Study of the genetic transmission of hypercholesterolemia and hypertriglyceridemia in a 195 member kindred

Elston, Robert C.; Namboodiri, K. K.; Glueck, Charles J.; Fallat, R.; Tsang, Reginald C.; Leuba, Victoria

doi:10.1111/j.1469-1809.1975.tb00109.x

Cited by 104 publications

(58 citation statements)

References 17 publications

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“…Each CSA consisted of the evaluation of five different models (50). Model 1 is the null model, in which no genetic effects are estimated (i.e., all elements of m and u 1 are equal to zero) and covariance between relatives is allowed to be explained only by the common vial environment experienced by full siblings.…”

Section: Methodsmentioning

confidence: 99%

Natural selection stops the evolution of male attractiveness

Hine

McGuigan

Blows

2011

Proc. Natl. Acad. Sci. U.S.A.

137

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Sexual selection in natural populations acts on highly heritable traits and tends to be relatively strong, implicating sexual selection as a causal agent in many phenotypic radiations. Sexual selection appears to be ineffectual in promoting phenotypic divergence among contemporary natural populations, however, and there is little evidence from artificial selection experiments that sexual fitness can evolve. Here, we demonstrate that a multivariate male trait preferred by Drosophila serrata females can respond to selection and results in the maintenance of male mating success. The response to selection was associated with a gene of major effect increasing in frequency from 12 to 35% in seven generations. No further response to selection, or increase in frequency of the major gene, was observed between generations 7 and 11, indicating an evolutionary limit had been reached. Genetic analyses excluded both depletion of genetic variation and overdominance as causes of the evolutionary limit. Relaxing artificial selection resulted in the loss of 52% of the selection response after a further five generations, demonstrating that the response under artificial sexual selection was opposed by antagonistic natural selection. We conclude that male D. serrata sexually selected traits, and attractiveness to D. serrata females conferred by these traits, were held at an evolutionary limit by the lack of genetic variation that would allow an increase in sexual fitness while simultaneously maintaining nonsexual fitness. Our results suggest that sexual selection is unlikely to cause divergence among natural populations without a concomitant change in natural selection, a conclusion consistent with observational evidence from natural populations.genetic variance | genetic constraint

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Section: Methodsmentioning

confidence: 99%

Natural selection stops the evolution of male attractiveness

Hine

McGuigan

Blows

2011

Proc. Natl. Acad. Sci. U.S.A.

137

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“…Lynch and Walsh (1998) provide a more complete description of complex segregation analysis. Elston et al (1975) outlined the criteria that must be satisfied before acceptance of the single major locus model so as to reduce the risk of false-positive declarations of a major locus model. Evaluation of the models necessary for complex segregation analysis was conducted with the Bayesian software package iBay (2006, v. 1.0; Janss Biostatistics, Leiden, Netherlands).…”

Section: Genetic Analysismentioning

confidence: 99%

“…Also presented in Table 2, however, are tests of the significance of the Mendelian transmission patterns of this putative major allele. Elston et al (1975) outlined the criteria that must be met for the declaration of a significant major locus in complex segregation analysis. One of these criteria was a test for Mendelian transmission at the putative major locus.…”

Section: Genetical Analysismentioning

confidence: 99%

Hereditary hydrocephalus internus in a laboratory strain of golden hamsters (Mesocricetus auratus)

Gebhardt-Henrich

Edwards

Famula

et al. 2008

Animal

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Golden hamsters of one common laboratory strain had a high incidence of hydrocephalus internus. When a severity score of hydrocephalus was used, a major autosomal recessive locus could be identified. However, when a binary score (hydrocephalus, no hydrocephalus) was used, no such major locus could be detected and results of test matings were not consistent with Mendelian inheritance. Golden hamsters with severe forms of hydrocephalus had a dorsally compressed and ventrally intact hippocampus. Implications for the behavior and well-being of affected hamsters are unknown but researchers using this strain should be aware of the likely presence of hydrocephalus.

