bluuebunny/crossref_metadata_2025_split huggingface dataset:
An approach to the multivariate analysis of high‐density‐lipoprotein cholesterol in a large kindred: The Bogalusa Heart Study
Authors: Amos C. I. , Wilson A. F. , Rosenbaum P. A. , Srinivasan S. R. , Webber L. S. , Elston R. C. , Berenson G. S. , Rao D. C. 
Published: June 2005

AbstractThe genetic determination of high‐density‐lipoprotein cholesterol (HDL‐C) levels was evaluated using segregation analysis techniques in a large multigenerational kindred with a high prevalence of coronary heart disease and myocardial infarction. Univariate segregation analysis of HDL‐C levels with the effects of age and sex removed by regression provided evidence of a Mendelian mode of inheritance for a portion of the variability in HDL‐C levels. Subsequent analyses included low‐density‐lipoprotein cholesterol (LDL‐C) levels and several behavioral and anthropometric variables that affect HDL‐C levels. Pedigree discriminant analysis was used to find the linear functions of the variables that maximized the likelihood given the pedigree structure and assuming monogenic segregation. The best linear function was found to be approximately equivalent to the log of the HDL‐C to LDL‐C ratio, with concomitant and environmental effects removed by regression. Genetic hypotheses were tested by cross‐validation; linear functions derived from data on each side of the kindred were used to test hypotheses on the other side of the kindred. On one side of the kindred, all hypotheses were accepted. On the other side of the kindred, only Mendelian inheritance of the linear function was indicated. Segregation of the age‐ and sex‐adjusted HDL‐C values, and of the linear function, was evaluated using a regressive model that allows for intrafamilial correlations in addition to a monogenic effect. All analyses provide evidence for levels of HDL‐C being controlled by a major locus with neither dominant nor recessive expression.
Two‐disease locus model: Sib pair method using information on both HLA and Gm
Authors: Dizier M. Hélène , Clerget‐Darpoux Françoise , Rao D. C. 
Published: June 2005

AbstractAn adaptation of the sib pair method is given for testing the independence of transmission of Gm and the disease, using variable X (which gives information on the phenotypic identity of a sib pair for Gm). Then the joint distribution of IBD for HLA and X for Gm among affected sib pairs was derived under different two‐locus models (multiplicative and other) in which one locus is strictly linked to HLA and the other to Gm. We also propose a test for a joint effect of HLA and Gm and whether this effect is multiplicative or not.
Prevalence and associations of apolipoprotein A‐I linked DNA polymorphisms: Results from a population study
Authors: Anderson Richard A. , Benda Thomas J. , Wallace Robert B. , Eliason Steven L. , Lee Julia , Burns Trudy L. , Rao D. C. 
Published: June 2005

AbstractSubjects from a geographically defined population were screened for restriction fragment length polymorphisms linked to the apolipoprotein A‐I (apoaA‐I) gene locus. The polymorphic DNA fragments detected with an apoA‐I cDNA probe after digestion with the restriction endonucleases Sac I (S1 and S2 alleles), Msp I (M1 and M2 alleles), or Pst I (P1 and P2 alleles) were used to define polymorphic haplotypes. The uncommon S2M1 haplotype was present in the leukocyte genomic DNAs of 6 of 22 (27%) subjects with high‐density lipoprotein cholesterol (HDL‐C) levels in the lowest decile, in contrast to none of the 20 subjects with HDL‐C levels in the highest decile. With repeat determinations of the HDL‐C levels 10 years later, the levels of the subjects in the low decile group with the S1M1 haplotype had regressed toward the population mean, while the regression was much less substantial for the S2M1 group. The mean triglyceride (TG) level in low HDL‐C subjects with the S2M1 haplotype was also higher than in those without it (295 vs 246 mg/dl), although not all of those with the S2M1 pattern were hypertriglyceridemic. The prevalence of the P2 allele was increased in a series of men with angiographically confirmed premature coronary artery disease (CAD) (P2 present in 7 of 43) as compared to a group of age‐matched controls without CAD (1 of 36). There was no difference between these groups in the prevalence of the S2 allele. These results suggest that a particular pattern of apoA‐I linked genetic polymorphisms is associated with lower HDL‐C levels. This type of analysis will be useful in studies of the epidemiology of abnormal lipid states and may eventually provide a genetic marker to identify those at risk for early coronary artery disease (CAD) so that focused hygienic interventions can be effectively instituted.
Causes of death in huntington disease as reported on death certificates
Authors: Haines J. L. , Conneally P. M. , Rao D. C. 
Published: June 2005

