bluuebunny/crossref_metadata_2025 huggingface dataset:
Do female rhesus macaques choose novel males?
Authors: Manson Joseph H.
Published: June 2005

Prior research has shown that estrous female rhesus macaques (Macaca mulatto) maintain spatial proximity preferentially to lower‐ranking males. In this paper, 657 h of focal individual follows of 48 free‐ranging estrous female rhesus macaques of two social groups during two mating seasons are used to evaluate the hypothesis that this phenomenon is attributable to female mate choice for novel males. This hypothesis is plausible because of the positive correlation between dominance rank and the length of time since a male immigrated into a group or matured in his natal group (i.e., his breeding tenure). However, partial correlation analysis showed that after removing the effect of dominance rank, there was no significant tendency for estrous females to maintain proximity preferentially to males of shorter breeding tenure. In contrast, removing the effect of breeding tenure did not eliminate the result that estrous females maintained proximity preferentially to lower ranking males. Novel (i.e., extra‐group, new immigrant, and newly matured natal) males did not consistently experience more estrous female proximity maintenance than non‐novel males, although sample sizes are too small to conclusively falsify this hypothesis. Within male‐estrous female dyads, responsibility for proximity maintenance did not tend to shift from the female to the male between consecutive mating seasons. Male breeding tenure was not significantly correlated with year‐to‐year change in responsibility for proximity maintenance. Male breeding tenure was not consistently correlated with female sexual refusal. In one of two social groups, in one of two mating seasons, females appeared to choose novel males. These data provide, at most, weak support for the hypothesis that female primates in multi‐male groups exercise mate choice for novel males. © 1995 Wiley‐Liss, Inc.
Heterochromatin and cytogenetic polymorphisms in Cebus apella (Cebidae, Platyrrhini)
Authors: Ponsà M. , García M. , Borell A. , Garcia F. , Egozcue J. , Gorostiaga M. A. , Delprat A. , Mudry M.
Published: June 2005

Cytogenetic studies have been carried out in 39 specimens of C. apella of different origins. Three different morphologies, one affecting the long arm of chromosome 4 and two affecting pair 17, have been detected. In each case, they can be related by paracentric inversions. Heterochromatin polymorphisms affecting terminal or interstitial C+ regions have also been observed. The length of the terminal heterochromatic region in the long arms of chromosome 11 is variable in C. apella sp., in C. a. paraguayanus and absent in the C. a. nigritus specimens studied. Interstitial C + bands can be observed in the long arms of the biarmed chromosomes 4 and 6, and in the long arms of the acrocentric pairs 12, 13, 17, 18, 19, 20, and 21. Interstitial C + bands in the long arms of chromosomes 4, 12, 17, and 19 are present in all animals studied, although their size is variable, especially in the case of chromosomes 17 and 19. © 1995 Wiley‐Liss, Inc.
Developmental perspective on size change and allometry in evolution
Authors: Shea Brian T.
Published: June 2005

The evolution of changes in body size is one of the most important patterns in the history of life. Its importance arises from both the frequency of the pattern and the biological implications of size change itself, which affects myriad aspects of an organism's structure and function through well‐known scaling relationships. Yet relatively little attention has been focused on the underlying genetic and developmental controls of size change or their implications with regard to other morphological changes. Here, I review the endocrine growth axis and show that variation in several key growth‐control substances, particularly growth hormone (GH) and insulin‐like growth factor I (IGF I), is clearly linked to intraspecific differences in postnatal growth rates and terminal body size. I intentionally review a considerable amount of literature on nonprimate mammals because this research is vital to an understanding of the general topic. Research on human pygmies, giant transgenic mice, and other models of growth disturbances indicates that shifts in GH and/or IGF I levels not only yield the expected changes in terminal body size, but also result in simple truncations or extensions of underlying allometric patterns. These data provide a possible developmental basis for the common finding of ontogenetic scaling and coordinated transformations in series of closely related fossil or living species that differ in body size. At present, however, this must be viewed as a hypothesis that requires testing through interspecific analyses. A consideration of previous interpretations of the morphological distinctions of human pygmies and some other organisms demonstrates the novel information that a developmental perspective brings to morphological comparisons. Clearly, knowledge of the genetic and developmental controls of morphogenesis will greatly enhance our understanding of a multitude of evolutionary patterns, processes and mechanisms, for it is perturbations in these these controls that ultimately produce the raw material for evolutionary transformations.
The evolution of primate communities and societies in Madagascar
Authors: Kappeler Peter M. , Ganzhorn Jörg U.
Published: June 2005