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“…23 In contrast, we have taken a population-based approach to examine the distribution of phenotypic data in 4 different race/ethnic groups and the association with prevalence of HFE gene mutations and disease manifestations. Another example of how this approach can be useful is given by Namboodiri et al 24 and Elston et al 25 They analyzed the age-adjusted bivariate distribution of cholesterol and triglycerides in data from 247 individuals in 33 families where the probands had a type IIb lipoprotein phenotype. Results showed that the joint distribution had only 1 local maximum, which suggests the action of a single genetic determinant in the sample.…”

Section: Discussionmentioning

confidence: 99%

“…They discuss the power of bivariate analyses of multigenerational data. 24,25 Limitations of the current study are that TS and SF were based on single determinations of blood samples collected at various times during the day. Considerable day-to-day variation exists for TS, 9 and this measure is also affected by a substantial diurnal variation.…”

Section: Discussionmentioning

confidence: 99%

Bivariate mixture modeling of transferrin saturation and serum ferritin concentration in Asians, African Americans, Hispanics, and whites in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

McLaren

Chen

Barton

et al. 2008

Translational Research

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Bivariate mixture modeling was used to analyze joint population distributions of transferrin saturation (TS) and serum ferritin concentration (SF) measured in the Hemochromatosis andIron Overload Screening (HEIRS) Study. Four components (C1, C2, C3, and C4) with successively age-adjusted increasing means for TS and SF were identified in data from 26,832 African Americans, 12,620 Asians, 12,264 Hispanics, and 43,254 whites. The largest component, C2, had normal mean TS (21% to 26% for women, 29% to 30% for men) and SF (43-82 g/L for women, 165-242 g/L for men), which consisted of component proportions greater than 0.59 for women and greater than 0.68 for men. C3 and C4 had progressively greater mean values for TS and SF with progressively lesser component proportions. C1 had mean TS values less than 16% for women (<20% for men) and SF values less than 28 g/L for women (<47 g/L for men). Compared with C2, adjusted odds of iron deficiency were significantly greater in C1 (14.9-47.5 for women, 60.6-3530 for men), adjusted odds of liver disease were significantly greater in C3 and C4 for African-American women and all men, and adjusted odds of any HFE mutation were increased in C3 (1.4-1.8 for women, 1.2-1.9 for men) and in C4 for Hispanic and white women (1.5 and 5.2, respectively) and men (2.8 and 4.7, respectively). Joint mixture modeling identifies a component with lesser SF and TS at risk for iron deficiency and 2 components with greater SF and TS at risk for liver disease or 97Transferrin saturation (TS) and serum ferritin concentration (SF) are iron measures, the levels of which are influenced by iron stores, a variety of inflammatory and neoplastic disorders, and inheritance of alleles in ironrelated genes. C282Y is a common missense mutation of the HFE gene, 1 which is detected typically in whites of northern European ancestry; however, the HFE H63D allele occurs in most race/ethnic groups worldwide.2 In Caucasian participants enrolled in a screening study conducted at the Kaiser Permanente San Diego Health Appraisal Clinic, components of TS identified by mixture modeling corresponded to distributions of HFE genotypes.3 The Hemochromatosis and Iron Overload Screening (HEIRS) Study is a large, multicenter screening study in which TS, SF, and HFE mutations were measured for each participant.4,5 Analyses of phenotypic and genotypic data collected from 44,136 non-Hispanic Caucasian participants in the HEIRS Study enrolled in different geographic regions demonstrated a strong association between the HFE genotype and the TS subpopulations. The analyses also confirmed the validity of the mixture modeling approach when applied to a convenience sample of patients observed at primary care clinics and at blood drawing facilities. 6 In contrast with previous investigations that modeled the univariate distribution of TS, we now report detailed analyses of the bivariate distribution of TS and SF values from African Americans, Asians, Hispanics, and non-Hispanic whites enrolled in the HEIRS Study.The following hypotheses ...

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Study of the genetic transmission of hypercholesterolemia and hypertriglyceridemia in a 195 member kindred

Cited by 104 publications

References 17 publications

Natural selection stops the evolution of male attractiveness

Natural selection stops the evolution of male attractiveness

Hereditary hydrocephalus internus in a laboratory strain of golden hamsters (Mesocricetus auratus)

Bivariate mixture modeling of transferrin saturation and serum ferritin concentration in Asians, African Americans, Hispanics, and whites in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

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