AbstractHuntington disease (HD) is a late onset autosomal dominant neurological disorder. Two hundred fifty‐three death certificates of HD‐affected individuals from four midwestern states were examined to determine the completeness of reporting HD on the death certificates. Overall, 66% of death certificates indicated HD as a primary or contributory cause of of death. There was significantly better reporting on more recent death certificates, but even since 1979, 16% did not report HD. The implications to those researching HD family histories and to the accuracy of mortality rates are discussed.
Relationship of prevalence of non‐insulin‐dependent diabetes mellitus to Amerindian admixture in the Mexican Americans of San Antonio, Texas
Authors: Chakraborty Ranajit , Ferrell Robert E. , Stern Michael P. , Haffner Steven M. , Hazuda Helen P. , Rosenthal Marc , Rao D. C. 
Published: June 2005

AbstractA genetic and epidemiological survey of non‐insulin‐dependent diabetes mellitus (NIDDM) was conducted among the Mexican Americans residing in three socio‐economically distinct areas of San Antonio, Texas: a low socioeconomic (SES) traditional area (barrio), a middle SES, ethnically balanced area (transitional), and a high SES, predominantly Anglo area (suburb). Seventeen polymorphic markers were used to relate the prevalences of NIDDM with the extent of Amerindian ancestry of 1,237 Mexican Americans of these three residential areas. While only the RH and haptoglobin loci showed evidence of association with NIDDM, an admixture analysis of the combined allele frequency data revealed a pattern of decreasing NIDDM prevalence with increasing socioeconomic status (as approximated by neighborhood of residence) and a parallel decrease in Amerindian ancestry. The rank‐order correlation between NIDDM prevalence and Amerindian admixture is 0.943 (P < .001) for the crude prevalence rate and 0.829 (P < .02) for the age‐adjusted rate. Nested gene diversity analysis revealed that the heterogeneity of allele frequencies is more pronounced when individuals were classified by their NIDDM disease status as compared to the classification by neighborhood. Estimation of Amerindian ancestry of each individual did not reveal any significant change in the shape of the distributions of individual admixture proportions in diabetics as compared to the controls. Nevertheless, the results suggest that genetic factors partially explain the differences in NIDDM prevalence observed between the Mexican American and Anglo populations in the southwestern United States.
Congenital anomalies in American Indians of British Columbia
Authors: Lowry R. B. , Thunem N. Y. , Silver M. , Rao D. C. 
Published: June 2005

AbstractBirth prevalences of congenital anomalies in the American Indians of British Columbia are compared with those of the total British Columbia population. This study is based on data from the British Columbia Health Surveillance Registry for a 16‐year period (1966–1981) judged to be the most reliable reporting period in the 35‐year history of the registry. The overall congenital anomaly frequency is lower in Indians than in the general population (45 versus 60 per 1,000 livebirths). The Indian rates for individual anomalies are lower than the corresponding general population rates with the exception of orofacial clefting and congenital heart defects. Defects of the central nervous system in both populations are comparable. There is a striking paucity of hypospadias, other anomalies of the genital organs and foot deformities in Indian males. It is suggested that the differences in the congenital anomaly rates between the American Indians and the non‐Indians of British Columbia may reflect genetic differences between the two groups, but differences in ascertainment and infant mortality probably also play a role.
Familial predisposition for otitis media in Apache Indians at Canyon Day, Arizona
Authors: Todd N. Wendell , Rao D. C. , Cloninger C. Robert 
Published: June 2005