During their 120 to 165 million years of isolation, the flora and fauna of Madagascar evolved, to a large extent, independently of the African mainland.1 In contrast to other oceanic islands, Madagascar is large enough to house the major components of tropical ecosystems, allowing tests of evolutionary hypotheses on the level of complete communities. Taking lemurs, the primates of Madagascar, as an example, evolutionary hypotheses correctly predict the organization of their community structure with respect to ecological correlates. Lemur social systems and their morphological correlates, on the other hand, deviate in some respects from those of other primates. Apparently, lemur social systems are influenced by several selection pressures that are weak or rare in other primates. These include variable activity patterns and avoidance of infanticide. The interspecific variation in lemur social systems therefore offers a unique opportunity for a comprehensive study of the determinants of primate social systems.
Predation on primates: Ecological patterns and evolutionary consequences
Authors: Isbell Lynne A.
Published: June 2005

It has long been thought that predation has had important ecological and evolutionary effects on primates as prey. Predation has been theorized to have been a major selective force in the evolution of hominids.1In modern primates, behaviors such as active defense, concealment, vigilance, flight, and alarm calls have been attributed to the selective pressures of predation, as has group living itself. It is clear that primates, like other animals, have evolved ways to minimize their risk of predation. However, the extent to which they have been able to do so, given other constraints of living such as their own need to acquire food, has not yet been resolved. Perhaps most hotly debated is whether predation has been the primary selective force favoring the evolution of group living in primates. Part of the difficulty in resolving the debate lies in a paucity of direct evidence of predation. This is regrettable yet understandable since primatologists, by definition, focus on the study of primates, not predators of primates (unless these are also primates). Systematic direct evidence of the effects of predation can best be obtained by studying predators that are as habituated to observers as are their primate prey. Until this is done, we must continue to rely on opportunistic accounts of predation and predation attempts, and on systematically obtained indirect evidence. Such data reveal several interesting patterns: (1) although smaller primates may have greater predation rates than larger primates, even the largest primates are not invulnerable to predation; (2) the use by primates of unfamiliar areas can result in higher predation rates, which might be one pressure favoring philopatry, or site fidelity; (3) arboreal primates are at greater risk of predation when they are more exposed (at forest edges and tops of canopies) than in more concealed locations; (4) predation by mammalian carnivores may often be episodic; and (5) terrestrial primates may not experience greater predation than arboreal primates.
Rethinking genes
Authors: Marks Jonathan , Lyles R. Brent
Published: June 2005

The gene is the central construct of twentieth‐century biology and evolution. It is a construct because, like “culture” in anthropology, “gene” is widely used and is central to the discipline's discourse, but eludes rigorous definition. Although the gene is acknowledged as a material entity, its membership criteria are unclear and its boundaries are fuzzy—indeed, more than one can occupy the same space at the same time. The purpose of this essay is to bring to light recent refinements in our conception of the gene and their implications for its use in biological anthropology.
Skeletal biology and behavior in ancient humans
Authors: Bridges Patricia S.
Published: June 2005

For many years, it has been known that archaic hominids had more robust long bones than do living populations, a fact that has been linked to their more physically strenuous lives. But many questions remain. How much stronger, for example, were Neanderthals than living humans? And what does this difference in strength tell us about the behavior of our ancestors?

Recent research has shown that some of our earlier assumptions about robusticity and behavior in earlier humans are either simplistic or untrue. For example, it is now clear that although earlier humans were, on the average, stronger than living peoples, this is not invariably the case. Some modern human groups have even stronger humeri than those of Neanderthals. The fact that changes in robusticity do not always neatly coincide with subsistence or technological change suggests that interpretations derived in large measure from stone‐tool technology and other artifactual evidence may be misleading. This new information on physical strength in earlier humans necessitates a reassessment of traditional ideas about earlier human behavior.
Historical perspectives on human‐assisted biological invasions
Authors: Burney David A.
Published: June 2005

