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At least 865 records · Page 48Linked to original sources
PubMed1999

Linkage analysis of molecular markers and quantitative trait loci in populations of inbred backcross lines of Brassica napus L.

Backcross populations are often used to study quantitative trait loci (QTL) after they are initially discovered in balanced populations, such as F(2), BC(1), or recombinant inbreds. While the latter are more powerful for mapping marker loci, the former have the reduced background genetic variation necessary for more precise estimation of QTL effects. Many populations of inbred backcross lines (IBLs) have been developed in plant and animal systems to permit simultaneous study and dissection of quantitative genetic variation introgressed from one source to another. Such populations have a genetic structure that can be used for linkage estimation and discovery of QTL. In this study, four populations of IBLs of oilseed Brassica napus were developed and analyzed to map genomic regions from the donor parent (a winter-type cultivar) that affect agronomic traits in spring-type inbreds and hybrids. Restriction fragment length polymorphisms (RFLPs) identified among the IBLs were used to calculate two-point recombination fractions and LOD scores through grid searches. This information allowed the enrichment of a composite genetic map of B. napus with 72 new RFLP loci. The selfed and hybrid progenies of the IBLs were evaluated during two growing seasons for several agronomic traits. Both pedigree structure and map information were incorporated into the QTL analysis by using a regression approach. The number of QTL detected for each trait and the number of effective factors calculated by using biometrical methods were of similar magnitude. Populations of IBLs were shown to be valuable for both marker mapping and QTL analysis.

Brassica↗
PubMed2006

Characterization of Cq3, a quantitative trait locus that controls plasma cholesterol and phospholipid levels in mice.

Cq3 was identified in C57BL/6J (B6) x KK-Ay F2 mice as a quantitative trait locus (QTL) that controls plasma cholesterol and phospholipid levels, and normolipidemic B6 allele was associated with increased lipids. Cq3 was statistically significant in F2-a/a, but not in F2-Ay/a; probably because the Cq3 effect was obscured by introduction of the Ay allele, which in itself has a strong hyperlipidemic effect. Because the peak LOD score for Cq3 was identified near D3Mit102 (49.7 cM) on chromosome 3, linkage analyses with microsatellite markers located at 49.7 cM were performed in KK x RR F2, B6 x RR F2, and KK x CF1 F2. However, even a suggestive QTL was not identified in any of the three F2. By testing all pairs of marker loci, I found a significant interaction between Cq3 and the Apoa2 locus, and F2 mice with the Apoa2(KK)/Apoa2(KK); D3Mit102(B6)/D3Mit102(B6) genotype had significantly higher cholesterol levels than did F2 mice with other genotypes. The results showed that the ;round-robin' strategy was not always applicable to the search for QTL genes; probably because specific gene-to-gene interaction limited the validity of the strategy to the utmost extent.

Alleles↗
PubMed2005

Improving quantitative trait loci mapping resolution in experimental crosses by the use of genotypically selected samples.

One of the key factors contributing to the success of a quantitative trait locus (QTL) mapping experiment is the precision with which QTL positions can be estimated. We show, using simulations, that QTL mapping precision for an experimental cross can be increased by the use of a genotypically selected sample of individuals rather than an unselected sample of the same size. Selection is performed using a previously described method that optimizes the complementarity of the crossover sites within the sample. Although the increase in precision is accompanied by a decrease in QTL detection power at markers distant from QTL, only a modest increase in marker density is needed to obtain equivalent power over the whole map. Selected samples also show a slight reduction in the number of false-positive QTL. We find that two features of selected samples independently contribute to these effects: an increase in the number of crossover sites and increased evenness in crossover spacing. We provide an empirical formula for crossover enrichment in selected samples that is useful in experimental design and data analysis. For QTL studies in which the phenotyping is more of a limiting factor than the generation of individuals and the scoring of genotypes, selective sampling is an attractive strategy for increasing genome-wide QTL map resolution.

Chromosome Mapping↗
PubMed2005

Estimation of quantitative trait loci parameters for milk production traits in German Holstein dairy cattle population.

