Journal articles: 'Expression QTL'

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Peirce, Jeremy L., Hongqiang Li, Jintao Wang, Kenneth F. Manly, Robert J. Hitzemann, John K. Belknap, Glenn D. Rosen, et al. "How replicable are mRNA expression QTL?" Mammalian Genome 17, no. 6 (June 2006): 643–56. http://dx.doi.org/10.1007/s00335-005-0187-8.

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Penning, Bryan W., Gurmukh S. Johal, and Michael D. McMullen. "A major suppressor of cell death, slm1, modifies the expression of the maize (Zea mays L.) lesion mimic mutation les23." Genome 47, no. 5 (October 1, 2004): 961–69. http://dx.doi.org/10.1139/g04-046.

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Disease lesion mimics provide an excellent biological system to study the genetic basis of cell death in plants. Many lesion mimics show variation in phenotype expression in different genetic backgrounds. Our goal was to identify quantitative trait loci (QTL) modifying lesion mimic expression thereby identifying genetic modifiers of cell death. A recessive lesion mimic, les23, in a severe-expressing line was crossed to the maize inbred line Mo20W, a lesion-suppressing line, and an F2 population was developed for QTL analysis. In addition to locating les23 to the short arm of chromosome 2, this analysis detected significant loci for modification of lesion expression. One highly significant locus was found on the long arm of chromosome 2. The Mo20W allele at this QTL significantly delayed initiation of the lesion phenotype and decreased the final lesion severity. Other QTL with lesser effect affected severity of lesion expression without affecting lesion initiation date. Our results demonstrate that dramatic change in lesion phenotype can be controlled by a single major QTL. The presumed function of this QTL in normal plants is to regulate some aspect of the cell death pathway underlying the les23 phenotype.Key words: genetic background, quantitative trait locus, phenotype suppression, Mo20W, corn.

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Han, Bing, Naomi S. Altman, Jessica A. Mong, Laura Cousino Klein, Donald W. Pfaff, and David J. Vandenbergh. "Comparing Quantitative Trait Loci and Gene Expression Data." Advances in Bioinformatics 2008 (September 16, 2008): 1–6. http://dx.doi.org/10.1155/2008/719818.

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We develop methods to compare the positions of quantitative trait loci (QTL) with a set of genes selected by other methods, such as microarray experiments, from a sequenced genome. We apply our methods to QTL for addictive behavior in mouse, and a set of genes upregulated in a region of the brain associated with addictive behavior, the nucleus accumbens (NA). The association between the QTL and NA genes is not significantly stronger than expected by chance. However, chromosomes 2 and 16 do show strong associations suggesting that genes on these chromosomes might be associated with addictive behavior. The statistical methodology developed for this study can be applied to similar studies to assess the mutual information in microarray and QTL analyses.

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Viñuela, Ana, L. Basten Snoek, Joost A. G. Riksen, and Jan E. Kammenga. "Aging Uncouples Heritability and Expression-QTL inCaenorhabditis elegans." G3: Genes|Genomes|Genetics 2, no. 5 (May 2012): 597–605. http://dx.doi.org/10.1534/g3.112.002212.

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Zou, Wei, and Zhao-Bang Zeng. "Multiple interval mapping for gene expression QTL analysis." Genetica 137, no. 2 (May 9, 2009): 125–34. http://dx.doi.org/10.1007/s10709-009-9365-z.

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Wu, Wei-Ren, Wei-Ming Li, Ding-Zhong Tang, Hao-Ran Lu, and A. J. Worland. "Time-Related Mapping of Quantitative Trait Loci Underlying Tiller Number in Rice." Genetics 151, no. 1 (January 1, 1999): 297–303. http://dx.doi.org/10.1093/genetics/151.1.297.

