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S Williams-Blangero

Publications and source records attributed to S Williams-Blangero.

At least 19 recordsLinked to original sources
PubMed2006

Comparative analysis of cell phenotypes in different severe clinical forms of Chagas' disease.

The understanding of the role of the immune response in the development of gastrointestinal and cardio-digestive (CD) forms of Chagas disease has received little attention. In this paper, the commitment of each leukocyte population of peripheral blood to the production of IFN-gamma, TNF-alpha, IL-12, IL-4, IL-5 and IL-10 was studied in patients with the CD form of Chagas disease. The data show that cells from patients with the CD form of the disease have distinct cytokine profiles when compared with the other clinical forms of Chagas disease and suggest that eosinophils are the major source of cytokine production in this clinical entity. The data presented in this paper demonstrate that patients with CD form can be distinguished from patients with gastrointestinal or cardiac forms of the disease by the distinct cytokine profile of peripheral blood cells.

Adult↗
PubMed2003

Spurious genotypes in female nematodes resulting from contamination with male DNA.

Females of many invertebrates contain stored sperm or fertilized eggs or both, causing potential genotyping errors. We investigated errors caused by male DNA contamination by amplifying 5 microsatellites in DNA isolated from various tissue types in the nematode Ascaris lumbricoides. We observed additional alleles in 30/135 uterus-derived samples when compared with muscle controls, resulting in 20/135 (15%) incorrect genotypes and an underestimation of inbreeding. In contrast, we observed additional alleles in only 5/143 ovary-derived samples, resulting in 4/143 (3%) incorrect genotypes and no significant influence on inbreeding estimates. Because uterus constitutes approximately 17% of a female's organ weight, a substantial proportion of samples isolated from female tissue may contain male-derived DNA. Male contamination is easily avoided when using large nematodes such as A. lumbricoides. However, we urge caution for studies using DNA isolated from small invertebrates that store sperm or fertilized eggs or both.

Animals↗
PubMed2002

Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil.

This study quantifies the influence of shared household and kinship on egg counts during Schistosoma mansoni infection in a sample from rural Brazil. Detailed genealogic information allowed assignment of 597 individuals to 6 multihousehold pedigrees residing in 145 households. A variance component method was used to partition egg counts into shared household, additive genetic, and individual-specific environmental effects. Host additive genetic effects consistently accounted for a large proportion of the variation in egg counts: 43% in an unadjusted model and 40% in model adjusted for covariates. In a model that examined the confounding of shared household with kinship, additive genetic effects still accounted for 27% of the variation in egg counts and shared household only 12%. The consistently important role for host additive genetic factors on the variation in egg counts points to new ways of modeling and understanding the mechanisms that contribute to trait variation during infection with S. mansoni.

Animals↗
PubMed2001

Genetic analysis of quantitative traits in highly ascertained samples: total serum IgE in families with asthma.

The objective of this study was to compare the effect of an approximate ascertainment correction using proband phenotypes with heuristic corrections based on sample trait means and on published "standard" population values. Data were from the Collaborative Study on the Genetics of Asthma, which comprises 225 families ascertained through sib pairs affected with asthma. In variance component linkage analysis of IgE no lod scores greater than 3.0 were observed, either with or without several attempted corrections for ascertainment. The ascertained nature of the sample may have compromised the power to detect linkage to a quantitative trait (IgE) associated with the focal phenotype (asthma).

Adult↗
PubMed2001

Exposure to Schistosoma mansoni infection in a rural area in Brazil. II: household risk factors.

A number of studies have pointed out the potential importance of the household in the transmission of schistosomiasis. The clustering of domestic activities associated with water collection, storage, and usage can result in the sharing of transmission sites and infective water contact behaviours. In this study, we employed a variance component method to estimate effects due to individual risk factors and shared residence on the variance in faecal egg counts during Schistosoma mansoni infection. A suite of covariates, which included demographic, socioeconomic, water supply, and water contact behaviour terms, contributed 15% to the variance in faecal egg counts. Shared residence alone accounted for 28% of the variance in faecal egg excretion. When both the suite of covariates and shared residence were considered in the same model, shared residence still contributed 22% to the variance in infection intensity. These results point to the importance of shared residence as a means of capturing the complex interrelationship between shared demographic, socioeconomic, physical environmental, and behavioural factors that influence transmission of schistosomiasis at the household level.

