Genetic differentiation between baboon subspecies: Relevance for biomedical research

Williams‐Blangero, Sarah; VandeBerg, John L.; Blangero, John; Konigsberg, Lyle W.; Dyke, Bennett

doi:10.1002/ajp.1350200202

Cited by 72 publications

(34 citation statements)

References 25 publications

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“…Baboons (Papio hamadryas sensu lato 13,14 ) were maintained at the Southwest Foundation for Biomedical Research, a facility certified by the American Association for the Accreditation of Laboratory Animal Care, under conditions approved by the institutional animal care and use committee.…”

Section: Methods Animalsmentioning

confidence: 99%

“…We tested for the effects of sex, age, and the square of age in males and females; weight; nursery rearing; and subspecies admixture; only those covariates giving a P value Ͻ0.10 were retained in the final model for each trait. Two potential covariates found in other studies, breast fed versus formula fed 10,15 and subspecies admixture, 14 did not satisfy the requirement and were not retained in subsequent models for any of the traits.…”

Section: Major Locus Pleiotropymentioning

confidence: 97%

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Two Major Loci Control Variation in β-Lipoprotein Cholesterol and Response to Dietary Fat and Cholesterol in Baboons

Rainwater

Kammerer

Hixson

et al. 1998

ATVB

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Abstract-We explored the genetic control of cholesterolemic responses to dietary cholesterol and fat in 575 pedigreed baboons. We measured cholesterol in ␤-lipoproteins (low density lipoprotein cholesterol [LDLC]) in blood drawn from baboons while they were consuming a baseline (low in cholesterol and fat) diet, a high-saturated fat (lard) diet, and a high-cholesterol, high-saturated fat diet. In addition to baseline levels (LDLC Base ), we analyzed two variables for diet response: LDLC RF , which represents the LDLC response to increasing dietary fat (ie, high-fat diet minus baseline), and LDLC RC , which represents the LDLC response to increasing dietary cholesterol level (ie, high-cholesterol, high-fat diet minus high-fat diet). Heritabilities (h 2 ) of the 3 traits were 0.59 for LDLC Base , 0.14 for LDLC RF , and 0.59 for LDLC RC . In addition, LDLC Base and LDLC RC had a significant genetic correlation (ie, G ϭ0.54), suggesting that 1 or more genes exert pleiotropic effects on the 2 traits. Segregation analyses detected a single major locus that accounted for nearly all genetic variation in LDLC RC and some genetic variation in LDLC Base and LDLC RF and confirmed the presence of a different major locus that influences LDLC Base alone. Preliminary linkage analyses indicated that neither locus was linked to the LDL receptor gene, a likely candidate locus for LDLC. Detection of these major loci with large effects on the LDLC response to dietary cholesterol in a nonhuman primate offers hope of detecting and ultimately identifying similar loci that determine LDLC variation in human populations. (Arterioscler Thromb Vasc Biol. 1998;18:1061-1068.)

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Section: Methods Animalsmentioning

confidence: 99%

Section: Major Locus Pleiotropymentioning

confidence: 97%

Two Major Loci Control Variation in β-Lipoprotein Cholesterol and Response to Dietary Fat and Cholesterol in Baboons

Rainwater

Kammerer

Hixson

et al. 1998

ATVB

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“…The study population consisted of 319 (220 female, 99 male) members of extended baboon pedigrees (P. hamadryas 15 ) housed at the Southwest National Primate Research Center at the Southwest Foundation for Biomedical Research in San Antonio, TX, USA. The baboons were postpubertal, and ranged in age from 6 to 29 y.…”

