PubMed Health⌕ Search

Biomedical subjects

C M Kammerer

Publications and source records attributed to C M Kammerer.

52 records · Page 3Linked to original sources
PubMed1991

Linkage of plasminogen (PLG) and apolipoprotein(a) (LPA) in baboons.

Four allelic forms of serum plasminogen (PLG) were detected in baboons (Papio hamadryas Linneaus 1758) by isoelectric focusing and were determined to be inherited as autosomal codominant traits. Linkage analysis of data from 179 progeny and their parents revealed that PLG is tightly linked (lod score = 30.20) to the gene encoding apolipoprotein(a) (LPA), as in humans. No recombinant individuals were identified. This is the first linkage detected between PLG and LPA in any species other than humans and is the first genetic linkage identified in a nonhuman primate species by family studies.

Alleles↗
PubMed1990

Genetic analysis of apolipoprotein A-I in two dietary environments.

Although of great clinical and biological importance, the role of genotype-diet interaction in lipoprotein metabolism and atherosclerosis is still poorly understood. We analyzed serum apolipoprotein A-I (apo A-I) concentrations of approximately 600 pedigreed baboons that were fed two dietary regimens: (1) a basal diet and (2) an atherogenic (high-cholesterol, saturated-fat) diet. Complex segregation analysis was performed separately for apo A-I concentrations in each dietary environment. A major locus model with a recessive allele for high levels of apo A-I and a polygenic component best fit the family data for both diets. Using bivariate segregation analysis, we showed that the major genes detected in the univariate analyses represent two distinct loci that act additively to determine apo A-I concentrations. These two loci accounted for approximately 40% of the total phenotypic variance in apo A-I levels in each dietary environment and were also responsible for 33% of the variation in apo A-I response to the atherogenic diet. Both major loci were influenced by genotype-diet interaction in which the two-locus genotypes exhibited heterogeneous responses to the atherogenic diet. Most genotypes responded to the atherogenic diet with an increase in apo A-I, but two genotypes showed a decrease that can be traced to the effect of one of the major loci. The presence of two major loci and genotype-diet interaction may be responsible for the equivocal results obtained in human pedigree studies of apo A-I.

Animals↗
PubMed1989

Segregation analysis of quantitative traits in nuclear families: comparison of three program packages.

Segregation analysis frequently is used to test for the presence of major gene effects and to estimate the various genetic and environmental components contributing to diseases. Recent advances in both theoretical models and computational algorithms have provided a number of new programs for performing segregation analyses. We compared two newer programs: REGC (part of the package "SAGE") and FISHER/MENDEL with an older established program (PAP) to determine relative accuracy in recovering parameter values and asymptotic standard errors, ability to discriminate between alternative transmission models, and execution speeds. Each program was applied to a set of computer simulations of a quantitative trait generated under a variety of genetic models. The results of these comparisons indicated that all the programs provided very similar parameter estimates, but that they differed in their abilities to identify the correct mode of transmission. In our simulations, PAP more often led to the selection of the correct transmission model, whereas REGC frequently indicated the presence of a major gene in simulations of purely polygenic transmission. Relative speeds for the programs differed, and their rank ordering varied with the complexity of the model being fitted. Although REGC was the fastest program for fitting a major gene or mixed model, it was by far the slowest program for estimating parameters in a sporadic or polygenic model.

Computer Simulation↗
PubMed1988

Method for quantitating cholesterol in subfractions of serum lipoproteins separated by gradient gel electrophoresis.

Extensive heterogeneity in particle size distribution of serum lipoproteins of baboons was resolved by a procedure that combined Sudan black B prestaining, polyacrylamide gradient gel electrophoresis (GGE), and quantitative densitometry. Each densitometric scan represented a continuous distribution of the relative amount of cholesterol in a serum sample, as a function of the lipoprotein particle size. For analytical purposes, each scan was divided into 12 fractions, representing 12 particle size ranges. The relationship between the estimated cholesterol concentrations in the summed GGE/densitometric fractions corresponding to very low-density lipoproteins (VLDL) + low-density lipoproteins (LDL) and those corresponding to high-density lipoproteins (HDL) and concentrations measured by the heparin-Mn2+ precipitation/enzymatic procedure was linear over a broad range. However, a systematic overestimation of HDL cholesterol concentration and an underestimation of VLDL + LDL cholesterol concentration was apparent. Therefore, correction factors were developed for adjusting the estimates of VLDL + LDL and HDL cholesterol concentrations obtained by the GGE/densitometric method. This analytical method is rapid, repeatable, economical, and useful for genetic and dietary research in which cholesterol concentrations in multiple particle size ranges of lipoproteins must be measured in large numbers of samples. It also is adaptable to immunoblotting procedures for detecting the distribution of specific apolipoproteins among the size-resolved lipoproteins.