Adolescent↗
PubMed1999

Percent of oxygen saturation of arterial hemoglobin among Bolivian Aymara at 3,900-4,000 m.

A range of variation in percent of oxygen saturation of arterial hemoglobin (SaO2) among healthy individuals at a given high altitude indicates differences in physiological hypoxemia despite uniform ambient hypoxic stress. In populations native to the Tibetan plateau, a significant portion of the variance is attributable to additive genetic factors, and there is a major gene influencing SaO2. To determine whether there is genetic variance in other high-altitude populations, we designed a study to test the hypothesis that additive genetic factors contribute to phenotypic variation in SaO2 among Aymara natives of the Andean plateau, a population geographically distant from the Tibetan plateau and with a long, separate history of high-altitude residence. The average SaO2 of 381 Aymara at 3,900-4,000 m was 92+/-0.15% (SEM) with a range of 84-99%. The average was 2.6% higher than the average SaO2 of a sample of Tibetans at 3,800-4,065 m measured with the same techniques. Quantitative genetic analyses of the Aymara sample detected no significant variance attributable to genetic factors. The presence of genetic variance in SaO2 in the Tibetan sample and its absence in the Aymara sample indicate there is potential for natural selection on this trait in the Tibetan but not the Aymara population.

Adaptation, Physiological↗
PubMed1999

Genetic analysis of susceptibility to infection with Ascaris lumbricoides.

Epidemiologic studies of helminthic infections have shown that susceptibility to these parasites frequently aggregates in families, suggesting the possible involvement of genetic factors. This paper presents a genetic epidemiologic analysis of Ascaris lumbricoides infection in the Jirel population of eastern Nepal. A total of 1,261 individuals belonging to a single pedigree were assessed for intensity of Ascaris infection at two time points. Following an initial assessment in which all individuals were treated with albendazole, a follow-up examination was performed one year later to evaluate reinfection patterns. Three measures of worm burden were analyzed, including eggs per gram of feces, direct worm counts, and worm biomass (weight). For all traits, variance component analysis of the familial data provided unequivocal evidence for a strong genetic component accounting for between 30% and 50% of the variation in worm burden. Shared environmental (i.e., common household) effects account for between 3% and 13% of the total phenotypic variance.

Adolescent↗
PubMed1998

Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara.

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

Adaptation, Physiological↗
PubMed1998

Attitudes towards helminthic infection in the Jirel population of eastern Nepal.

Intestinal worm infections, including roundworm, hookworm, and whipworm, are major international health concerns, affecting approximately one fourth of the world's population. Many intervention schemes have been attempted to control these infections in heavily exposed populations, but success has been limited because individuals are readily reinfected upon renewed exposure. Few data are available concerning people's health beliefs about soil-transmitted helminthic infections in such populations. The purpose of this study was to assess health beliefs about common helminthiasis in a population experiencing moderate to high rates of infection. The focal population for the study was the Jirel population, a tribal group distributed across nine villages in the Jiri Region of Dolakha District, eastern Nepal. The results indicate that beliefs about the types, causes, and treatments of helminthic infections have been developed and reinforced by experience and empirical evidence. People's frequent inability to confirm the efficacy of drug therapy by observing worms in stools has led to dissatisfaction with biomedical approaches. Carefully planned education programs are required to alter prevailing attitudes and improve control of soil-transmitted helminthiasis in the region.

Adolescent↗
PubMed1997

Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives.

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9-82 years of age and 542 Bolivian Aymara 13-94 years of age, native residents at 3,800-4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2-7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara.

Acclimatization↗
PubMed1997

A variance component approach to dichotomous trait linkage analysis using a threshold model.