AbstractThe familial occurrence of otitis media was studied in White Mountain Apache Indians at Canyon Day, Arizona. Of the 760 residents, 366 persons were seen during a village survey for otitis media. There were 133 first‐degree relatives involving 113 first‐degree relative pairs. Of these, there were 38 children involving 19 separate sibling pairs, for whom age‐ and sex‐matched controls could be assigned. Tympanic membrane scarring was assumed to be a marker of prior otitis media. The findings suggested (P < .01 for the nonindependent first‐degree relative pairs, and P < .05 for the independent sibling pairs) a familial predisposition. With the additional assumption that the severity of tympanic membrane scarring can be ranked, no association of severity of otitis media was apparent in the first‐degree relatives.
Testing the association between polymorphic markers and quantitative traits in pedigrees
Authors: George Varghese T. , Elston Robert C. , Rao D. C. 
Published: June 2005

AbstractA statistical model that uses an iterative maximum likelihood estimation procedure is proposed for measuring and testing the association between polymorhphic genetic markers and quantitative traits in human pedigrees, after adjusting for covariates such as age and sex. The model allows the quantitative trait to have a familial correlation structure among the individuals in the sample and to follow one of a broad class of skewed or kurtotic underlying distributions. The use of the model is illustrated, and the results are compared to those using models that assume normality without any transformation and do not incorporate familial correlations.
Robust inference for variance components models in families ascertained through probands: I. Conditioning on proband's phenotype
Authors: Beaty T. H. , Liang K. Y. , Rao D. C. 
Published: June 2005

AbstractA robust approach for estimating standard errors of variance components by using quantitative phenotypes from families ascertained through a proband with an extreme phenotypic value is presented. Estimators that use the multivariate normal distribution as a “working likelihood” are obtained by computing conditional In‐likelihoods, conditional first and second derivatives in a Newton‐Raphson approach. Robust estimates of standard errors about the estimators are also provided. Tests of hypotheses are based on a modification of the score test, which allows the assumption of multivariate normality to be relaxed. Conditional goodness‐of‐fit statistics are proposed that can be used to examine the fit of separate pedigrees to the overall model. This robust approach for estimating the standard errors for variance components by conditioning on the proband's phenotype will allow general inferences to be made from the analysis of families ascertained through probands with extreme or unusual phenotypes and should be most appropriate for studying many physiological traits that may be intrinsically nonnormal.
Nonrandom segregation: Uniformly most powerful test and related considerations
Authors: Majumder Partha P. , Pal Nabendu , Rao D. C. 
Published: June 2005

AbstractWhen nonrandom segregation of marker haplotypes from parents to offspring is detected, leading to an increased parental haplotype sharing by affected offspring, an association between the disease and the marker loci is often inferred. In this paper, we provide the uniformly most powerful test for testing nonrandom segregation, and compare the power of this test with another test that is available in the literature. Other statistical properties of the two tests are also discussed. Further, since nonrandom segregation can result from linkage of the disease and marker loci, when the hypothesis of random segregation is rejected, it is of interest to estimate the underlying parameter assuming linkage. We provide an estimation procedure.
A genetic analysis of clubfoot in Hawaii
Authors: Yang Huiying , Chung Chin S. , Nemechek Robert W. , Rao D. C. 
Published: June 2005

AbstractThe roles of major genes and multifactorial inheritance in the etiology of clubfoot (talipes equinovarus) were investigated based on 365 nuclear families consisting of three major racial groups of Hawaiians, Caucasians, and Orientals in Hawaii. Complex segregation analysis was employed using the mixed model with four parameters: major gene displacement (t), degree of dominance (d), gene frequency (q), and heritability (H). Heterogeneity was evident among the racial groups in the pattern of segregation of clubfoot. The most plausible genetic model is the presence of major gene effects with the multifactorial component for the Hawaiian and Caucasian groups, whereas no major gene action is evident for the Oriental group.
Plasma cholesterol variation in the national heart, lung and blood institute twin study
Authors: Christian Joe C. , Borhani N. O. , Castelli W. P. , Fabsitz R. , Norton J. A. , Reed T. , Rosenman R. , Wood P. D. , Yu P. L. , Rao D. C. , Borecki I. B. 
Published: June 2005