Centrifugation, Density Gradient↗
PubMed1988

Pedigree analysis of HDL cholesterol concentration in baboons on two diets.

Using complex segregation analysis, we examined the effects of genetic factors and diet on serum concentrations of high-density-lipoprotein cholesterol (HDL-C) in baboons. In analyses of 710 baboons in 23 sire families, we found evidence for a major gene as well as a polygenic contribution to HDL-C concentration in baboons fed a basal (chow) diet and also in the same animals after challenge with a high-cholesterol, saturated-fat diet. There was evidence for a polygenic contribution to the change in HDL-C concentration in response to the dietary challenge, but there was no evidence for a major gene effect.

Animals↗
PubMed1988

Empirical power of three preliminary methods for ordering loci.

We empirically estimated the power of three methods for ordering loci within a known linkage group. Estimates of pairwise recombination fractions and correlation coefficients were obtained from data on 50 replicates of 50 and 100 pedigrees by using a likelihood method (LIPED; Ott 1974) and the sib-pair test. Locus order then was determined using seriation, multidimensional scaling, and the product of recombination frequencies. Overall, the multidimensional scaling method was less powerful than either seriation or the product of recombination frequencies. The latter two methods were approximately equally powerful. As expected, the power of the sib-pair test was less than half that of the likelihood method.

Chromosome Mapping↗
PubMed1987

Detecting genetic effects on lipoprotein phenotypes in baboons: a review of methods and preliminary findings.

Statistical methods for detecting the contribution of major genes to quantitative phenotypes have been widely applied in human family studies. Some of these methods are reviewed, and their application to analysis of an animal model for a human disease is described. Analysis of lipoprotein concentrations in pedigreed baboons provides evidence for genetic effects on specific lipoprotein components that have been associated with reduced susceptibility to atherosclerosis in humans.

Animals↗
PubMed1985

Comparison of two preliminary methods of quantitative linkage analysis.

Two methods of quantitative linkage analysis were evaluated as screening tests for the presence of major genes that influence the expression of a quantitative trait. Our analyses of computer-simulated pedigree data indicate that both methods can be very informative in providing evidence for major genes.

Computers↗
PubMed1984

Effects of selection for serum cholesterol concentrations on serum lipid concentrations and body weight in baboons.

We examined the results of one generation of selection for serum cholesterol (SC) concentration on low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglyceride concentrations and weight in baboons (Papio cynocephalus). Parents of two lines (high SC response and low SC response) were chosen based on their SC response to a 4-month challenge with a cholesterol and saturated fat enriched diet. Parents of the control line were chosen without regard for SC levels. Expression of SC, LDL-C, and HDL-C concentrations was moderately influenced by additive genetic effects as evidenced by the direct and correlated responses of the serum lipoprotein concentrations of the juvenile offspring of the three lines. Realized heritability of SC and genetic correlations of SC with LDL-C and HDL-C were moderate to high. Sex and age were important factors influencing expression of SC, LDL-C, HDL-C, triglycerides, and weight in both adult baboons and their offspring.

Animals↗
PubMed1984

Acetazolamide and cerebral oxygenation in dogs.

Acetazolamide could theoretically impair oxygen delivery to cerebral tissue by inhibiting local acidification of capillary blood. There is considerable evidence, however, that acetazolamide improves cerebral oxygen tension. This experiment was designed to demonstrate increased deep cerebral oxygen tension after acetazolamide. Three groups of dogs were anesthetized with pentobarbital and ventilated with a respirator. A Teflon-coated stainless steel catheter was placed through a craniotomy into the parietal lobe and advanced into the corona radiata to monitor cerebral pO2 and pCO2 with a mass spectrometer. Group one dogs were normoxic and eucapneic. Group two dogs were hypoxemic, and Group three dogs were hypocapneic. After control cerebral and arterial gas tensions had been recorded, acetazolamide (30 mg kg-1) was injected intravenously. Cerebral gas tensions were monitored continuously and arterial gases were analyzed at 30, 60, 90 and 120 min. Cerebral oxygen tension was not decreased by acetazolamide in any of the dogs. Cerebral carbon dioxide tension was increased by acetazolamide in all dogs. We conclude that acetazolamide does not deplete cerebral oxygen tension even in the face of hypoxemia or acute hypocapnea.

