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Bennett Dyke

Publications and source records attributed to Bennett Dyke.

13 recordsLinked to original sources

Fasting insulin and obesity-related phenotypes are linked to chromosome 2p: the Strong Heart Family Study.

To localize quantitative trait loci for insulin metabolism and obesity, genome scans/linkage analyses were performed on >900 members of 32 extended families participating in phase 3 of the Strong Heart Study, an investigation of the genetic and environmental determinants of cardiovascular disease in American-Indian populations from Arizona, Oklahoma, and North and South Dakota. Linkage analyses of fasting insulin and two obesity-related phenotypes, BMI and percent fat mass, were performed independently in each of the three populations. For log fasting insulin, we found a genome-wide maximum, robust logarithm of odds (LOD) score of 3.42 at 51 cM on chromosome 2p in the Dakotas. Bivariate linkage analyses of log fasting insulin with both BMI and fat mass indicate a situation of incomplete pleiotropy, as well as several significant bivariate LOD scores in the Dakotas.

Adolescent↗

Recruitment and community interactions in the GOCADAN study.

OBJECTIVES: To study heart and vascular disease in Alaskan Eskimos. To identify risk factors for CVD in Norton Sound Eskimos. STUDY DESIGN: Participatory research. In this paper, procedures for selection and enrollment and providing feedback and referrals are described. Our working relationships with the Norton Sound Health Corporation (NSHC) Board, the village councils, individuals, and communities are also described. METHODS: This study was conducted in the Norton Sound region of Alaska. The participants were members of Alaskan Eskimo families. RESULTS: Procedures were formed for selecting and enrolling extended families into the study and for working with the NSHC Board, the village councils, and individual participants. The average participation was 82.6% of the age-eligible villagers in seven villages. A four-level referral system was designed. Test results were provided to participants in the form of letters, with duplicates sent to health care providers and medical records. A senior researcher returned to the village to explain the results to the participants. CONCLUSIONS: Principles of participatory research applied and developed in this study led to successful screening of 1214 Eskimos in nine villages between October 2000 and June 2004. This partnership developed into a relationship with the community, in which researchers and the communities mutually participated in the study, from the initiation of the design to the return of the data to the individuals, communities, and health care providers.

Adult↗

Dietary intakes vary with age among Eskimo adults of Northwest Alaska in the GOCADAN study, 2000-2003.

Dietary factors influence the development of cardiovascular disease (CVD). The diet of Alaskan Eskimos differs from that of other populations. We surveyed Eskimo adults in Northwest Alaska to document their usual dietary intakes, differences based on gender and age, and sources of selected nutrients, and to generate appropriate dietary advice to reduce CVD. Interviewers surveyed 850 men and women 17-92 y old, using a quantitative food-frequency instrument. We observed many significant (chi(2) analysis P < 0.05) differences in nutrient intakes among 3 age-groups. Energy intake from carbohydrate was negatively related to participant age-group (P < or = 0.01). Energy intake from all fats (P < 0.001) and polyunsaturated fat (P < or = 0.01) was positively related to age-group among both men and women in contrast to other studies in which age differences were either not observed or decreased with age. Native foods were major sources of monounsaturated and polyunsaturated fats, including 56% of (n-3) fatty acids primarily from seal oil and salmon. However, Native foods contributed significantly less to the diets of young adults than to those of elders, especially among women. Store-bought foods were the main sources of energy, carbohydrate, fat, saturated fat, and fiber for all adults. Based on their nutrient density and potential to inhibit CVD, continued consumption of traditional foods is recommended. Variations in intake by age may portend changing eating patterns that will influence CVD as participants age. These data will contribute to understanding dietary risk factors for cardiovascular disease in this population.

Adolescent↗

A genetic and epidemiologic study of cardiovascular disease in Alaska natives (GOCADAN): design and methods.

This article is a report of the design and methods of the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study. This longitudinal, population-based study was initiated to investigate the genetic determinants of cardiovascular disease and its risk factors. Between October 2000 and April 2004, this family study enrolled 1,214 Eskimos from several coastal villages in the Norton Sound region of Western Alaska. Examinations included a physical, laboratory determinations, and measures of subclinical disease. This study will generate a genome-wide scan for loci influencing cardiovascular disease-related traits. Relations between subclinical atherosclerosis and markers of inflammation will be examined using historic and newly drawn samples. The study will provide data on CVD prevalence, risk factors and the relative contribution of genetic and environmental determinants in Alaska Native peoples. Data from this study will contribute to the delivery of health-care and prevention of CVD in Alaska Eskimos and other populations.

