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PubMed2005

The power to detect genetic linkage for quantitative traits in the Utah CEPH pedigrees.

Quantitative trait phenotypes and linked marker genotypes were simulated for a range of models with different sets of assumptions based on displacement, prevalence, and heritability of the trait in 30 Utah Centre d'Etude du Polymorphisme Humain (CEPH) families. The gain in power by the addition of 15 families was also estimated by extrapolation. Power was evaluated using both parametric single locus (PSL) models and variance components (VC) methods for two situations: (1) a single marker with 75% heterozygosity and a recombination fraction of 0.05, and (2) a fully informative marker as an approximation to multipoint analysis. When the simulation and analysis models were both dominant with the same prevalence, power > or =80% for lod >3 was estimated when quantitative trait locus variance was > or =40% with a displacement of 2.5 or 3. Power was 5-15% lower for recessive models compared to dominant models. With the addition of 15 families, an average increase in power of 17% and 22% was estimated for the dominant and recessive models, respectively. In PSL analyses, power was estimated at < or =20% when the dominance was misspecified. This investigation delineates parameter conditions under which this unique sample affords adequate power to detect linkage using both PSL and VC methods.

Genetic Linkage↗
PubMed1991

Quantitative analysis of genetic differentiation among European and Chilean strains of Drosophila subobscura.

An analysis of the interpopulational differences observed between four European and four Chilean stocks of Drosophila subobscura, with regard to wing size, egg-to-adult development time and preadult viability, shows highly significant differences between the eight stocks irrespective of the continent from which the flies are derived. The divergence of the local populations with regard to the quantitative traits described here, supplements other evidence of interpopulational differences in mating activity, chromosomal and enzyme polymorphisms. These together indicate that the evolutionary process that promotes race formation is relatively rapid, bearing in mind that D. subobscura was detected for the first time in South America in 1978.

Animals↗
PubMed1996

Genetic mapping of quantitative trait loci controlling growth and wood quality traits in Eucalyptus grandis using a maternal half-sib family and RAPD markers.

Quantitative trait loci (QTL) mapping of forest productivity traits was performed using an open pollinated half-sib family of Eucalyptus grandis. For volume growth, a sequential QTL mapping approach was applied using bulk segregant analysis (BSA), selective genotyping (SG) and cosegregation analysis (CSA). Despite the low heritability of this trait and the heterogeneous genetic background employed for mapping, BSA detected one putative QTL and SG two out of the three later found by CSA. The three putative QTL for volume growth were found to control 13.7% of the phenotypic variation, corresponding to an estimated 43.7% of the genetic variation. For wood specific gravity five QTL were identified controlling 24.7% of the phenotypic variation corresponding to 49% of the genetic variation. Overlapping QTL for CBH, WSG and percentage dry weight of bark were observed. A significant case of digenic epistasis was found, involving unlinked QTL for volume. Our results demonstrate the applicability of the within half-sib design for QTL mapping in forest trees and indicate the existence of major genes involved in the expression of economically important traits related to forest productivity in Eucalyptus grandis. These findings have important implications for marker-assisted tree breeding.

Chromosome Mapping↗
PubMed2005

Quantitative analysis of genetic and neuronal multi-perturbation experiments.

Perturbation studies, in which functional performance is measured after deletion, mutation, or lesion of elements of a biological system, have been traditionally employed in many fields in biology. The vast majority of these studies have been qualitative and have employed single perturbations, often resulting in little phenotypic effect. Recently, newly emerging experimental techniques have allowed researchers to carry out concomitant multi-perturbations and to uncover the causal functional contributions of system elements. This study presents a rigorous and quantitative multi-perturbation analysis of gene knockout and neuronal ablation experiments. In both cases, a quantification of the elements' contributions, and new insights and predictions, are provided. Multi-perturbation analysis has a potentially wide range of applications and is gradually becoming an essential tool in biology.

Algorithms↗
PubMed1984

The genetic analysis of quantitative trait differences between two homozygous lines.

Previous maximum likelihood methods to analyze quantitative data on two inbred parental strains, their F1 and backcross generations are extended in three directions: (1) a method is suggested to transform the data to better satisfy the assumptions of normality and homoscedasticity; (2) the likelihoods are modified to allow for litter correlations and heteroscedasticity and (3) allowance is made for the incorporation of F2 data. The problem of making a choice among a set of simple genetic hypotheses is further discussed.

Crosses, Genetic↗
PubMed1995

Multiple trait analysis of genetic mapping for quantitative trait loci.