Of all the things we have done to the Earth so far, which one is likely to make the most indelible mark? I have been posing this question to students and colleagues for some time, and usually receive one of three reasonable replies: habitat destruction, human overpopulation, or global climate change. Yet as bad as all these maladies are, they are, to some extent, reversible on time scales to which we can relate. The remedies for these problems, despite mammoth cultural and economic obstacles, can be visualized generally in terms of technology and scientific theory. Only the will is lacking. On longer geological and evolutionary time scales, most such human impacts, if corrected soon, would be mere blips, perturbations of the ecosphere that would leave only a few detectable traces in the fossil record a million years hence.
An application of a model for a genotype‐dependent relationship between a concomitant (age) and a quantitative trait(LDL cholesterol)in pedigree data
Authors: Moll Patricia P. , Sing Charles F. , Lussier‐Cacan Suzanne , Davignon Jean , Rao D. C.
Published: June 2005

In most genetic studies in humans the variability in a quantitative trait is adjusted for variability in concomitants (age, sex, etc) using a single regression equation prior to analyses of pedigree data. To illustrate an alternative approach, a single locus genetic model was tested. This model incorporates genotypic effects on the level of the trait, the variability in the trait, and the relationship between a concomitant and the trait. In this study, the model was applied to measures of age and low‐density lipoprotein (LDL) cholesterol in a large kindred with familial hypercholesterolemia. The application of this model to 322 individuals in four generations provided evidence that genotypic variation at a single locus influences LDL levels early in life, the rate of increase of LDL with age and the phenotypic variance. A model with genotype‐dependent slope and variance fit the data signifcantly better than a model with slope and variance independent of genotype. The inclusion of age‐specific genotypic differences contributed to identification of high‐risk individuals, to statistical support for a major locus, and to evidence for genetic determination of the tracking of LDL levels. Models that incorporate genotype‐specific concomitant effects have the potential to represent more realiscally the relationship between genotypic variability and quantitative phenotypic variation than models that assume that these effects do not exist.
Glucose tolerance and ancestral genetic admixture in six semitraditional pacific populations
Authors: King H. , Zimmet P. , Bennett P. , Taylor R. , Raper L. R. , Rao D. C.
Published: June 2005

Population‐based data on 1,842 subjects from six semitraditional Pacific communities, collected in the years 1978–1983, have been compared in order to examine the hypotheses that differences in the distribution of plasma glucose concentration between populations are to some extent genetically determined, and that non‐Austronesian (NAN) Melanesians are relatively resistant to glucose intolerance. Semitraditional communities were chosen for study so that the comparison would be minimally confounded by either known or as yet undetermined environmental factors associated with nontraditional living, the effects of which may vary between populations. The samples were also selected so as to provide a gradient of proportional NAN and AN admixture. They were drawn from the following regions: the highlands of Papua New Guinea, New Caledonia, Fiji, the Wallis Islands, Western Samoa, and Kiribati (formerly the Gilbert Islands). The Papua New Guinea highlanders, of entirely NAN ancestry, were regarded as the baseline population.

A gradient of increasing mean 2‐hr plasma glucose concentration was observed across the six populations and differences persisted between populations, after controlling for age and obesity. Variations in diet, physical activity, and degree of sociocultural modernization were not considered a sufficient or consistent explanation of these findings and they therefore lend tentative support to the hypothesis of a genetic component to variability in glucose tolerance.

The relationship between population estimates of glucose tolerance and estimates of the genetic distance from the baseline NAN Melanesian sample was examined. With the notable exception of Fiji, there was evidence of a linear correlation between the two parameters.
Interpretation of LOD scores with a set of marker loci
Authors: Thompson E. A. , Nance Walter E.
Published: June 2005

The problem discussed is that of interpreting LOD scores when multiple markers are tested for linkage with a particular disease locus. Provided the tests are based on independent segregations, both the maximum and the average LOD can be translated into a score that would have the same significance level were it the result of a single test.
Genetic and environmental causes of variation in renal tubular handling of sodium and potassium: A twin study
Authors: Whitfield J. B. , Martin N. G. , Rao D. C.
Published: June 2005

We have conducted a study of renal sodium and potassium reabsorption in 205 pairs of twins on freely chosen diets; 89 of the subjects were studied on more than one occasion. Renal tubular sodium and potassium handling, as measured by the fractional excretions FENa and FEK, show repeatable differences between individuals.