AbstractPlasma cholesterol was measured in the fifth decade of the life of 249 pairs of monozygotic (MZ) and 262 pairs of dizygotic (DZ) World War II veteran twins and 70% of the same cohort 10 years later. There were no significant differences between the mean cholesterol values for MZ and DZ twins, and the within DZ pair mean squares were significantly larger than the within MZ pair mean squares for all of the cholesterol variables measured. However, the DZ twins were found to have greater total variance, positive skewness, and leptokurtosis than the MZ twins for total and high‐density lipoprotein cholesterol, and the total/high‐density ratio. Comparisons with published data revealed that the variance of DZ twins was similar to that of singletons while the MZ twins have smaller total variance, perhaps owing to a missing component of variation. Hypotheses for the source of the differences in the zygosity distributions are proposed including environmental influences (pre‐ or post‐natal and within‐ or among‐families), genetic differences, and selection at the time of induction into the armed services. Because of the differences in total variance of the two zygosities it is difficult to know which estimates of genetic variance or heritability have the least bias. However, these data provide clues that may lead to further understanding of sources of plasma cholesterol variation that could be important to the future understanding of risk for coronary heart disease.
A major simplification in the preliminary ordering of linked loci
Authors: Wilson Susan R. , Rao D. C. 
Published: June 2005

AbstractFor ordering n loci there are n!/2 distinct orders to be evaluated. Each order has a different set of event probabilities where the events are the occurrence and nonoccurrence of recombination in each interval determined by that order. To choose between the distinct orders, further assumptions are necessary. The biologically natural one is that the recombination rate over a subinterval is always less than or equal to the recombination rate over the larger interval. A second assumption is necessary, and the one commonly made is that there is no interference. Using a simple matrix approach it is shown that a consequence of these assumptions is that the optimal order is the order with the minimum value of the product of the adjoining pairwise recombination rates. This result gives a very simple procedure for obtaining preliminary genetic maps that may be used as starting points for more computer‐intensive, maximum‐likelihood, multipoint techniques.
Heritability estimate for refractive errors—a population‐based sample of adult twins
Authors: Teikari Jaakko M. , Kaprio Jaakko , Koskenvuo Markku K. , Vannas Antti , Rao D. C. 
Published: June 2005

AbstractThe population‐based Finnish Twin Cohort study was used to establish a heritability estimate for refractive errors especially for myopia. The twin cohort was derived from adult same‐sexed twins in Finland. The total number of twins with both members alive in 1984 was 23,570. Of these, 3,676 twin pairs were monozygotic, and 8,109 pairs dizygotic. The sample for the present study was linked from the Finnish Police Force data base in 1984, where information of a person's possession of a driver's license and the obligation to wear glasses for far correction when driving a motor vehicle is recorded. Correlations in liability were estimated according to a multifactorial method of Smith. Falconer's heritability was 0.62 among males and 0.98 among females in the age group 28–29 years. When compared to previous twin studies of myopia, the proband concordance rates were higher for both MZ and DZ twin pairs.
A nationwide evaluation of multiple congenital abnormalities in Hungary
Authors: Czeizel A. , Kovács Márta , Kiss P. , Méhes K. , Szabo L. , Oláh Éva , Kosztolányi G. , Szemere G. , Kovács Helga , Fekete G. , Neel James. V. 
Published: June 2005