Adult↗

A quantitative trait locus influences coordinated variation in measures of ApoB-containing lipoproteins.

Lipoprotein phenotypes are known to be strongly intercorrelated. These intercorrelations are due to genetic and environmental effects on common metabolic pathways. The purpose of this study was to determine if we could localize genes that exert pleiotropic effects on multiple related lipoprotein traits in humans. Using data from the San Antonio Family Heart Study, we extracted principal components from a set of 12 intercorrelated lipoprotein traits that included phenotypes reflecting lipid and protein concentrations and size distributions for LDLs and HDLs. Five principal components were extracted from the data and all were significantly heritable (h(2) = 0.41-0.57). When subjected to linkage analyses, only one, Component 5, returned a LOD score > or = 3 (LOD score was 3.0 at 38cM on chromosome 15; genome-wide P-value = 0.039). LDL median diameter (-0.529), non-HDLC (-0.422), and ApoB (-0.403) concentrations were the only traits with loadings (absolute value) >0.4, suggesting Component 5 is related to LDL size or perhaps more generally to beta-lipoprotein metabolism. Surprisingly, none of the 12 original lipoprotein traits had a LOD >1 in this region of chromosome 15. These data provide evidence for a novel gene, influencing beta-lipoprotein phenotypes, whose effect(s) is detected only when several lipoprotein traits are considered together.

Adult↗

Genetics and caging type affect birth weight in captive pigtailed macaques (Macaca nemestrina).

The heritability of birth weight was estimated in 3,562 captive pigtailed macaques using 30 years of breeding and pedigree records. Based on a pedigree of over 12,000 animals, quantitative genetic analyses were performed using statistical variance decomposition methods. The model included additive genetic effects, cytoplasmic genetic effects, birth environment, shared maternal environment, and unmeasured environmental effects. The results demonstrated a strong (h(2) = 0.51) heritable component of birth weight overall, and included significant additive genetic heritability (h(2) = 0.23), and cytoplasmic heritability (h(2) = 0.09). In addition, a significant effect of birth location and cage type was identified, explaining an additional 6% of birth weight variance. The use of a nonhuman primate model for studying the effects of genes on birth weight eliminated many of the problems associated with confounding variables in human studies, and allowed for the quantification of a heritable component of birth weight.

Animals↗

Genetic determination of HDL variation and response to diet in baboons.

We fed 634 baboons three diets to assess the separate effects of increasing dietary fat and cholesterol intakes on three independent measures of HDL phenotype: concentrations of HDL cholesterol and apoAI, and size distributions of HDL cholesterol. Increasing dietary fat significantly increased concentrations of HDL cholesterol and apoAI (both, P<0.0001), but did not affect HDL particle sizes, whereas increasing dietary cholesterol increased HDL cholesterol (P<0.0001) concentrations and HDL particle sizes (P=0.08), but did not affect apoAI concentrations. A substantial proportion of variation in each of the HDL traits was influenced by genes (heritabilities ranged from 25 to 61%) and a common set of genes influenced HDL variation on each of the diets (genetic correlations ranged from 0.64 to 1.0). However, genes exerted a smaller effect on HDL response to changes of dietary fat and of dietary cholesterol. Therefore, dietary fat and cholesterol alter HDL levels and characteristics, but the dietary responses are not strongly mediated by additive genetic effects.

Animals↗

A major gene influences variation in large HDL particles and their response to diet in baboons.

Some baboons accumulate appreciable amounts of large apoE-rich HDLs (HDL(1)) which are similar to those reported in humans with several different dyslipoproteinemias. We estimated HDL(1) cholesterol concentrations by gradient gel electrophoresis of serum samples obtained from 634 pedigreed baboons fed with three diets differing in levels of fat and cholesterol. The HDL(1) trait was highly heritable on each diet (0.390< or =h(2)< or =0.528). Segregation analyses yielded significant evidence that a single major gene plus polygenes affected HDL(1) on a high-fat low-cholesterol diet. The major gene explained approximately 56% of total trait variance and 90% of the additive genetic variance in HDL(1) levels in these baboons. Bivariate one-locus segregation analyses indicated that this major gene exerts significant pleiotropic effects on a number of traditional HDL traits on all three diets, including HDL size distributions, and concentrations of HDL-C, apoAI, and apoE. Linkage analyses showed that this major gene was not located in chromosomal regions that contain six candidate genes whose protein products are important to HDL metabolism (LCAT, CETP, APOA1, APOE, ABCA1, LIPC). Our results suggest this major gene in baboons plays a pivotal role in HDL metabolism, but is unlikely to code for any of the proteins previously implicated in studies of human HDL(1).

