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At least 559 records · Page 31Linked to original sources
PubMed2002

The genetic architecture of Drosophila sensory bristle number.

We have mapped quantitative trait loci (QTL) for Drosophila mechanosensory bristle number in six recombinant isogenic line (RIL) mapping populations, each of which was derived from an isogenic chromosome extracted from a line selected for high or low, sternopleural or abdominal bristle number and an isogenic wild-type chromosome. All RILs were evaluated as male and female F(1) progeny of crosses to both the selected and the wild-type parental chromosomes at three developmental temperatures (18 degrees, 25 degrees, and 28 degrees ). QTL for bristle number were mapped separately for each chromosome, trait, and environment by linkage to roo transposable element marker loci, using composite interval mapping. A total of 53 QTL were detected, of which 33 affected sternopleural bristle number, 31 affected abdominal bristle number, and 11 affected both traits. The effects of most QTL were conditional on sex (27%), temperature (14%), or both sex and temperature (30%). Epistatic interactions between QTL were also common. While many QTL mapped to the same location as candidate bristle development loci, several QTL regions did not encompass obvious candidate genes. These features are germane to evolutionary models for the maintenance of genetic variation for quantitative traits, but complicate efforts to understand the molecular genetic basis of variation for complex traits.

Animals↗
PubMed2005

Genomics of the future: identification of quantitative trait loci in the mouse.

Positional cloning of quantitative trait loci in rodents is a common approach to identify genes involved in complex phenotypes, including genes important to human disease. However, cloning the causative genes has proved to be more difficult than determining their positions. New tools such as genomic sequence, clone libraries, and new genomic-based methods offer new approaches to identify these genes. Here we review how these new tools and approaches will improve our ability to discover the genes important in complex traits.

Animals↗
PubMed2006

Selection for sow longevity.

Sow longevity plays an important role in economically efficient piglet production because sow longevity is related to the number of piglets produced during its productive lifetime; however, selection for sow longevity is not commonly practiced in any pig breeding program. There is relatively little scientific literature concerning the genetic parameters (genetic variation and genetic correlations) or methods available for breeding value estimation for effective selection for sow longevity. This paper summarizes the current knowledge about the genetics of sow longevity and discusses the available breeding value estimation methods for sow longevity traits. The studies in the literature clearly indicate that sow longevity is a complex trait, and even the definition of sow longevity is variable depending on the researcher and research objective. In general, the measures and analyses of sow longevity can be divided into 1) continuous traits (e.g., productive lifetime) analyzed with proportional hazard models; and 2) more simple binary traits such as stayability until some predetermined fixed parity. Most studies have concluded that sufficient genetic variation exists for effective selection on sow longevity, and heritability estimates have ranged between 0.02 and 0.25. Moreover, sow longevity has shown to be genetically associated with prolificacy and leg conformation traits. Variable results from previous research have led to a lack of consensus among swine breeders concerning the valid methodology of estimating breeding values for longevity traits. One can not deny the superiority of survival analysis in the modeling approach of longevity data; however, multiple-trait analyses are not possible using currently available survival analysis software. Less sophisticated approaches have the advantage of evaluating multiple traits simultaneously, and thus, can use the genetic associations between sow longevity and other traits. Additional research is needed to identify the most efficient selection methods for sow longevity. Future research needs to concentrate on multiple trait analysis of sow longevity traits. Moreover, because longevity is a fitness trait, the nonadditive genetic effects (e.g., dominance) may play important role in the inheritance of sow longevity. Currently, not a single estimate for dominance variance of sow longevity could be identified from the scientific literature.

Animal Husbandry↗
PubMedDate not supplied

Gene mapping and marker clustering using Shannon's mutual information.

Finding the causal genetic regions underlying complex traits is one of the main aims in human genetics. In the context of complex diseases, which are believed to be controlled by multiple contributing loci of largely unknown effect and position, it is especially important to develop general yet sensitive methods for gene mapping. We discuss the use of Shannon's information theory for population-based gene mapping of discrete and quantitative traits and for marker clustering. Various measures of mutual information were employed in order to develop a comprehensive framework for gene mapping analyses. An algorithm aimed at finding so-called relevance chains of causal markers is proposed. Moreover, entropy measures are used in conjunction with multidimensional scaling to visualize clusters of genetic markers. The relevance chain algorithm successfully detected the two causal regions in a simulated scenario. The approach has also been applied to a published clinical study on autoimmune (Graves') disease. Results were consistent with those of standard statistical methods, but identified an additional locus of interest in the promotor region of the associated gene CTLA4. The developed software is freely available at http://www.Int.ei.tum.de/download/InfoGeneMap/.

