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S Williams-Blangero

Publications and source records attributed to S Williams-Blangero.

At least 37 records · Page 2Linked to original sources
PubMed1996

Genetic analysis of serum alanine transaminase activity in normal and hepatitis C virus-infected chimpanzees: an application of research-oriented genetic management.

The hepatic enzyme alanine transaminase (ALT) is a diagnostic marker for liver damage but has a considerable degree of normal variation. We used complex segregation analysis to determine whether evidence exists for major genic determination of normal ALT values in an important animal model, the chimpanzee (Pan troglodytes). Normal ALT values were available for 212 chimpanzees. Available genealogical data allowed assignment of 165 animals to a total of 19 pedigrees; 47 animals were treated as independent. A major gene explaining 60% of the phenotypic variance in normal alanine transaminase (ALT) activity was detected by complex segregation analysis. The allele for high ALT activity had a frequency of 0.20. Polygenes accounted for an additional 20% of the variation. The observation that 80% of the total phenotypic variance is attributable to genetic factors has important implications for studies that use ALT activity in assessments. Genetic analysis of change in ALT activity after inoculation with hepatitis C virus (HCV) in a subset of animals indicated that approximately 30% of the variation in response may also be attributable to genetic factors and that the estimated major locus genotypes differ in their responses. This suggests that genetic components can exert substantial influences on experimental parameters in hepatitis research.

Alanine Transaminase↗
PubMed1996

Strategies for using nonhuman primates in genetic research on multifactorial diseases.

Multifactorial diseases such as coronary heart disease, cancer, and osteoporosis are of increasing public health concern. Such diseases have a complex etiopathogenesis involving genetic and environmental factors and interactions between these factors. Nonhuman primates are uniquely suited as animal models for complex human diseases because of their close evolutionary relationship to humans. We present the rationale for using nonhuman primates as animal models in research designed to assess the genetic determinants of multifactorial diseases. Strategies and current approaches for the use of nonhuman primate models in genetic research on complex diseases are reviewed.

Animals↗
PubMed1996

Evaluation of the chimpanzee breeding program at the Southwest Foundation for Biomedical Research.

The history of the chimpanzee (Pan troglodytes) breeding colony of the Southwest Foundation for Biomedical Research was evaluated over a 24-year period to determine age at conception, breeder rearing history, maternal competence, and infant rearing history. The records of 107 breeders and 268 live births were reviewed. Of the breeders with known rearing histories, 40 were wild-born (12 male and 28 female), 16 were reared by their mothers for at least 1 month (8 male and 8 female), and 13 were removed from their mothers immediately after birth (2 males and 11 females). The age of successful mating for males ranged from 7 to 32 years and for females from 7 to 41 years, although the upper limit indicates the age of the population and not reproductive senescence. The mother's rearing history was related to her maternal competence, defined as caring for an infant for at least 1 month. Of the wild-born females, 82% (18/22) were competent mothers. For females that had been reared in captivity with their mothers for 1 to 12 months, 71% (5/7) were competent. For females that had been removed from their mothers immediately and reared in a nursery by humans, only 14% (1/7) were competent. The rearing strategies have changed during the period under consideration. The number of infants reared by their mothers increased in the 1980s, while the number of infants removed from their mothers immediately for experimental reasons decreased and dropped to zero in the 1990s. Information on the history of the breeding colony has been used to make management decisions and to determine the expectations of the Southwest Foundation chimpanzee breeding program.

Aging↗
PubMed1994

Susceptibility to ultraviolet-induced corneal sarcomas is highly heritable in a laboratory opossum model.

The laboratory opossum, Monodelphis domestica, develops hyperplasia and neoplasia of the corneal stroma after repeated exposure to low doses of ultraviolet radiation (UVR) (non-erythemic in skin). We exposed adult animals from genetically diverse families within our colony to determine whether there are any heritable components to the risk of this form of eye cancer. From about 5 months of age, animals were exposed 3 times a week to a dose of about 125 J/m2 of UVB (spectral peak = 302 nm). Thirty-three sibships (151 individuals) completed at least 30 weeks of the protocol and 137 individuals completed 45 weeks. For genetic analysis, each animal was classified at 30 and 45 weeks as affected with corneal sarcoma or not. Heritabilities were estimated for the dichotomous eye-tumor trait which was highly heritable at both time points. This eye-cancer model system is valuable as a source of material for in vitro studies of angiogenesis and neoplastic transformation, for in vivo studies of tumor therapy and prevention, and for further research on the genetic determinants of cancer.

Animals↗
PubMed1994

Major gene for percent of oxygen saturation of arterial hemoglobin in Tibetan highlanders.