The main objective of this study was to estimate the proportion of total genetic variance attributed to a quantitative trait locus (QTL) on Bos taurus autosome 6 (BTA6) for milk production traits in the German Holstein dairy cattle population. The analyzed chromosomal region on BTA6 spanned approximately 70 cM, and contained 6 microsatellite markers. Milk production data were obtained from routine genetic evaluation for 4500 genotyped German Holstein bulls. Technical aspects related to the estimation of model parameters for a large data set from routine genotype recording were outlined. A fixed QTL model and a random QTL model were introduced to incorporate marker information into parameter estimation and genetic evaluation. Estimated QTL variances, expressed as the ratio of QTL to polygenic variances, were 0.04, 0.03, and 0.07 for milk yield; 0.06, 0.08, and 0.14 for fat yield; and 0.04, 0.04, and 0.11 for protein yield, in the first 3 parities, respectively. The estimated QTL positions, expressed as distances from the leftmost marker DIK82, were 18, 31, and 17 cM for milk yield; 25, 17, and 9 cM for fat yield; and 16, 30, and 17 cM for protein yield in the 3 respective parities. Because the data for the parameter estimation well represented the current population of active German Holstein bulls, the QTL parameter estimates have been used in routine marker-assisted genetic evaluation for German Holsteins.

Analysis of Variance↗
PubMed1998

Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW x C57BL/6)F1 mice.

In the present study, we mapped the major quantitative trait loci (QTL) differing between the NZW and C57BL/6 inbred strains of mice by making use of (NZW x C57BL/6.Yaa)F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa. Linkage analysis of 126 C57BL/6 x (NZW x C57BL/6.Yaa)F1 backcross males provided evidence for a major QTL on chromosome 7 controlling both the severity of glomerulonephritis and the production of IgG anti-DNA autoantibody and retroviral gp70-anti-gp70 immune complexes. Two additional QTL of C57BL/6 origin on chromosome 17 had no apparent individual effects, but showed strong epistatic interaction with chromosome 7 QTL for disease severity and anti-DNA autoantibody production. Our data also identified on chromosome 13 a QTL of NZW origin with a major effect on the level of gp70, and showing an additive effect with the chromosome 7 QTL on the level of gp70 immune complexes. Our study thus provides a model to dissect the complex genetic interactions that result in manifestations of murine lupus-like disease.

Animals↗
PubMed2004

[Identification of quantitative trait loci controlling plant height and days to heading from Yuanjiang common wild rice (Oryza rufipogon Griff.)].

An advanced backcross strategy was used to identify quantitative trait loci (QTLs) associated with plant height and days to heading in the BC3F2 population derived from an accession of common wild rice (Oryza rufipogon Griff.) from Yuanjiang in Yunnan Province of China, as the donor, and an elite Indica cultivar "Teqing", as the recipient. Based on analyses of 116 SSR markers distributed throughout the rice genome and by using single-point analysis, four putative QTLs derived from O. rufipogon were detected for plant height on chromosome 1, and 6 QTLs for days to heading on chromosome 1, 3, 7, 8 and 11. All Alleles of QTLs for plant height from O. rufipogon could increase plant height of the backcross population. One QTL near RM104 on chromosome 1, explaining 27% and 28% of phenotypic variance and additive value reached 26.24 cm and 26.28 cm respectively in Beijing and Hefei, was detected. The location of this QTL is corresponding to sd-1. One QTL near the marker RM25 on chromosome 1, explaining 13% and 15% of phenotypic variance was identified. The additive value of this QTL reached 4.60 days and 3.65 days respectively in Beijing and Hefei, and the allele from O. rufipogon could delay the backcross population's days to heading.

Oryza↗
PubMed2005

Identification of candidate genes at quantitative trait loci on chicken chromosome Z using orthologous comparison of chicken, mouse, and human genomes.

This study was undertaken to identify novel candidate genes at quantitative trait loci (QTL) on chicken chromosome Z (GGAZ) by comparing orthologous regions of chicken, human and mouse genomes. Primer sequences from marker flanking QTL positions (https://acedb.asg.wur.nl/) were obtained from www.iastate.edu/chickmap and blasted against the chicken genome (www.ensembl.org) using BLASTN. The best matches were those with the highest score, lowest E-values and highest percent identity. Orthologous regions in mice and humans, together with genes located on or around those loci were identified using the Ensembl website. Forty-six chicken genes, 91 mouse genes and 60 human genes associated with QTL on GGAZ were identified in the current study. Among the most promising candidate genes for egg production and egg shell quality are annexin A1 (ANXA1), osteoclast stimulating factor (OSF), thrombospondin-4 (THBS4), programmed cell death proteins (PDCD), follistatin (FST), growth hormone receptor (GHR), interferon (IFN) alpha and beta. The chicken IFN alpha and beta were located on GGAZ around position 13,000,000 bp on the draft chicken sequence map. The neuronal nicotinic acetylcholine receptor (nAChR) is located at a QTL region for abdominal fat (GGAZ 25483091 bp). Nicotine is an agonist at the nAChRs and has been shown to decrease lipolysis and triglyceride uptake, thereby reducing net storage in adipose tissue. Therefore, the nAchRs could be used as therapeutic targets for regulating feed intake and obesity. This study has identified 197 putative candidate genes in probable QTL regions of chicken chromosome Z.