Algorithms↗
PubMed1998

Expression of altered alpha2-adrenergic phenotypic traits in normotensive humans at genetic risk of hereditary (essential) hypertension.

BACKGROUND: Essential (hereditary) hypertension is a common, though complex, trait with substantial heritability, but a still-obscure mode of inheritance. In this disorder with relatively late onset, knowledge of phenotypes with earlier penetrance would aid genetic analyses, as well as assessment of risk. OBJECTIVE: Because alpha2-adrenergic receptor alterations are among the most heritable in experimental genetic hypertension, we hypothesized enhanced expression of alpha2-adrenergic phenotypic traits in still-normotensive humans at genetic risk of hypertension. METHODS: We evaluated hemodynamic (blood pressure, cardiac output, systemic vascular resistance, stroke volume, and cardiac contractility) and biochemical (plasma drug, catecholamine, renin, and chromogranin A levels) responses to alpha2-adrenergic blockade with intravenous yohimbine in 84 normotensive subjects stratified by genetic risk of essential hypertension (67 with positive family histories and 17 with negative family histories of hypertension), as well as 18 subjects with established essential hypertension. Results were evaluated by analysis of variance, normal likelihood ratio test, and by maximum likelihood analysis for bimodality (i.e. mixtures) of response distributions. RESULTS: Blood pressure rose (P<0.001) during alpha2-adrenergic blockade, with greater response (P<0.001) in members of the hypertensive than in members of the normotensive group. Hemodynamically, the rise in blood pressure resulted from an increase in cardiac output (P<0.001), with associated increases in stroke volume (P=0.002) and cardiac contractility (P=0.006), without an overall change in systemic vascular resistance. Biochemically, plasma norepinephrine (P<0.001), epinephrine (P=0.001), and chromogranin A (P=0.02) rose, suggesting augmentation of efferent exocytotic sympathoadrenal activity. Cardiac output and stroke volume responses were correlated to increments in plasma catecholamines (especially epinephrine) for the positive group, but not for the negative group. Baseline plasma catecholamines predicted increments of stroke volume after administration of yohimbine (P=0.003-0.007) for the positive but not for the negative group. Simultaneous comparison of means and variances of cardiac output and stroke volume alpha2-adrenergic responses, by using a normal likelihood ratio test, revealed highly significant (P=0.025 to P<0.0001) differences between the groups of subjects with and without family histories of hypertension. Frequency histogram suggested that there was a bimodal distribution of responses of stroke volume to alpha2-adrenergic blockade for the normotensive group with positive family histories of hypertension; maximum likelihood analysis strongly rejected the hypothesis of a unimodal distribution, whereas the hypothesis of bimodality could not be rejected (chi2=18.4, P=0.0004). The second (exaggerated) mode of response of stroke volume to alpha2-adrenergic blockade, defined by maximum likelihood analysis, was found for 9.5% of subjects in the normotensive group with positive family histories of hypertension, and was characterized by significantly different responses of cardiac output (P=0.001), stroke volume (P<0.001), contractility (P<0.001), heart rate (P=0.03), systemic vascular resistance (P<0.001), and epinephrine (P<0.001). Even prior to alpha2-adrenergic blockade, baseline stroke volume (P=0.01), heart rate (P=0.04), systemic vascular resistance (P=0.005), and catecholamine (P=0.001-0.005) values for this subgroup were different than control values. CONCLUSIONS: We conclude that heterogeneous, bimodally distributed hemodynamic responses to alpha2-adrenergic blockade in subjects with positive family histories of hypertension suggest a discrete subgroup with early expression of perhaps Mendelian traits associated with risk of later development of hypertension. Such phenotypic traits ('intermediate phenotypes'), with earlier penetrance than hypertension itself, can be

Adolescent↗
PubMed2005

Statistical tools for linkage analysis and genetic association studies.

Genetic mapping by linkage analysis has been an invaluable tool in the positional strategy to identify the molecular basis of many rare Mendelian disorders. With the attention of the scientific and medical community shifting towards the analysis of more common, complex traits, it has become necessary to develop new approaches that take into account the complexity of the genetic basis of these disorders and their possible interaction with other, nongenetic factors. Linkage disequilibrium studies are now becoming increasingly popular thanks to the advent of genotyping platforms that allow genome-wide searching for association between hundreds of thousands of random polymorphisms and disease phenotypes in large samples of unrelated individuals. Moreover, the definition of the disease phenotype itself is being reconsidered to include quantitative traits that may better define the underlying biologic mechanisms for many pathologic conditions. This article will review classic and new approaches to genetic mapping by linkage and association analysis and discuss the directions this field is likely to take in the near future.