This report employs a statistical genetic approach to analyze quantitative oxygen transport variables in a high-altitude (4,850-5,450 m) native Tibetan population and demonstrates the presence of a major gene influencing % O2 saturation of arterial hemoglobin. This result suggests the hypothesis that individuals with the dominant allele for higher % O2 saturation have a selective advantage at high altitude. Studies of the biologically distinctive Himalayan and Andean populations have greatly influenced thinking about ongoing human evolution and adaptation; this is the first statistical evidence for a major gene enhancing oxygen transport in a high-altitude native population.

Adaptation, Physiological↗
PubMed1994

Genetic analysis of ultraviolet radiation-induced skin hyperplasia and neoplasia in a laboratory marsupial model (Monodelphis domestica).

Monodelphis domestica, the laboratory opossum, develops hyperplasia and neoplasia of shaved skin after repeated exposure to ultraviolet radiation (UVR). We exposed Monodelphis from genetically diverse families within our colony to determine whether there are any heritable components to the risk of two distinct skin lesion phenotypes-melanocytic nevus (MN) and advanced hyperkeratosis (HK). From about 5 months of age, animals were shaved and exposed three times a week to a dose of about 125 J/m2 of UVR (spectral peak, 302 nm; range, 280-400 nm). Of 33 sibships (151 individuals) that completed at least 30 weeks of the protocol, 137 completed 45 weeks. For genetic analyses, each animal was classified at 30 and 45 weeks as affected with MN and HK or not affected. Heritabilities were estimated using a variance decomposition approach. Susceptibility to MN showed no significant evidence for a genetic component at 30 or 45 weeks. In sharp contrast, susceptibility to HK was under virtually complete genetic control (heritability, 0.999; P < 0.001) at 30 weeks, and had a moderately high heritability (0.702; P < 0.001) at 45 weeks. We conclude that this model has great potential for identifying genes that confer susceptibility to UVR-induced skin lesions and for investigating environmental factors that may contribute to the increasing incidence of skin cancer in human populations.

Animals↗
PubMed1994

Heritabilities of clinical chemical traits in chimpanzees.

Clinical chemical measures are commonly used biomarkers of health status in nonhuman primates and may also serve as important covariates or outcome variables in experimental protocols. There is a considerable range of normal variation in most clinical chemical traits and the determinants of this variation have been relatively unexplored in nonhuman primates used as animal models in biomedical research. This study assesses the evidence for genetic determinants of normal variation in nine clinical chemical traits (blood urea nitrogen, creatinine, potassium, sodium, CO2, glucose, albumin, globulin, and total cholesterol concentrations) in an important animal model, the chimpanzee. We found significant moderate heritabilities for potassium, sodium, albumin, globulin, and total cholesterol. The results provide information useful for addressing issues in both genetic management and experimental research.

Age Factors↗
PubMed1993

Multivariate genetic analysis of apo AI concentration and HDL subfractions: evidence for major locus pleiotropy.

A major locus influencing apolipoprotein AI (apo AI) serum levels was detected using data from the Donner Laboratory Family Study. This locus accounts for 46% of the phenotypic variability in apo AI levels. Multivariate segregation analysis revealed that this major locus also has significant pleiotropic effects on the relative distribution of high density lipoproteins.

Apolipoprotein A-I↗
PubMed1993

Research-oriented genetic management of nonhuman primate colonies.

Genetic management is an important component of the general management of nonhuman primate colonies. However, standard genetic management techniques were developed primarily to address the goals of population conservation, particularly in zoo situations. The special needs of colonies that produce animals for biomedical research have not previously been fully addressed and the great potential of genetic management in the research environment remains to be realized. A research-oriented genetic management approach balances long-term breeding goals and current and future experimental needs, yielding a comprehensive overall colony management program. Pedigree information, genetic markers (e.g., serum proteins, red blood cell enzymes, restriction fragment length polymorphisms, and single-locus microsatellites), and quantitative traits (e.g., routinely gathered clinical chemical values, weights, and blood pressures) can be used alone or in combination to estimate genetic variability in the colony and to characterize animals for experimentally relevant traits. The statistical power of experiments using nonhuman primates can be improved when animals are selected on the basis of their genetic values or genotypes for experimentally relevant traits because the quantified genetic variation among subjects can then be minimized. The incorporation of experimental needs into the overall genetic management plans for captive breeding colonies helps ensure the long-term viability of colonies for meeting the demands of both breeding and research.

Animals↗
PubMed1993

Genetic analysis of hematological traits in chimpanzees (Pan troglodytes).