AbstractA population‐based study of 7,049 index patients with multiple congenital abnormalities (MCA) born in Hungary during 1973–1982 was organized by the Hungarian Center for Congenital Anomaly Control. All clinically recognized syndromes and associations which were submitted (2,049) were accepted without any further follow‐up. New or supplementary information was requested in the case of unspecified MCA (320). A copy of detailed necropsy records was requested from pathologists in lethal cases (2,022). Following these steps, apparent but not true instances of MCA were excluded (399), and an attempt was made to assign as many of the remainder as possible in 17 well‐delineated MCA entities (900). The living index patients with severe MCA were referred where possible to the regional centers for evaluation (864). One hundred and seventy entities were identified, and seven cases were excluded as not representing MCA. In the so‐called 3,393 unidentified cases for which no diagnosis was possible, the component abnormalities were tabulated according to their number. The final count was 6,643 cases with MCA, which is equivalent to a birth prevalence of 4.0 per 1,000 total births, and to 10% of recorded cases with congenital anomalies. As a result of this program the proportion of recognized syndromes and associations among children with MCA increased from 29% to 47%. The accuracy of diagnoses has improved, e.g., the occurrence of unspecified cases decreased from 4.5% to 2%.
Genetic analysis of human breast cancer: Implications for family study designs
Authors: Andrieu Nadine , Demenais Florence , Martinez Maria , Rao D. C. 
Published: June 2005

AbstractGenetic analysis of human breast cancer, as with many common diseases, raises several problems including sampling strategies, genetic heterogeneity, and geneenvironment interactions. A reanalysis of 200 Danish breast cancer pedigrees, under the unified mixed model, was conducted to investigate more specifically these three points. We found that use of different sampling schemes leads to similar conclusions: familial transmission of breast cancer in this whole Danish sample cannot be accounted for by the Mendelian segregation of a dominant gene. Homogeneity tests, based on an a priori subdivision of the sample, were all nonsignificant under a given genetic model. However, it was possible to isolate a particular subgroup of pedigrees displaying only breast cancer, which was compatible with the segregation of a dominant gene. We have also shown that correct specification of a liability indicator according to epidemiological factors is of major importance to detect a major effect under the mixed model. Our results emphasize the need to design family studies including various types of information in the probands and family members to permit some progress in the understanding of complex diseases.
HLA and down syndrome (DS): Parents at the origin of the nondisjunction share no more HLA‐A and ‐B antigens with their DS child than controls
Authors: Stoll C. , Alembik Y. , Armbruster N. , Tongio MM , Mayer S. , Rao D. C. 
Published: June 2005

AbstractFifty couples and their children with Down syndrome (D.S.) were typed for HLA‐A and HLA‐B antigens and compared to 50 control families and 464 blood donors. The parental origin of the extra chromosome 21 was determined by cytogenetic methods. All individuals were caucasians and there was no history of consanguinity. No excessive HLA sharing was present in D.S. parents. The mothers of D.S. shared no more HLA antigens with their D.S. children than the control mothers with their normal children (14% vs. 18%). Thirteen of the fifty pairs (26%) (parent in whom the nondisjunction occurred and D.S. child) shared three HLA antigens at the A and/or B locus. This was not significantly higher than the proportion in the control group (12/50 or 24%). These data suggest that it is not the sharing of HLA‐A and HLA‐B antigens between the parents or between the parent who was the origin of the nondisjunction and the D.S. child that is related either to the occurrence of trisomy 21 zygotes or to prenatal survival of affected embryos and fetuses.
Some effects of selection strategies on linkage analysis
Authors: Cox Nancy J. , Hodge Susan E. , Marazita Mary L. , Spence M. Anne , Kidd Kenneth K. , Rao D. C. 
Published: June 2005

AbstractA study was designed to address the relative merits of different sampling strategies for detecting linkage. Genotypes of pedigree members were generated by the use of a single genetic model, and the pedigrees were subdivided into dominant‐appearing, recessive‐appearing, and “interesting” subsets. An investigator blind to how the data had been generated applied two different selection rules to determine which individuals in each pedigree would be “typed” for linkage analysis. Linkage analyses were then conducted on these pedigree subsets, as well as on the combined data, by the use of three autosomal dominant models, three autosomal recessive models, and the generating (i.e., “true”) model. Results suggest (1) that linkage is likely to be detected even in the absence of knowledge of the mode of transmission, if a range of models can be examined; (2) that false evidence for heterogeneity will not necessarily result when pedigrees are selected according to apparent mode of transmission for analysis; (3) that recessive‐appearing pedigrees (i.e., those with multiplex sibships) may be particularly useful for detecting linkage; and (4) that including information on unaffected second‐degree relatives adds little to linkage studies of affected individuals and their first‐degree relatives.