Alleles↗
PubMed2007

Detection of novel quantitative trait loci for cutaneous melanoma by genome-wide scan in the MeLiM swine model.

Human cutaneous melanoma is a complex trait inherited in about 10% of cases. Although 2 high-risk genes, CDKN2A and CDK4, and 1 low risk gene, MC1R, have been identified, susceptibility genes remain to be discovered. Here, we attempted to determine new genomic regions linked to melanoma using the pig MeLiM strain, which develops hereditary cutaneous melanomas. We applied quantitative trait loci (QTL) mapping method to a significant genome-wide scan performed on 331 backcross pigs derived from this strain. QTLs were detected at chromosome-wide level for a melanoma synthetic trait corresponding to the development of melanoma. The peak positions on Sus scrofa chromosomes (SSC) were at 49.4 and 88.0 cM (SSC1), 56.0 cM (SSC13), 86.5 cM (SSC15) and 39.8 cM (SSC17), and, on SSC2, at 16.9 cM, in families derived from F1 males only (p < 0.05, except for SSC13, p < 0.01). Analysis of 7 precise specific traits revealed highly significant QTLs on SSC10 (ulceration), on SSC12 (presence of melanoma at birth), on SSC13 (lesion type), and on SSC16 and SSC17 (number of aggressive melanomas) at the respective positions 42.0, 95.6, 81.0, 45.3 and 44.8 cM (p < 0.001 and p < 0.05 respectively at the chromosome- and genome-wide levels). We also showed that MeLiM MC1R*2 allele, which determines black coat colour in pigs, predisposes significantly to melanoma. Interactions were observed between MC1R and markers located on SSC1 (p < 0.05). Taken together, these results indicate that MeLiM swine is a model for human multigenic diseases. Comparative mapping revealed human regions of interest to search for new melanoma susceptibility candidates.

Alleles↗
PubMed2006

Genetical genomics in livestock: potentials and pitfalls.

Genetical genomics combines gene mapping and gene expression approaches to identify loci controlling gene expression (eQTLs) that may underlie functional trait variation. The combination of genomic tools has great potential to facilitate dissection of complex traits, but studies need careful design and interpretation. Here we explore both the potential and the pitfalls of this approach with illustrations from actual studies. There are now an appreciable number of studies in model species and even humans demonstrating the feasibility of genetical genomics. However, most studies are too limited in size and design to unlock the full potential of the approach. Limited statistical power of studies exacerbates the problem of detection of false-positive eQTL and some reported results should be interpreted with caution. As one approach to more successful implementation of genetical genomics, we propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. These properties make it particularly suitable for livestock populations where many QTL are already in the public domain and potentially very large pedigreed populations can be accessed.

Animals↗
PubMedDate not supplied

Review of statistical methods for QTL mapping in experimental crosses.

Identification of quantitative trait loci (QTLs) in experimental animals is critical for understanding the biochemical bases of complex traits, and thus for the identification of drug targets. The author reviews the basic statistical methods for mapping QTLs in experimental crosses and comments on a number of the statistical issues to consider in the application of these methods.

Animals↗
PubMed1999

Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

Gene Frequency↗
PubMed2005

Genome-wide introgression lines and their use in genetic and molecular dissection of complex phenotypes in rice (Oryza sativa L.).

Tremendous efforts have been taken worldwide to develop genome-wide genetic stocks for rice functional genomic (FG) research since the rice genome was completely sequenced. To facilitate FG research of complex polygenic phenotypes in rice, we report the development of over 20,000 introgression lines (ILs) in three elite rice genetic backgrounds for a wide range of complex traits, including resistances/tolerances to many biotic and abiotic stresses, morpho-agronomic traits, physiological traits, etc., by selective introgression. ILs within each genetic background are phenotypically similar to their recurrent parent but each carries one or a few traits introgressed from a known donor. Together, these ILs contain a significant portion of loci affecting the selected complex phenotypes at which allelic diversity exists in the primary gene pool of rice. A forward genetics strategy was proposed and demonstrated with examples on how to use these ILs for large-scale FG research. Complementary to the genome-wide insertional mutants, these ILs opens a new way for highly efficient discovery, candidate gene identification and cloning of important QTLs for specific phenotypes based on convergent evidence from QTL position, expression profiling, functional and molecular diversity analyses of candidate genes, highlights the importance of genetic networks underlying complex phenotypes in rice that may ultimately lead to more complete understanding of the genetic and molecular bases of quantitative trait variation in rice.