Hematological traits are commonly assessed markers of health status that have been used in a large number of anthropological studies, especially those focusing on high-altitude adaptation. Despite the wealth of literature on environment-associated variation in these traits, relatively few studies have dealt with the underlying genetic components of hematological measures. The purpose of this study is to estimate heritabilities for eight hematological traits using data obtained from a large pedigreed chimpanzee colony. Seven of the eight hematological traits exhibited significant heritabilities, ranging from h2 = 0.308 for mean cell volume to h2 = 0.834 for red blood cell count. The use of multiple measures per individual proved to be essential for the accurate estimation of heritabilities. We conclude that the underlying genetic variation in hematological traits should be considered when these measures are used in study protocols.

Animals↗
PubMed1993

Quantitative genetics of relative organ weight variation in captive baboons.

Anthropoid phylogeny has been characterized by dramatic increases in relative brain size. Given the importance of genetic mechanisms in evolution, quantitative genetic analyses of the biological concomitants of relative brain size variation should greatly augment our understanding of this phylogenetic phenomenon. In humans the brain is often linked metabolically with three other organs--heart, kidneys, and liver--that together account for most of the total basal metabolic rate. Because the weights of these four organs are proportional to their individual organ metabolic rates, their summed weights have been used by previous researchers as a proxy measure for their composite organ metabolic rate. We have conducted a quantitative genetic analysis of variation in the relative weights of these four organs in a population of captive baboons from the Southwest Foundation for Biomedical Research. These analyses were performed on loge-transformed organ weights available for 601 animals, 307 of which were assigned to 25 pedigrees containing 2 to 49 members; the remaining 294 animals were treated as independent individuals. Moderate but statistically significant (p < 0.005) heritabilities were estimated for all four organ weights: h2brain = 0.409 +/- 0.147, h2heart = 0.386 +/- 0.184, h2kidneys = 0.468 +/- 0.152, and h2liver = 0.600 +/- 0.160. Significant (p < 0.05) additive genetic correlations were estimated between brain and liver weights (rho G = 0.568) and between liver and kidney weights (rho G = 0.858). Significant (p < 0.05) environmental correlations were identified for heart and kidney weights (rho E = 0.551) and for liver and kidney weights (rho E = 0.684). Our results clearly demonstrate that the four organ weights have substantial heritable components that, because of their similar magnitudes, are probably equally susceptible to selection. However, the patterns of intercorrelation revealed by our analyses of the genetic and environmental correlation matrices indicate that, of the four organs composing the proxy measure of organ metabolic rate, only the liver and the kidneys are likely to exhibit correlated responses to selection for increased relative brain size such as that observed in the anthropoid fossil record.

Analysis of Variance↗
PubMed1993

A comparison of three methods for assessing Amerindian admixture in Mexican Americans.

Epidemiologic studies have revealed that Mexican Americans experience an excess of non-insulin-dependent diabetes mellitus, gallbladder disease, and obesity relative to non-Hispanic whites. It has been hypothesized that the greater susceptibility of Mexican Americans to these disorders may be related to their greater degree of Amerindian genetic admixture. We evaluate the comparability of three different methods of assessing individual genetic admixture in Mexican Americans. Subjects were enrolled as part of the San Antonio Heart Study and were examined between 1979 and 1988 (n = 3301). Three different methods were used to assess Amerindian admixture: we queried subjects about their ancestors' ethnic origin, we measured subjects' skin color, and we estimated genetic admixture directly by analysis of polymorphic blood markers. These measures were generally poorly correlated with each other, with the highest correlations observed between skin color and proportion of Mexican-origin grandparents. In men, none of these three measures of genetic admixture was associated with the prevalence of diabetes, gallbladder disease, or obesity. In women, consistent positive associations were observed between admixture and all three diseases, regardless of the admixture measure used (ie, disease prevalence was higher among women with more Amerindian admixture). In both sexes, height was negatively correlated with all three measures of admixture, and admixture was also significantly correlated with body mass index and central adiposity in women. These data suggest that the three measures considered may assess different dimensions of admixture, but that for epidemiologic research, no one may be claimed to be superior to the others.

Adult↗
PubMed1992

Genetic diversity of laboratory gray short-tailed opossums (Monodelphis domestica): effect of newly introduced wild-caught animals.

The colony of gray, short-tailed opossums (Monodelphis domestica) at the Southwest Foundation for Biomedical Research, the primary supplier of this species for research purposes, was founded with nine animals trapped in 1978 in the state of Pernambuco, Brazil. Since 1984, 14 newly acquired founders from the state of Paraiba, Brazil have contributed to the gene pool of the colony. The animals from Paraiba and their descendants are significantly larger than the founders from Pernambuco and their descendants. The two groups also differ significantly in several measurements of morphologic traits. The changes in proportional contribution of each founder to the colony, and changes in inbreeding coefficients during the colony's history, are evaluated. Using previously established markers and three newly identified markers (ACP2, APRT, and DIA1), we show that the Paraiba-derived animals differ significantly from the original founders in allele frequencies and heterozygosity. The genetic diversity of the colony has been substantially increased by acquisition of the new founders from Paraiba. The colony is highly polymorphic, with 22.2% of loci surveyed by protein electrophoresis being variable. We conclude that the genetic differences between populations and among projects within the colony should be considered in future colony management procedures and in selection of experimental subjects.