We present in this paper models and statistical methods for performing multiple trait analysis on mapping quantitative trait loci (QTL) based on the composite interval mapping method. By taking into account the correlated structure of multiple traits, this joint analysis has several advantages, compared with separate analyses, for mapping QTL, including the expected improvement on the statistical power of the test for QTL and on the precision of parameter estimation. Also this joint analysis provides formal procedures to test a number of biologically interesting hypotheses concerning the nature of genetic correlations between different traits. Among the testing procedures considered are those for joint mapping, pleiotropy, QTL by environment interaction, and pleiotropy vs. close linkage. The test of pleiotropy (one pleiotropic QTL at a genome position) vs. close linkage (multiple nearby nonpleiotropic QTL) can have important implications for our understanding of the nature of genetic correlations between different traits in certain regions of a genome and also for practical applications in animal and plant breeding because one of the major goals in breeding is to break unfavorable linkage. Results of extensive simulation studies are presented to illustrate various properties of the analyses.

Algorithms↗
PubMed2000

ApoE polymorphism accounts for only part of the genetic variation in quantitative ApoE levels.

ApoE levels and chromosome 19 ApoE polymorphisms were measured in a sample of 156 Dutch families. Each pedigree consisted of parents aged 35-65 years and their twin offspring aged 14-21 years. A significant effect of the chromosome 19 apoE locus on quantitative plasma levels of apolipoprotein E was observed. The ApoE polymorphism explained 16% of the variance in ApoE levels. Tests of association of ApoE levels with the apoC1 locus, which is in complete linkage disequilibrium with the ApoE locus, also showed a significant effect, although the variance explained by ApoC1 was only 1%. Examination of the covariance between twins classified according to allele sharing indicates that the association is not due to population stratification, but to a genuine effect of the ApoE locus on levels. However, the ApoE locus accounts for only one-fourth of the genetic variation in ApoE levels.

Adolescent↗
PubMed1981

Estimation of environmental and genetic components of quantitative traits with application to serum cholesterol levels.

A mixed model of environmental, polygenic, and major locus effects is developed, allowing for environmental correlations between first-degree relatives and spouses. Maximum-likelihood techniques are used to determine the relative contributions of each of these effects to a quantitative trait. Inclusion of a nuclear family in the sample is assumed to depend on the value of the quantitative trait of one member of the family, so conditional distributions are used. Application of the method to serum cholesterol data from the general population shows that the addition of a polygenic effect to a model that assumes only an environmental effect makes a significant improvement. A completely dominant single gene is also found to be influencing serum cholesterol levels. Although cholesterol levels have been adjusted for a range of factors, such as age, sex, weight/height, and marital status, environmental factors still account for about half the variability in the residual values.

Adult↗
PubMed2006

Mapping QTL for biomass yield and its components in rice (Oryza sativa L.).

Additive effects, additive by additive epistatic effects, and their environmental interactions of QTLs are important genetic components of quantitative traits. Genetic architecture underlying rice biomass yield and its two component traits (straw yield and grain yield) were analyzed for a population of 125 DH lines from an inter-subspecific cross of IR64/Azucena. The mixed-model based composite interval mapping approach (MCIM) was used to detect QTLs, There were 12 QTLs detected with additive main effects, 27 QTLs involved in digenic interaction with aa and/or aae effects, and 18 QTLs affected by environments with ae and/or aae effects. It was revealed that epistatic effects and QE interaction effects existed on biomass yield and its component traits in rice. In addition, the genetic basis of relationships among these traits were investigated. Four QTLs and one pair of epistatic QTLs were detected to be responsible for the positive correlation between biomass yield and straw yield. Three QTLs might be responsible for the negative correlation between straw yield and grain yield. This result could partially explain the genetic basis of correlation among the three traits, and provide useful information for genetic improvement of these traits by marker-assisted selection.

Biomass↗
PubMed1993

Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease: analysis of a large pedigree from the Bogalusa Heart Study.

A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI x LDL-C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL-C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the ratio apoAI/HDL-C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease.

Apolipoproteins↗
PubMed1984

Genetic effects on quantitative variation in serologically detected H-Y antigen.