Acetazolamide↗
PubMed1984

An evaluation of three statistics of structured exploratory data analysis.

The power of structured exploratory data analysis (SEDA) to discriminate among major genic, polygenic, and nongenetic determination of phenotypes was investigated using computer simulation. Three classes of SEDA indices (the major gene index, the offspring between parents function, and the midparent-child correlation coefficient) were evaluated. These three statistics, in combination, were reasonably sensitive in detecting the presence of a major locus and in discriminating between phenotypes with genetic effects and those with no genetic component. However, they were unable to discriminate between major genic and polygenically determined phenotypic models.

Chromosome Mapping↗
PubMed1984

Structured exploratory data analysis: an evaluation of the use of three SEDA statistics in assessing mode of inheritance.

Several SEDA statistics are described and three of them (the Midparent-Child Correlation Coefficient, the Major Gene Index, and the Offspring Between Parents Function) are evaluated with respect to their ability to distinguish monogenic, polygenic and sporadic effects on quantitative traits. The MPCC, MGI, and OBP, used in combination, are sensitive but not specific in identifying monogenic inheritance. In our tests, traits determined by a simple type of polygenic inheritance were almost invariably classified as monogenic. Sporadic traits, on the other hand, were correctly identified in 84 percent of cases. The concurrent use of these SEDA statistics and two sibship variance tests yielded some improvement whenever the two procedures agreed (which happened about 50 percent of the time). These results suggest that under some circumstances, SEDA can be a valuable adjunct to other methods of genetic analysis. SEDA methodology also appears promising as an aid in understanding the contribution of various nongenetic factors to quantitative traits.

Female↗
PubMedDate not supplied

Identification of LDL receptor gene marker associated with altered levels of LDL cholesterol and apolipoprotein B in baboons.

We are studying the genetic factors underlying the common forms of heart disease by identifying genes that affect normal variations in plasma lipid, lipoprotein, and apolipoprotein concentrations in baboons. For these studies we are using cloned human gene probes to identify restriction fragment length polymorphisms (RFLPs) at loci encoding the proteins of cholesterol metabolism. In this report we present the identification and mapping of a polymorphic Ava II cleavage site in intron 17 of the baboon low density lipoprotein (LDL) receptor gene. We determined genotypes for this RFLP on a population of 253 pedigreed baboons and assessed the effect of LDL receptor RFLP genotypes on serum concentrations of LDL cholesterol (LDL-C) and apolipoprotein B (apo B). These measures were obtained for each baboon on each of two diets: a low cholesterol, low fat (basal) diet and a high cholesterol, high saturated fat (atherogenic) diet. Statistical analysis detected a significant association between LDL receptor genotype and serum LDL-C and apo B concentrations on both diets. Homozygotes for the rarer allele had lower serum concentrations of LDL-C and apo B than did homozygotes for the common allele, and with the exception of apo B levels on the basal diet, intermediate levels were observed in heterozygotes. The LDL receptor RFLP accounted for approximately 3% to 7% of the variation in serum LDL-C and apo B concentrations on both diets.

Analysis of Variance↗
PubMedDate not supplied

Lipoprotein Lp(a): effects of allelic variation at the LPA locus.

Concentrations of the lipoprotein Lp(a) vary widely in healthy individuals, but in many studies, high concentrations are strongly associated with cardiovascular disease. On the basis of lipid and protein composition, Lp(a) is a variant of the atherogenic low-density lipoprotein but differs in possessing the unique apolipoprotein(a) [apo(a)]. Lp(a) concentrations are controlled at the level of biosynthesis of the apo(a) protein, which is encoded by the LPA locus, and allelic differences at LPA are responsible for the bulk of variation in Lp(a) phenotype. In this article we describe several aspects of allelic variation at LPA reported in studies of human and baboons, including (1) polymorphisms for protein size, (2) families of alleles having distinct relationships between apo(a) size and Lp(a) concentration, (3) sequence polymorphisms, (4) a group of alleles whose protein products have a multibanded phenotype, and (5) allelic diversity of null phenotype alleles (whose protein products are not detected in the plasma). The data make clear that no single aspect of allelic variation at LPA is sufficient to fully explain the genetic control of Lp(a).

Alleles↗