Adaptation, Physiological↗
PubMed1996

Particulate versus integrated evolution of the upper body in late pleistocene humans: a test of two models.

Evolutionary biologists are largely polarized in their approaches to integrating microevolutionary and macroevolutionary processes. Neo-Darwinians typically seek to identify population-level selective and genetic processes that culminate in macroevolutionary events. Epigeneticists and structuralists, on the other hand, emphasize developmental constraints on the action of natural selection, and highlight the role of epigenetic shifts in producing evolutionary change in morphology. Accordingly, the ways in which these paradigms view and address morphological contrasts between classes of related organisms differ. These paradigms, although seldomly explicitly stated, emerge in paleoanthropology as well. Considerations of postcranial morphological contrasts between archaic and modern humans typically fall into one of two broad interpretive models. The first derives from the neo-Darwinian perspective and holds that evolution in the postcranial skeleton was largely mosaic (operating in a particulate manner), and that temporal change in specific traits informs us about behavioral shifts or genetic evolution affecting isolated anatomical regions (i.e., adaptive behavioral inferences can be made from comparative studies of individual trait complexes). The alternative model follows from the epigeneticist paradigm and sees change in specific postcranial traits as correlated responses to change in overall body form (involving shifts in regulation of skeletal growth, or selective and developmental responses to broad adaptive shifts). By this view, integration of functional systems both constrains and directs evolution of various traits, and morphological contrasts inform us about overall change in body form related to change in such things as overall growth patterns, climatic adaptation, and technological dependency. These models were tested by confirmatory factor analysis using measures of upper body form and upper limb morphological traits in Eurasian Neandertal and early modern fossils and recent human samples. Results indicate (1) a model of morphological integration fits the data better than a model of no integration, but (2) this integration accounts for less than half of the variance in upper limb traits, suggesting a high degree of tolerance for particulate evolution in the context of an integrated upper body plan. Significant relationships were detected between joint shapes and body size, between humeral shaft shape and body size and chest shape, and between measures of biomechanical efficiency and robusticity. The observed morphological differences between late archaic and early modern humans reflect particulate evolution in the context of constraints imposed by genetic and morphological integration. While particulate approaches to interpreting the fossil record appear to be justified, attention must also be paid to delineating the nature and extent of morphological integration and its role in both constraining and producing observed patterns of variation between groups. Confirmatory factor analysis provides a means of examining trait covariance matrices, and serves as a useful method of identifying patterns of integration in morphology.

Biological Evolution↗
PubMed2025

Cosmopolitan inversions have a major impact on trait variation and the power of different GWAS approaches to identify associations.

The ability of genomic inversions to reduce recombination and generate linkage can have a major impact on genetically based phenotypic variation in populations. However, the increase in linkage associated with inversions can create hurdles for identifying associations between loci within inversions and the traits they impact. As a consequence, the role of inversions in mediating genetic variation in complex traits remains to be fully understood. This study uses the fruit fly Drosophila melanogaster to investigate the impact of inversions on trait variation. We tested the effects of common inversions among a diverse assemblage of traits including aspects of behavior, morphology, and physiology, and identified that the cosmopolitan inversions In(2L)t and In(3R)Mo are associated with many traits. We compared the ability of different approaches of accounting for relatedness and inversion presence during genome-wide association to identify signals of association with SNPs. We report that commonly used association methods are underpowered within inverted regions, while alternative approaches such as leave-one-chromosome-out improve the ability to identify associations. In all, our research enhances our understanding of inversions as components of trait variation and provides insight into approaches for identifying genomic regions driving these associations.

Drosophila melanogaster↗
PubMed2006

Genetic basis of phenotypic correlations among growth traits in hybrid willow (Salix dasycladosxS. viminalis) grown under two water regimes.

Phenotypic correlations and quantitative trait loci (QTL) for important growth traits and a surrogate of intrinsic water-use efficiency (leaf delta(13)C) were analysed in a willow pedigree of 92 full-sibling clones grown under two water regimes. The major objective was to examine the genetic basis of the phenotypic correlations. Cuttings of Salix were glasshouse-grown during one growing season. The relative growth rate (RGR) and underlying traits were assessed. QTL analysis was conducted based on an available linkage map for Salix. Leaf area productivity and leaf nitrogen productivity were more important in determining RGR than leaf area ratio and specific leaf area. However, phenotypic correlations among growth traits partly varied between the two environments. QTL were detected for most growth traits, among them many common QTL for different traits. The QTL pattern reflected the phenotypic correlation pattern. None of the QTL for the complex traits was consistent across the different environments. The results demonstrate a genetic basis for phenotypic correlations among growth traits in Salix, and provide evidence for the existence of 'master switches' regulating some of the traits.