Siblings (in this case monozygotic and dizygotic pairs of twins) are more alike in this respect than unrelated individuals. Comparison of monozygotic and dizygotic twin pairs indicates that genetic, rather than shared environmental, factors are probably responsible for this similarity, with heritability estimates of 0.5 for sodium and 0.6 for potassium. There are indications of sex differences in the sizes of the genetic and environmental effects for both variables and indications that the genetic effects may be qualitatively different for FEK. Such findings need further investigation.
Multivariate path analysis of familial resemblance
Authors: Vogler George P. , Cockerham C. C.
Published: June 2005

A method is presented for applying path analysis to general multivariate models of familial resemblance. In path models formulated using this approach, variables are defined as column vectors, path coefficients are defined as matrices of path coefficients, and correlations are defined as matrices of correlations. By applying a few simple rules for multivariate path analysis, general multivariate expected correlations can be derived from a path diagram which is essentially as simple as a univariate diagram and which can be used to analyze any number of variables. Multivariate expected correlations for three models of familial resemblance are derived, with particular attention given to the modeling of assortative mating: nuclear families with a phenotypic homogamy model of assortative mating, nuclear families with a social homogamy model of assortative mating, and twins and their parents with phenotypic homogamy. These models are applicable to many of the types of studies commonly undertaken in genetic epidemiology. The simplicity of the technique facilitates analyses of the etiology of variation and covariation among variables measured in such studies.
Studies on vitiligo I. Epidemiological profile in Calcutta, India
Authors: Das S. K. , Majumder Partha P. , Chakrabotry Ranajit , Majumdar T. K. , Haldar B. , Rao D. C.
Published: June 2005

An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5‐fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.
A chi‐square test to distinguish allelic association from other causes of phenotypic association between two loci
Authors: Ott Jurg , Rao D. C.
Published: June 2005

In unrelated individuals, their phenotypes at two gene loci may appear correlated. The two major reasons for such a deviation from independence are linkage disequilibrium (allelic association) and an interaction between the phenotypes. In this paper, it is shown how the usual chi‐square test for association of phenotypes can be partitioned into two components, one being due to allelic association and the other being due to other causes of phenotypic association. The test is demonstrated with an example.
Genetic analysis workshop III: Sib pair analyses to determine linkage groups and to order loci
Authors: Elston R. C. , Keats B. J. B.
Published: June 2005

The methods proposed by Haseman and Elston [1972] were used to estimate the proportion of genes identical by descent shared by each sib pair at each locus. These estimates were then used as a basis for obtaining all possible locus‐locus correlations. The 12 significant correlations (P < .01) and their rank order indicated the correct linkage groups and the order of the loci.
Genetic analysis workshop III: A biological model
Authors: Fain P. R. , Goldgar D. E.
Published: June 2005

A model for gene mapping that incorporates the concept of a limited crossover distribution is presented and applied to data simulated for GAW III.
Estimation of myriad haplotype frequencies
Authors: Maclean Charles J. , Morton Newton E. , Rao D. C.
Published: June 2005

The present paper demonstrates algorithms for applying gene counting estimation of haplotype frequencies in very large genetic systems. A factor union representation of phenotypes is used which conveniently yields the sets of potential haplotypes and diplotypes for each phenotype. Methods for storing and rapidly retrieving the relevant haplotypes are given. An example with several hundred frequencies is given which required a few seconds computing time for each estimation iteration on a small computer.

A computer program employing the methods described has been written in Fortran‐77 and is available to any investigator on request.
Demonstration of a common major gene with pleiotropic effects on immunoglobulin E levels and allergy
Authors: Borecki I. B. , Rao D. C. , Lalouel J. M. , McGue M. , Gerrard J. W. , Conneally P. M.
Published: June 2005

Atopic disease is generally recognized to be familial, although specific genetic components have yet to be identified. High levels of a unique class of immunoglobulins, immunoglobulin E (IgE), have been shown to be associated with allergies. Several investigators have reported evidence indicating a recessive regulatory locus where an individual with the homozygous recessive genotype has persistently elevated levels of IgE. Willcox and Marsh [1978] have proposed a hypothesis relating IgE production and liability to become allergic. A test of this hypothesis was carried out in the present study. Bivariate segregation analysis of IgE levels and allergy was performed on 173 nuclear families, and the results indicate that an IgE regulatory locus contributes to the familial transmission of allergy. The results are further discussed in the context of the Willcox and Marsh hypothesis.
A new model for the resolution of cultural and biological inheritance in the presence of temporal trends: Application to systolic blood pressure
Authors: Province M. A. , Rao D. C. , MacCluer J. W.
Published: June 2005