Animals↗
PubMed2005

High-resolution association mapping of quantitative trait loci: a population-based approach.

In this article, population-based regression models are proposed for high-resolution linkage disequilibrium mapping of quantitative trait loci (QTL). Two regression models, the "genotype effect model" and the "additive effect model," are proposed to model the association between the markers and the trait locus. The marker can be either diallelic or multiallelic. If only one marker is used, the method is similar to a classical setting by Nielsen and Weir, and the additive effect model is equivalent to the haplotype trend regression (HTR) method by Zaykin et al. If two/multiple marker data with phase ambiguity are used in the analysis, the proposed models can be used to analyze the data directly. By analytical formulas, we show that the genotype effect model can be used to model the additive and dominance effects simultaneously; the additive effect model takes care of the additive effect only. On the basis of the two models, F-test statistics are proposed to test association between the QTL and markers. By a simulation study, we show that the two models have reasonable type I error rates for a data set of moderate sample size. The noncentrality parameter approximations of F-test statistics are derived to make power calculation and comparison. By a simulation study, it is found that the noncentrality parameter approximations of F-test statistics work very well. Using the noncentrality parameter approximations, we compare the power of the two models with that of the HTR. In addition, a simulation study is performed to make a comparison on the basis of the haplotype frequencies of 10 SNPs of angiotensin-1 converting enzyme (ACE) genes.

Alleles↗
PubMed2006

Fine mapping of collagen-induced arthritis quantitative trait loci in an advanced intercross line.

The generation of advanced intercross lines (AIL) is a powerful approach for high-resolution fine mapping of quantitative trait loci (QTLs), because they accumulate much more recombination events compared with conventional F2 intercross and N2 backcross. However, the application of this approach is severely hampered by the requirements of excessive resources to maintain such crosses, i.e., in terms of animal care, space, and time. Therefore, in this study, we produced an AIL to fine map collagen-induced arthritis (CIA) QTLs using comparatively limited resources. We used only 308 (DBA/1 x FVB/N)F11/12 AIL mice to refine QTLs controlling the severity and onset of arthritis as well as the Ab response and T cell subset in CIA, namely Cia2, Cia27, and Trmq3. These QTLs were originally identified in (DBA/1 x FVB/N)F2 progeny. The confidence intervals of the three QTLs were refined from 40, 43, and 48 Mb to 12, 4.1, and 12 Mb, respectively. The data were complemented by the use of another QTL fine-mapping approach, haplotype analysis, to further refine Cia2 into a 2-Mb genomic region. To aid in the search for candidate genes for the QTLs, genome-wide expression profiling was performed to identify strain-specific differentially expressed genes within the confidence intervals. Of the 1396 strain-specific differentially expressed genes, 3, 3, and 12 genes were within the support intervals of the Cia2, Cia27, and Trmq3, respectively. In addition, this study revealed that Cia27 and Trmq3 controlling anti-CII IgG2a Ab and CD4:CD8 T cell ratio, respectively, also regulated CIA clinical phenotypes.

Animals↗
PubMed2000

Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences.

Rat Chromosome 10 (RNO10) harbors Cia5, a non-MHC quantitative trait locus (QTL) that regulates the severity of type II collagen-induced arthritis (CIA) in DAxF344 and DAxBN F2 rats. CIA is an animal model with many features that resemble rheumatoid arthritis. To facilitate analysis of Cia5 independently of the other CIA regulatory loci on other chromosomes, DA recombinant QTL speed congenic rats, DA.F344(Cia5), were generated. These QTL congenic rats have a large chromosomal segment containing Cia5 (interval size < or =80.1 cM) from CIA-resistant F344 rats introgressed into their genome. Phenotypic analyses of these rats for susceptibility and severity of CIA confirmed that Cia5 is an important disease-modifying locus. CIA severity was significantly lower in the Cia5 congenic rats than in DA controls. We also generated DA Cia5 speed sub-congenic rats, DA.F344(Cia5a), which had a smaller segment of the F344 genome, Cia5a, comprising only the distal q-telomeric end (interval size < or = 22.5 cM) of Cia5, introgressed into their genome. DA.F344(Cia5a) sub-congenic rats also exhibited reduced CIA disease severity compared with the parental DA rats. The regulatory effects in both congenic strains were sex influenced. The disease-ameliorating effect of the larger fragment, Cia5, was greater in males than in females, but the effect of the smaller fragment, Cia5a, was greater in females. We also present an improved genetic linkage map covering the Cia5/Cia5a region, which we have integrated with two rat radiation hybrid maps. Comparative homology analysis of this genomic region with mouse and human chromosomes was also undertaken. Regulatory loci for multiple autoimmune/inflammatory diseases in rats (RNO10), mice (MMU11), and humans (HSA17 and HSA5q23-q31) map to chromosomal segments homologous to Cia5 and Cia5a.