Section: Study Populationmentioning

confidence: 99%

Genetics of leptin expression in baboons

et al. 2003

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OBJECTIVE: Leptin gene expression is higher in females than in males, and is regulated by many factors including energy intake and insulin, but little is known about the inheritance of leptin gene expression. We have investigated leptin (LEP) gene expression, to determine whether it is heritable, and whether the difference in LEP expression between males and females has a genetic component. STUDY POPULATION: A total of 319 baboons (Papio hamadryas) (220 females, 99 males) from a captive, pedigreed colony. MEASUREMENTS AND METHODS:We cloned a baboon LEP cDNA, and quantified LEP mRNA expression in baboon omental adipose tissue using a ribonuclease protection assay. In addition, we assayed circulating leptin levels, adipocyte cell volume, and weight. We used maximum likelihood-based variance decomposition methods to determine the genetic architecture of LEP levels, including testing for genotype-by-sex interaction. RESULTS: Omental LEP mRNA expression was significantly and positively correlated with weight and adipocyte cell volume in baboons. Both mRNA and plasma levels of leptin were higher in females than in males, and both measures were heritable. The results of our genetic analysis show that there was a genotype-by-sex interaction in the levels of plasma leptin, but not in omental LEP mRNA. CONCLUSIONS: As in humans, baboon leptin mRNA and protein levels are expressed at a higher level in females than in males. We detected evidence that the plasma levels were affected by genes that are differentially expressed in males and females, while the omental mRNA levels were not. This finding suggests that the genes that differentially regulate plasma leptin levels between males and females may exert their effects on post-transcriptional processes.

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“…We analyzed normal quantitative variation in HDL 1 -C, HDL 2 -C, and HDL 3 -C levels for 942 baboons (P h adryas sensu lato 35,36 Baboons were maintained on a monkey chow diet low in cholesterol (0.03 mg/kcal) and fat (4% of calories, derived from vegetable oils; referred to below as "Chow" diet). Animals were fasted overnight and blood samples were drawn from the femoral vein after immobilization with ketamine (10 mg/kg body weight).…”

Section: Animals and Blood Samplesmentioning

confidence: 99%

“…49 With this approach, we obtained simultaneous maximum likelihood estimates of the phenotypic means (), phenotypic standard deviations (), heritabilities (h 2 ), and the effects of sex, age-by-sex, age 2 -by-sex, nursery status (a dichotomous trait: baboons reared until weaning in a nursery were scored as "1" and those reared by mothers, "0"), and percent Yellow baboon admixture (method of calculation is reported elsewhere 36 ) for all 6 traits, as well as the genetic and environmental correlations between them. Before analysis, we performed a log e (ln) transformation on the HDL-C subfraction data to reduce skewness and to mitigate effects of scale on parameter estimation.…”

Section: Statistical Genetic Analysismentioning

confidence: 99%

Pleiotropy and Genotype by Diet Interaction in a Baboon Model for Atherosclerosis

Mahaney¹,

Blangero²,

Rainwater³

et al. 1999

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Abstract-We investigated dietary effects on pleiotropic relationships among 3 HDL cholesterol (C) subfractions(HDL 1 -C, HDL 2 -C, and HDL 3 -C; levels quantified by gradient gel electrophoresis) for 942 pedigreed baboons (Papio hamadryas) who were fed a basal (Chow) diet and a high cholesterol, saturated fat (HCSF) challenge diet. Using multivariate maximum likelihood methods we estimated heritabilities for all 6 traits, genetic and environmental correlations ( G and E ) between them, and the additive genetic variance of each subfraction's response to the diets. On the Chow diet, genetic correlations between the 3 subfractions were significant, and we observed complete pleiotropy between HDL 1 -C and HDL 3 -C ( G ϭϪ0.81). On the HCSF diet, only the genetic correlation between HDL 1 -C and HDL 3 -C ( G ϭϪ0.61) was significant. Genetic correlations between individual subfractions on the Chow and HCSF diets did not differ significantly from 1.0, indicating that the same additive genes influenced each subfraction's levels regardless of diet. However, the additive genetic variance of response to the diets was highly significant for HDL 1 -C and HDL 2 -C, but not for HDL 3 -C. Similar sets of genes influence variation in the 3 HDL subfractions on the Chow diet, and the same set influences variation in each subfraction on the HCSF diet. However, the expression of genes influencing HDL 1 -C and HDL 2 -C is altered by the HCSF diet, disrupting the pleiotropy observed between the 3 subfractions on the Chow diet.

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Genetic differentiation between baboon subspecies: Relevance for biomedical research

Cited by 72 publications

References 25 publications

Two Major Loci Control Variation in β-Lipoprotein Cholesterol and Response to Dietary Fat and Cholesterol in Baboons

Two Major Loci Control Variation in β-Lipoprotein Cholesterol and Response to Dietary Fat and Cholesterol in Baboons

Genetics of leptin expression in baboons

Pleiotropy and Genotype by Diet Interaction in a Baboon Model for Atherosclerosis

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