We developed and utilized a multipoint variance components method to test for linkage between a disease trait and markers on chromosome 5 in the simulated data provided in GAW10 Problem 2. We demonstrated that the discrete trait variance components method recovers unbiased estimates of quantitative trait locus (QTL) location and reasonable estimates of effect size. We also showed that dichotomization of (a continuous trait such as) Q1 diminished the power to detect linkage compared to direct analysis of Q1, and that extended pedigree analyses provided superior power to detect linkage compared to those in nuclear families.

Analysis of Variance↗
PubMed1997

Genetics of adult body mass and maintenance of adult body mass in captive baboons (Papio hamadryas subspecies).

Adult body mass and changes in mass during an individual's life are important indicators of general health and reproductive fitness. Therefore, characterization of the factors that influence normal variation in body mass has important implications for colony management and husbandry. The main objective of this study was to quantify the genetic contribution to adult body mass and its maintenance in baboons. Intra-individual mean and variance in body mass were calculated from multiple weight measures available for each of 1,614 animals at least 10 years of age. Heritabilities were estimated using maximum likelihood methods. Mean adult body mass had a significant heritability (50%) as did variance in adult body mass (12%). The sexes differed in several respects: on average females were smaller than males and had greater variability in adult body mass; mean and variance in body mass increased with age in females only; and number of offspring showed a significant positive relationship with body mass in females only. There were significant differences between subspecies in body mass as well as ability to maintain body mass. These results indicate that there is a significant genetic influence on body mass and its maintenance, and suggest that different factors influence changes in body mass with age as well as body mass maintenance in male and female baboons.

Animals↗
PubMed1997

Advantages and limitations of nonhuman primates as animal models in genetic research on complex diseases.

The genetic similarity between humans and nonhuman primates makes nonhuman primates uniquely suited as models for genetic research on complex physiological and behavioral phenotypes. By comparison with human subjects, nonhuman primates, like other animal models, have several advantages for these types of studies: 1) constant environmental conditions can be maintained over long periods of time, greatly increasing the power to detect genetic effects; 2) different environmental conditions can be imposed sequentially on individuals to characterize genotype-environment interactions; 3) complex pedigrees that are much more powerful for genetic analysis than typically available human pedigrees can be generated; 4) genetic hypotheses can be tested prospectively by selective matings; and 5) essential invasive and terminal experiments can be conducted. Limitations of genetic research with nonhuman primates include cost and availability. However, the ability to manipulate both genetic and environmental factors in captive primate populations indicates the promise of genetic research with these important animal models for illuminating complex disease processes. The utility of nonhuman primates for biomedical research on human health problems is illustrated by examples concerning the use of baboons in studies of osteoporosis, alcohol metabolism, and lipoproteins.

Animals↗
PubMed1997

Genetic epidemiology of seropositivity for Trypanosoma cruzi infection in rural Goias, Brazil.

Chagas' disease is a zoonotic disease found throughout Latin America. Despite control programs in many of the affected countries, infection with Trypanosoma cruzi continues to be a major public health concern. In Brazil alone, approximately 53 million people live in endemic areas. Research with humans and with animal models indicates that there is variation in susceptibility to infection with T. cruzi. The reasons for this variation are not known although several studies have implicated genetic factors. An indirect immunofluorescence assay was used to assess seropositivity for T. cruzi infection in 716 adults from the municipality of Posse, Goias, Brazil. Detailed genealogic information was gathered at the time of sampling, which allowed assignment of 525 individuals to 146 pedigrees containing between two and 103 individuals; the remaining 191 unrelated individuals were retained as independents in the analysis. Using a maximum likelihood variance decomposition approach, we performed quantitative genetic analyses to determine if genetic factors could partially account for the observed pattern of seropositivity. The maximum likelihood estimate of the heritability of T. cruzi infection was 0.56 +/- 0.27 (mean +/- SE), indicating that genetic factors account for more than half of the observed variation in infection status. An additional 23% of the variation (c2 = 0.23 +/- 0.09) is attributable to the effects of shared environment, as assessed by common household. The results indicate that genetic factors play an important role in determining epidemiologic patterns of T. cruzi infection. Further characterization of these genetic factors may suggest new biologic areas to be targeted by prevention and intervention programs.