Animals↗
PubMed2002

Analysis of genetic effects of major genes and polygenes on quantitative traits. II. Genetic models for seed traits of crops.

Genetic models for quantitative seed traits with effects of several major genes and polygenes, as well as their GE interaction, were proposed. Mixed linear model approaches were suggested for analyzing the genetic models. Monte Carlo simulations were conducted to evaluate unbiasedness and efficiency for estimating fixed effects and variance components of the embryo and the endosperm models, including effects of a major gene from an unbalanced modified diallel mating design with nine parents, respectively. Simulation results showed that estimates of generalized least squares (GLS) were unbiased and efficient, while those of ordinary least squares (OLS) were almost as good as GLS. Minimum norm quadratic unbiased estimation (MINQUE) could obtain unbiased estimates of the variance components. It was also suggested that precision of MINQUE estimation would be improved with augmentation of experimental size. Data from a modified diallel design in upland cotton ( Gossypium hirsutum L.) were used as a worked example to illustrate the parameter estimation.

Journal Article↗
PubMed2003

Recent advances in human quantitative-trait-locus mapping: comparison of methods for selected sibling pairs.

During the past few years, there has been a great deal of new work on methods for mapping quantitative-trait loci by use of sibling pairs and sibships. There are several new methods based on linear regression, as well as several more that are based on score statistics. In theory, most of the new methods should be relatively robust to violations of distributional assumptions and to selected sampling, but, in practice, there has been little evaluation of how the methods perform on selected samples. We survey most of the new regression-based statistics and score statistics and propose a few minor variations on the score statistics. We use simulation to evaluate the type I error and the power of all of the statistics, considering (a) population samples of sibling pairs and (b) sibling pairs ascertained on the basis of at least one sibling with a trait value in the top 10% of the distribution. Most of the statistics have correct type I error for selected samples. The statistics proposed by Xu et al. and by Sham and Purcell are generally the most powerful, along with one of our score statistic variants. Even among the methods that are most powerful for "nice" data, some are more robust than others to non-Gaussian trait models and/or misspecified trait parameters.

Chromosome Mapping↗
PubMed2005

Optimising two-dye microarray designs for estimating associations with a quantitative trait.

We discuss how the samples should be arranged in two-dye microarray studies when the objective is to investigate associations between gene expression and quantitative traits measured on each sample. Because there is typically large between array variation, information about the association will come from the differences in traits and expression measurements between the two values hybridised to the two dyes on the same array. It is shown that within-slide correlation of trait values should be minimised. The arrangement of samples for which this occurs will depend on the trait values in question, and is a computationally demanding problem. An alternative is to minimise the rank correlation. We discuss this and related issues for different combinations of numbers of samples and arrays. Data analysis, including estimation of the variance components, is also described.

Algorithms↗
PubMed1999

Detection of quantitative trait loci affecting caffeine metabolism by interval mapping in a genome-wide scan of C3H/HeJ x APN F(2) mice.

Caffeine metabolite ratios have been widely used to measure cytochrome P-450 1A2 activity in humans. Serum paraxanthine/caffeine ratio is one such index of this activity. We had previously demonstrated genetic variation of this trait among inbred mouse strains. In the present study, we have undertaken a genome-wide scan for quantitative trait loci affecting this trait with an interval mapping approach on an F(2) intercross population of acetaminophen nonsusceptible and C3H/HeJ inbred mice. A statistically significant association (log-likelihood ratio = 25.0) between a locus on chromosome 9, which colocalized with the murine Cyp1a2 locus, and the plasma paraxanthine/caffeine ratio was identified. This result suggested the presence of an expression polymorphism affecting this gene. A second locus was identified on chromosome 1 (log-likelihood ratio = 9.7) for which no obvious candidate gene has been identified. The influence of this locus on the paraxanthine/caffeine index was more significant among males (log-likelihood ratio = 6.3) than females (log-likelihood ratio = 3.6). A third locus was identified on chromosome 4 with a less statistically robust association (log-likelihood ratio = 3.4) to the paraxanthine/caffeine phenotype. Collectively, these three loci accounted for 63.2% of the variation observed in the F(2) population for this phenotype. These results demonstrate the potential for genetic variation arising from factors other than CYP1A2 activity to influence the plasma paraxanthine/caffeine ratio in mice. This study demonstrates the utility of quantitative genetics in the analysis of polygenic drug metabolism.