A contemporary path model for the resolution of cultural and biological inheritance is extended to incorporate temporal variation in family resemblance. Specifically, the genetic and environmental effects, like all other parameters of the model, are allowed to vary over an individual's age according to some specific mathematical functions. In the computer program BETREND a library of such functions is incorporated. Data on systolic blood pressure in 542 Japanese‐American nuclear families were analyzed. This new methodology detected significant temporal variation in cultural inheritance, a result that was not found previously by using static models which could only distinguish between adult and childhood heritabilities. Cultural heritability, estimated to be 10% at birth, increases to a maximum of 28% at age 36, at which time it declines until it eventually reaches 10% at age 49. Although not statistically significant, there was some evidence for temporal trends in genetic heritability as well. Ignoring trends, the genetic heritability was estimated as .30. On the other hand, trends in sibling environment were clearly nonsignificant. This model provides an objective method of testing the significance of temporal trends in familial resemblance by using multifactorial models, of resolving varying gene expression and transient environmental effects as possible sources of generating the observed temporal variation, and of estimating continuous changes in heritability with age.
Cancer and autoimmune disease in families with common variable immune deficiency
Authors: Morrell Daphne , Chase Charles L. , Swift Michael , Rao D. C.
Published: June 2005

Twenty‐five families including 34 individuals with common variable immune deficiency (CVID), with at least one affected female in each family, were studied. The distribution of cases within families was compatible with autosomal recessive inheritance, making it plausible to test hypotheses about the disease risk of heterozygote carriers of putative CVID genes by comparing the frequency of spouse controls. For cancer, observed numbers of cases or deaths were also compared to expected numbers derived from population rates.

No single family had an unusual clustering of autoimmune conditions, and, overall, autoimmune disease was not found more frequently in blood relatives than in spouse controls. Blood relatives did have a modest, although not significant, excess of rheumatic heart disease. For cancer analyses, comparisons with general population rates indicated no heterozygote predisposition, while direct comparisons of blood relatives to spouse controls revealed a significantly elevated cancer rate in females (rate ratio = 2.3, P < 0.003). The estimated relative risk of cancer for female CVID heterozygotes was most elevated in the 45–69‐year‐old age group. It is arguable whether comparisons with population or spouse controls are the most appropriate for evaluating the cancer risk of CVID heterozygotes. The hypothesis that the CVID gene predisposes heterozygous female carriers to cancer may be evaluated more easily in the future when the genetic basis for CVID is better understood.
Symptom patterns and causes of somatization in men: I. Differentiation of two discrete disorders
Authors: Sigvardsson Soren , Bohman Michael , von Knorring Anne‐Liis , Cloninger C. Robert , Conneally P. M.
Published: June 2005

Two distinct patterns of somatization were identified in 807 Swedish adopted men, using comprehensive lifetime psychiatric and sick‐leave records. “Diversiform” somatizers had a high frequency of brief sickness occasions for a wide diversity of complaints, particularly pain in the head, joints, and abdomen. “Asthenic” somatizers had a lower frequency and diversity of complaints. They recuperate more slowly, however, and were more often disabled by fatigue, weakness, and minor illnesses such as upper respiratory infections. Both types of somatizers had associated psychosocial maladjustment, but they had discrete clinical patterns, with infrequent overlap. Diversiform somatizers had a higher risk of alcohol abuse, psychiatric hospitalization, and substandard income than either asthenic somatizers or non‐somatizers. Asthenic somatizers had a higher risk of divorce than either diversiform somatizers or non‐somatizers. Men with prominent somatization had an excess of psychiatric treatment for alcoholism or anxiety disorders, but, unlike female somatizers, no excess of criminality. These clinical differences suggest that the psychiatric processes associated with somatization may be qualitatively different in men and women. The method used here is generally applicable in genetic epidemiology to identify natural clinical subtypes within a heterogeneous phenotype.
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

The 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

An 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

Subjects 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

Huntington 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

A 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

Birth 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

The 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

A 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

A 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

When 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

The 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

Plasma 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

For 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

The 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

A 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

Genetic 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.