Animals↗

Lifespan in captive baboons is heritable.

The effects of aging are evident in multiple organ systems, tissues, cell types, and molecules; all complex phenotypes affected by multiple shared and unique environmental factors and genes, which makes identifying the role of genetics in human aging difficult. Researchers have used yeast, nematodes, fruit flies, and mice to search for genes that influence the aging process. Given the phylogenetic distance and anatomic and physiologic dissimilarities of these organisms from humans, directly extrapolating these results to our species is problematic. However, nonhuman primates have a high degree of genetic, anatomic and physiologic similarity with humans and, thus, they may assist in the detection, characterization, and identification of genetic and environmental influences on human aging. Our goal is to demonstrate that effects of genes on variation in lifespan, a surrogate measure of aging, can be detected in a nonhuman primate species. Using variance component analysis, heritability of age at death was estimated to be 0.23+/-0.08 (P=0.0003) in 674 baboons from the Southwest Foundation for Biomedical Research (SFBR). This research demonstrates that lifespan is under partial genetic control. Given these findings, we believe that the baboon has potential as a model of human aging.

Analysis of Variance↗

Genetic management of nonhuman primates.

Genetic management is widely recognized as a critical component of the overall management of captive nonhuman primate colonies which produce animals for biomedical research. In this paper, we review the roles of conservation-oriented genetic management, research-oriented genetic management, genetic management at the level of taxomomic class, genetic management at the level of the population, and quantitative genetic analysis in comprehensive genetic management programs for nonhuman primate colonies. We conclude that genetic management is crucial for maintaining nonhuman primate populations suitable for genetic research on normal and disease-related phenotypes. In addition, for research programs that do not have specific genetic objectives, genetic management is essential to facilitate the selection of samples of well-matched unrelated animals for experimental purposes.

Animals↗

Common set of genes regulates low-density lipoprotein size and obesity-related factors in Alaskan Eskimos: results from the GOCADAN study.

Increasing incidence of cardiovascular disease in traditionally low-risk Alaskan Eskimos is a cause for concern. The purpose of this study was to examine the genetic and environmental correlations of low-density lipoprotein (LDL) subfractions with obesity-related factors in Alaskan Eskimos, using data from the first 954 participants of the Genetics of Coronary Artery Disease in Alaska Natives Study. Estimates of genetic and environmental influence were calculated using a maximum likelihood variance component method implemented in SOLAR. Mean values of weight, body mass index (BMI), and waist were 73.4 +/- 0.5 kg, 27.6 +/- 0.2 kg/m2, and 88.0 +/- 0.4 cm, respectively. LDL, and its small (LDL1), medium (LDL2), and large (LDL3) subfractions, had mean values of 115.8 +/- 1.2 mg/dl, 8.3 +/- 0.4 mg/dl, 19.6 +/- 0.8 mg/dl, and 71.5 +/- 1.5 mg/dl, respectively. Bivariate analysis displayed significant genetic correlations between LDL subfractions and obesity-related factors: LDL1 with BMI (rhoG = 0.67, P < 0.05), waist (rhoG = 0.80, P < 0.001), and subscapular and tricep skinfolds (rhoG = 0.93, P < 0.005, and rhoG = 0.78, P < 0.05, respectively); LDL2 with BMI (rhoG = 0.52, P < 0.05), waist (rhoG = 0.46, P < 0.05), and tricep skinfold (rhoG = 0.60, P < 0.05); and mean LDL size with BMI (rhoG = -0.36), waist (rhoG = -0.42,), and subscapular and tricep skinfolds (rhoG = -0.44 and -0.43, respectively) (P < 0.005). These results show that a common set of genes is influencing LDL size and obesity-related factors in Alaskan Eskimos.

Adolescent↗