We have examined effects of an autosomal gene on the expression of serologically detectable H-Y, a male-specific minor histocompatibility antigen for which a role in primary sex determination has been postulated. Quantitative immunoabsorption studies using three different male specific antisera revealed variation in the level of H-Y among inbred mouse strains and mice bearing variants of the T/t complex. Two patterns of expression in inbred strains were observed; high, C57BL/6J (B6) and low, which included A/J (A), C3H/ DiSn and DBA/2J. In F1 hybrids between A (female parent) and B6 (male parent), the F1 expressed H-Y levels indistinguishable from A, the low parent. Among T/t complex variants, mice bearing T or t0 showed high expression whereas those of the t12 haplotype showed low expression. The co-segregation of H-Y expression types with these T/t complex variants provided further evidence for the location of a gene determining the level of H-Y antigen on the proximal portion of chromosome 17.

Animals↗
PubMed1977

Genetic control of quantitative variation in carbonic anhydrase isozymes of mammals. I. The concentration within single erythrocytes of the mouse.

The levels of the carbonic anhydrase isozymes (CA and CA II) in single erythrocytes of DBA/2J mice were assayed by measuring the specific immunofluorescence of CA I and CA II with a microspectrofluorometric technique. Measurements of 100 randomly selected cells showed a range (in relative fluorescence units) of 21-52 (mean 31.3 +/- 7.5) for CA I and 30-80 (mean 45.6 +/- 10.7) for CA II. The CA II/CA I ratio of the means obtained by the single-cell fluorescence assay was similar to the ratios obtained for the two isozymes from hemolysates of DBA/2J mice using an immunodiffusion assay. The influence of cell age on the variation in carbonic anhydrase levels was determined by separating red cells into several fractions by a gravity sedimentation procedure. The younger cells showed higher levels of CA I and CA II than the older cells; however, the extensive overlap in the variability between the cells from the different fractions indicated that although cell age was contributing to the overall heterogeneity, its influence was not pronounced.

Animals↗
PubMed1981

Genetic analysis of quantitative characters in cigar and pipe tobacco Nicotiana tabacum II. Grades of cigar filler tobacco.

A diallel cross of four cigar and one pipe tobacco (Nicotiana tabacum L.) was analyzed for the following characters in samples of cured tobacco: (1) percentage of light filler; (2) percentage of heavy filler; (3) percentage of top filler; (4) percentage of bottom filler; (5) percentage of total filler; (6) percentage of marketable trash and (7) total percentage of marketable tobacco. The experiment was performed over three years with four replications. Analysis was done for general combining ability and specific combining ability. General combining ability was greater than specific combining ability for all parameters, although specific combining ability effects were also present for all parameters with the exception of total marketable tobacco. Reciprocal effects were completely absent. The line Pennbel 69 showed a negative general combining ability effect for all grades of filler, total filler and total marketable tobacco with a positive effect for percentage of marketable trash. High positive specific combining ability effects for percentage total filler and high negative specific combining ability effects for percentage marketable trash were shown by crosses of Pennbel 69 with the other four cultivars.

Plants↗
PubMed1975

Genetic aspects of quantitative variation in the carbonic anhydrases of the pig-tailed macaque, Macaca nemestrina. I. Response to thyroxine.

Effects of thyroxine on incorporation of L-serine-C14 into four carbonic anhydrase isozymes (CA II, CA Ia, CA Ib, CA Ic) and hemoglobin were quantified in reticulocytes of Macaca nemestrian in vitro. Response to thyroxine differed significantly between CA Ia and two allelic variants (CA Ib and CA Ic) and the nonallelic isozyme (CA II). The effects of thyroxine on serine incorporation into hemoglobin and three of the carbonic anhydrase isozymes were shown to be nonlinear with thyroxine concentration.

Alleles↗
PubMed2005

Quantitative evaluation of genetic and environmental parameters determining antibody response induced by vaccination against bovine respiratory syncytial virus.

The parameters controlling IgG antibody responses induced by vaccination against bovine respiratory syncytial virus (BRSV) were investigated in 463 Holstein-Charolais crossbred cattle. Pre- and post-vaccination sera were tested by enzyme linked immunosorbent assays (ELISA) for BRSV-specific IgG and IgG2. Year-of-birth, age, sex and pre-existing antibody were significant sources of variation for IgG responses. Pre-vaccination, progeny with a higher proportion of Holstein genes had higher total BRSV-IgG. By Day 35 post-vaccination, heritabilities peaked at 0.26 for total BRSV-IgG and 0.36 for BRSV-IgG1. There was no evidence for interbreed differences between Holstein and Charolais calves, post-vaccination. These results suggest that calf-sire has a major heritable influence on serum IgG levels following BRSV immunisation.

Aging↗