Adolescent↗
PubMed1997

Quantitative genetic analysis of susceptibility to hookworm infection in a population from rural Zimbabwe.

Overdispersion is a common feature of population distribution patterns for hookworm infection in humans. Genetic factors may be partially responsible for this observed increased susceptibility in a fraction of the exposed population. However, the hypothesis that there are genetic components to susceptibility to this infectious disease has not been tested explicitly. The purpose of this study is to quantify the influence of genetic factors on patterns of hookworm infection in a rural population in Zimbabwe. A quantitative measure of hookworm load, number of hookworm eggs per gram of feces, as determined by the Kato thick smear technique, was available for 289 individuals. Of these, 279 individuals were members of 62 nuclear families and 10 were independent individuals. We analyzed the hookworm data in combination with the pedigree structure of the sampled individuals using quantitative genetic analysis techniques. Using this variance decomposition approach, we estimated the heritability of hook worm load to be 0.37 +/- 0.09 (p < 0.0001). This significant heritability indicates that 37% of the variation (after correcting for the effects of covariates) in hookworm eggs per gram observed in this population is attributable to genetic factors. The results suggest that further investigation and characterization of the genetic components influencing susceptibility to hookworm infection are warranted.

Adolescent↗
PubMed1997

Quantitative genetic analysis of arterial oxygen saturation in Tibetan highlanders.

This study was designed to test the hypothesis that genetic differences inferred from biological kinship relationships among individuals contribute to individual variation in percentage of oxygen saturation of arterial hemoglobin (SaO2) in a high-altitude native population. SaO2 data were obtained by pulse oximetry from 354 nonpregnant, healthy Tibetan residents of Pen-Dri, two rural agropastoral villages at 3800-4065 m altitude in Lhasa Municipal District, Tibet Autonomous Region, China. Statistical analyses of these data from 46 pedigrees tested the hypothesis of a significant genetic contribution to SaO2 variation. The average SaO2 was 89.4 +/- 0.2%, with a range of 76-97%. Additive genetic effects account for 44% of the interindividual phenotypic variation in SaO2 in the sample. Complex segregation analysis and variance decomposition analysis determined that 21% of the total phenotypic variation could be explained by a major gene influencing SaO2. Homozygotes for the low-SaO2 allele have a mean SaO2 of 83.6%, whereas heterozygotes and homozygotes for the high-SaO2 allele have means of 87.6% and 88.3%, respectively. This confirms findings in another Tibetan sample and extends the known geographic distribution of the major gene. These results suggest the hypothesis that individuals with the dominant allele for higher SaO2 have a selective advantage in their high-altitude hypoxic environment.

Adaptation, Physiological↗
PubMed1996

Effects of a major gene for apolipoprotein A-I concentration are thyroid hormone dependent in Mexican Americans.

Apolipoprotein A-I (apoA-I) is the principal protein component of HDL cholesterol. The thyroid hormone triiodothryonine (T3) is known to be a potent mediator of expression of the apoA-I structural gene (APOA1). Using complex segregation analysis, we detected a major gene influencing plasma concentration of apoA-I and examined its interaction with T3 serum level in Mexican Americans participating in the San Antonio Family Heart Study. Strong evidence for a major locus with two alleles (A and a) determining apoA-I level was obtained when interaction with T3 was allowed. The major gene appears not to be linked to the APOA1 structural locus. Genotypes differed significantly in their relationships to T3 level. The AA and Aa genotypes showed a positive relationship with T3 level, while the rarer aa homozygote showed a strong negative relationship with T3. The relative variance in apoA-I concentration due to this major gene varied from 56% to 18%, depending on T3 level. On average, the major gene accounts for 30% of apoA-I variation, and shared-household effects account for an additional 11%. These findings suggest that thyroid hormone has an important role in the genetic control of lipoprotein metabolism.

Adult↗