Biomass↗
PubMed2005

Common variants in myocardial ion channel genes modify the QT interval in the general population: results from the KORA study.

Altered myocardial repolarization is one of the important substrates of ventricular tachycardia and fibrillation. The influence of rare gene variants on repolarization is evident in familial long QT syndrome. To investigate the influence of common gene variants on the QT interval we performed a linkage disequilibrium based SNP association study of four candidate genes. Using a two-step design we analyzed 174 SNPs from the KCNQ1, KCNH2, KCNE1, and KCNE2 genes in 689 individuals from the population-based KORA study and 14 SNPs with results suggestive of association in a confirmatory sample of 3277 individuals from the same survey. We detected association to a gene variant in intron 1 of the KCNQ1 gene (rs757092, +1.7 ms/allele, P=0.0002) and observed weaker association to a variant upstream of the KCNE1 gene (rs727957, +1.2 ms/allele, P=0.0051). In addition we detected association to two SNPs in the KCNH2 gene, the previously described K897T variant (rs1805123, -1.9 ms/allele, P=0.0006) and a gene variant that tags a different haplotype in the same block (rs3815459, +1.7 ms/allele, P=0.0004). The analysis of additive effects by an allelic score explained a 10.5 ms difference in corrected QT interval length between extreme score groups and 0.951 of trait variance (P<0.00005). These results confirm previous heritability studies indicating that repolarization is a complex trait with a significant heritable component and demonstrate that high-resolution SNP-mapping in large population samples can detect and fine map quantitative trait loci even if locus specific heritabilities are small.

Adult↗
PubMed2006

Fine mapping reveals sex bias in quantitative trait loci affecting growth, skeletal size and obesity-related traits on mouse chromosomes 2 and 11.

Previous speed congenic analysis has suggested that the expression of growth and obesity quantitative trait loci (QTL) on distal mouse chromosomes (MMU) 2 and 11, segregating between the CAST/EiJ (CAST) and C57BL/6J-hg/hg (HG) strains, is dependent on sex. To confirm, fine map, and further evaluate QTL x sex interactions, we constructed congenic by recipient F2 crosses for the HG.CAST-(D2Mit329-D2Mit457)N(6) (HG2D) and HG.CAST-(D11Mit260-D11Mit255)N(6) (HG11) congenic strains. Over 700 F2 mice were densely genotyped and phenotyped for a panel of 40 body and organ weight, skeletal length, and obesity-related traits at 9 weeks of age. Linkage analysis revealed 20 QTL affecting a representative subset of phenotypes in HG2DF2 and HG11F2 mice. The effect of sex was quantified by comparing two linear models: the first model included sex as an additive covariate and the second incorporated sex as an additive and an interactive covariate. Of the 20 QTL, 8 were sex biased, sex specific, or sex antagonistic. Most traits were regulated by single QTL; however, two closely linked loci were identified for five traits in HG2DF2 mice. Additionally, the confidence intervals for most QTL were significantly reduced relative to the original mapping results, setting the stage for quantitative trait gene (QTG) discovery. These results highlight the importance of assessing the contribution of sex in complex trait analyses.

Animals↗
PubMed2002

Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping.

A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.

Animals↗
PubMed2001

The biological basis of epistasis between quantitative trait loci for flavone and 3-deoxyanthocyanin synthesis in maize (Zea mays L.).

A major weakness in our understanding of the genetic basis of complex traits has been that of defining the extent and biological basis of epistasis. Our research group has been studying the genetic control of the accumulation of maysin, a C-glycosyl flavone, in maize, Zea mays (L.), silks. Previously, we demonstrated the importance of the p1 locus as a QTL for maysin synthesis. The p1 locus often exhibits significant epistatic interactions with other loci. We developed a mapping population, (W23al x GT119)F2, specifically designed to test whether genes in an intersecting pathway might be detected as QTLs for maysin synthesis and result in epistatic interaction effects. The a1 gene is not required for the synthesis of flavones but is required for the synthesis of 3-deoxyanthocyanins, an intersecting pathway, in maize silks. The p1 locus (P < 0.0001) was a QTL for both flavones and 3-deoxyanthocyanins. The a1 locus was also highly significant (P < 0.0001) for both traits, as was the p1 x a1 epistatic interaction (P < 0.0001). Our results demonstrate that altering the flux of biochemical intermediates between pathways may be the biological basis of major QTL effects and epistatic interactions.

Alleles↗