period was substantial, and greater in disorders of low gene frequencies. The incidence of major autosomal recessive disorders was estimated to have decreased by 40 to 80% during the period. The proportion of first‐cousin marriages among the parents of affected individuals dropped from 40–70% in 1945 to 5–15% in 1983.Theoretical estimates of the magnitude of the decrease in the incidence and in the proportion of first‐cousin marriages among the parents agreed fairly well with those of observed figures in phenylketonuria and Wilson's disease.
Circulatory disease mortality and diabetes incidence in 27 families with Friedreich ataxia
Authors: Morrell Daphne , Chase Charles L. , Swift Michael , Vogler G. P. , Rao D. C. 
Published: June 2005

AbstractFriedreich ataxia (FRA) is an autosomal recessive neuromuscular disorder in which nearly all affected homozygotes eventually develop significant cardiomy‐opathy and a substantial proportion also develop diabetes mellitus. Diabetes and early heart disease have been observed previously in close blood relatives of FRA patients. To test the hypothesis that FRA heterozygotes may have elevated rates of heart disease mortality and diabetes incidence, we compared the rates of these conditions in 1,191 adult blood relatives to those in 745 nonblood relative spouse controls in 27 families of FRA patients.We found no evidence for an excess of diabetes in the blood relatives. For three broad categories of circulatory disease mortality, the FRA blood relatives had significantly higher rates than the spouse controls. However, when each relative's prior probability of heterozygosity for the FRA gene was taken into account, the resulting estimates of relative risk of dying from circulatory disease for FRA heterozygotes compared to nonheterozygotes were not significantly elevated. Since the latter analysis provides the best test of the hypothesis, our data did not strongly support the hypothesis that FRA heterozygotes are at increased risk of cardiac death.