Alleles↗
PubMed1992

Quantitative genetic analysis of skin reflectance: a multivariate approach.

Skin color is a polygenically determined quantitative trait. Although it has been used extensively in studies of between-population variation, there have been relatively few studies of the inheritance of skin color. In this article we use measurements on 359 members of the Jirel population of eastern Nepal to assess the heritabilities and additive genetic correlations of three skin reflectance measures. Skin color was measured at the upper inner arm site at three wavelengths. A maximum likelihood approach was used to estimate sex and age effects on skin reflectance, heritabilities, and phenotypic variances at each wavelength and both additive genetic and environmental correlations between wavelengths. This technique incorporated information from 36 pedigrees with 2-25 members and 173 independent individuals. Likelihood ratio tests were used to assess the significance of specific variance/covariance components. The results indicate that skin reflectances are moderately heritable at all three wavelengths. The pairwise phenotypic correlations ranged from 0.76 to 0.88. The observed additive genetic correlations were not significantly different from 1.00, suggesting that the same loci influence variation at each wavelength. This evidence for relatively complete pleiotropy implies that measurements at multiple wavelengths yield little additional genetic information, although they may be useful for reducing measurement error. Based on estimates of the genetic and phenotypic covariance matrices, we determined that skin reflectance measurements are expected to provide only as much information for assessing local between-population genetic variation as a single two-allele polymorphic marker. Therefore microevolutionary studies based on skin color variation should be viewed with caution.

Adolescent↗
PubMed1991

Skin color variation in eastern Nepal.

The purpose of this paper is to provide skin color data on several endogamous groups of eastern Nepal and to demonstrate genetic microdifferentiation in skin color. Skin reflectance measures were taken at the upper inner arm and forehead sites, using the British DSL Model 99 Reflectance Spectrophotometer fitted with blue, green, and red filters. Measurements on 484 males representing six endogamous groups (Jirel, Sunwar, Sherpa, Tamang, Brahman, Chetri) were utilized. After adjusting for group-specific age effects, multivariate likelihood ratio permutation tests were used to assess ethnic differences in skin reflectance means and covariance matrices. Ethnic group membership had a highly significant effect on skin color at the upper inner arm site and at the forehead site. Differential tanning responses among groups were also detected and may represent the influence of genotype-environment interaction on reflectance traits. Mahalanobis distance analysis revealed patterns of microdifferentiation that are inconsistent with oral historical accounts. Little support was found for the ethnohistorical belief that Jirels are a hybrid group descended from Sunwars and Sherpas, even though this scenario is supported by linguistic, anthropometric, and dermatoglyphic data. We suggest that while reflectometric studies of skin pigmentation may be useful in assessing the macrodifferentiation of human populations, the use of skin color in differentiation studies at the local population level needs to be carefully evaluated.

Adolescent↗
PubMed1991

Variation in Lp(a) levels and apo(a) isoform frequencies in five baboon subspecies.

Elevated levels of lipoprotein (a) [Lp(a)] are positively correlated with risk of cardiovascular disease and are thought to be a function of allelic variation in apo(a), the unique protein component of Lp(a). In this article we examine subspecies variation in Lp(a) levels and apo(a) isoforms in the baboon. Breeding populations of the five subspecies (Papio hamadryas hamadryas, P.h. cynocephalus, P.h. ursinus, P.h. papio, and P.h. anubis) of common long-tailed baboons are maintained at the Southwest Foundation for Biomedical Research. Serum samples were obtained from at least 20 unrelated animals of each subspecies. Twelve different size isoforms (including the null) of apo(a) were identified across the five subspecies. These isoforms act as alleles; a maximum likelihood method was used to obtain the allele frequencies. Significant differences in apo(a) isoform frequencies were found between subspecies (chi 2(44) = 163.10, p less than 0.0001). Quantitative levels of Lp(a) also differed among subspecies. We evaluated the correlation between genetic distances calculated using the quantitative Lp(a) levels and the apo(a) isoform data. Observed genetic relationships among the subspecies are consistent with the present-day geographic distribution and information from other marker protein systems. The findings indicate that the marker apo(a) may have great utility in both evolutionary and biomedical studies.

Animals↗