Animals↗
PubMed2005

New joint covariance- and marginal-based tests for association and linkage for quantitative traits for random and non-random sampling.

We develop novel statistical tests for transmission disequilibrium testing (tests of linkage in the presence of association) for quantitative traits using parents and offspring. These joint tests utilize information in both the covariance (or more generally, dependency) between genotype and phenotype and the marginal distribution of genotype. Using computer simulation we test the validity (Type I error rate control) and power of the proposed methods, for additive, dominant, and recessive modes of inheritance, locus-specific heritability of the trait 0.05, 0.1, 0.2 with allele frequencies of P=0.2 and 0.4, and sample sizes of 500, 200, and 100 trios. Both random sampling and extreme sampling schemes were investigated. A multinomial logistic joint test provides the highest overall power irrespective of sample size, allele frequency, heritability, and modes of inheritance.

Algorithms↗
PubMed2006

Extreme rank selections for linkage analysis of quantitative trait loci using selected sib-pairs.

It is well known that linkage analysis using simple random sib-pairs has relatively low power for detecting quantitative trait loci with small genetic effects. The power can be substantially increased by using samples selected based on their trait values. Usually, samples that are obtained by truncation selection consist of random samples from a truncated trait distribution. In this article we propose an alternative method using extreme ranks for linkage analysis with selected sib-pairs. This approach approximates the truncation selection. With similar screening sizes and the same sample size of selected sib-pairs, the extreme rank selection and truncation method have similar power performance, both of which are substantially more powerful than when using random sib-pairs. Simulation results on the comparison of powers between the truncation selection and the extreme rank selection and/or random selection for linkage analysis are reported.

Genetic Linkage↗
PubMed2001

Population mixing and the adaptive divergence of quantitative traits in discrete populations: a theoretical framework for empirical tests.

Empirical tests for the importance of population mixing in constraining adaptive divergence have not been well grounded in theory for quantitative traits in spatially discrete populations. We develop quantitative-genetic models to examine the equilibrium difference between two populations that are experiencing different selective regimes and exchanging individuals. These models demonstrate that adaptive divergence is negatively correlated with the rate of population mixing (m, most strongly so when m is low), positively correlated with the difference in phenotypic optima between populations, and positively correlated with the amount of additive genetic variance (G, most strongly so when G is low). The approach to equilibrium is quite rapid (fewer than 50 generations for two populations to evolve 90% of the distance to equilibrium) when either heritability or mixing are not too low (h2 > 0.2 or m > 0.05). The theory can be used to aid empirical tests that: (1) compare observed divergence to that predicted using estimates of population mixing, additive genetic variance/covariance, and selection; (2) test for a negative correlation between population mixing and adaptive divergence across multiple independent population pairs; and (3) experimentally manipulate the rate of mixing. Application of the first two of these approaches to data from two well-studied natural systems suggests that population mixing has constrained adaptive divergence for color patterns in Lake Erie water snakes (Nerodia sipedon), but not for trophic traits in sympatric pairs of benthic and limnetic stickleback (Gasterosteus aculeatus). The theoretical framework we outline should provide an improved basis for future empirical tests of the role of population mixing in adaptive divergence.

Adaptation, Physiological↗
PubMed2003

Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice.

To investigate genetic contributions to individual variations of lipoprotein cholesterol concentrations, we performed quantitative trait locus/loci (QTL) analyses of an intercross of CAST/Ei and DBA/2J inbred mouse strains after feeding a high-cholesterol cholic acid diet for 10 weeks. In total, we identified four QTL for HDL cholesterol. Three of these were novel and were named Hdlq10 [20 centimorgans (cM), chromosome 4], Hdlq11 (48 cM, chromosome 6), and Hdlq12 (68 cM, chromosome 6). The fourth QTL, Hdl1 (48 cM, chromosome 2), confirmed a locus discovered previously using a breeding cross that employed different inbred mouse strains. In addition, we identified one novel QTL for total and non-HDL cholesterol (8 cM, chromosome 9) that we named Chol6. Hdlq10, colocalized with a mutagenesis-induced point mutation (Lch), also affecting HDL. We provide molecular evidence for Abca1 as the gene underlying Hdlq10 and Ldlr as the gene underlying Chol6 that, coupled with evidence generated by other researchers using knockout and transgenic models, causes us to postulate that polymorphisms of these genes, different from the mutations leading to Tangier's disease and familial hypercholesterolemia, respectively, are likely primary genetic determinants of quantitative variation of lipoprotein levels in mice and, by orthology, in the human population.

Animals↗