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Abstract Using time-related phenotypic data, methods of composite interval mapping and multiple-trait composite interval mapping based on least squares were applied to map quantitative trait loci (QTL) underlying the development of tiller number in rice. A recombinant inbred population and a corresponding saturated molecular marker linkage map were constructed for the study. Tiller number was recorded every 4 or 5 days for a total of seven times starting at 20 days after sowing. Five QTL were detected on chromosomes 1, 3, and 5. These QTL explained more than half of the genetic variance at the final observation. All the QTL displayed an S-shaped expression curve. Three QTL reached their highest expression rates during active tillering stage, while the other two QTL achieved this either before or after the active tillering stage.

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McIntyre, C. Lynne, David Seung, Rosanne E. Casu, Gregory J. Rebetzke, Ray Shorter, and Gang Ping Xue. "Genotypic variation in the accumulation of water soluble carbohydrates in wheat." Functional Plant Biology 39, no. 7 (2012): 560. http://dx.doi.org/10.1071/fp12077.

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Water-soluble carbohydrates (WSC) stored in the stems and leaf sheaths of winter cereals provide an important source of assimilate for remobilisation during grain-filling. Consequently, WSC are a major contributor to wheat grain yield and grain size in all environments but especially where photosynthesis is compromised as occurs where water is limiting. Breeding programs targeting greater WSC should provide improved varieties with greater and more stable yields in stress environments. To facilitate selection for WSC, genetic and genomic approaches are being used to determine the genetic basis of – and define DNA probes for – marker-aided selection for this important drought-adaptive trait. Empirical studies have identified both WSC concentration and content to be under complex genetic control of many genes. Quantitative trait loci (QTL) for WSC have been identified in several wheat populations with individual QTL explaining small amounts of phenotypic variation, typically of less than 20%. Many of these QTL are common across multiple, genetically-unrelated wheat populations. Evaluation of gene expression in high and low WSC wheat progeny lines from a well characterised wheat population has identified significant differences in expression of genes from different gene categories. For example, high WSC progeny lines have higher levels of expression of genes involved in carbohydrate metabolism and lower levels of expression of genes involved in cell wall and amino acid metabolism than low WSC lines. Genetic mapping reveals several candidate genes co-locating with QTL for WSC. In addition, expression QTL (eQTL) for selected candidate genes co-locate with WSC QTL; co-location of the genes and eQTL with WSC QTL make these genes stronger candidate genes for the WSC trait.

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Ronald, James, and Joshua M. Akey. "The Evolution of Gene Expression QTL in Saccharomyces cerevisiae." PLoS ONE 2, no. 8 (August 1, 2007): e678. http://dx.doi.org/10.1371/journal.pone.0000678.

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Hitzemann, Robert J. "ON THE INTEGRATION OF GENE EXPRESSION AND QTL ANALYSES." Alcoholism: Clinical & Experimental Research 28, Supplement (August 2004): 54A. http://dx.doi.org/10.1097/00000374-200408002-00284.

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de Koning, Dirk-Jan, Henk Bovenhuis, and Johan A. M. van Arendonk. "On the Detection of Imprinted Quantitative Trait Loci in Experimental Crosses of Outbred Species." Genetics 161, no. 2 (June 1, 2002): 931–38. http://dx.doi.org/10.1093/genetics/161.2.931.

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Abstract In this article, the quantitative genetic aspects of imprinted genes and statistical properties of methods to detect imprinted QTL are studied. Different models to detect imprinted QTL and to distinguish between imprinted and Mendelian QTL were compared in a simulation study. Mendelian and imprinted QTL were simulated in an F2 design and analyzed under Mendelian and imprinting models. Mode of expression was evaluated against the H0 of a Mendelian QTL as well as the H0 of an imprinted QTL. It was shown that imprinted QTL might remain undetected when analyzing the genome with Mendelian models only. Compared to testing against a Mendelian QTL, using the H0 of an imprinted QTL gave a higher proportion of correctly identified imprinted QTL, but also gave a higher proportion of false inference of imprinting for Mendelian QTL. When QTL were segregating in the founder lines, spurious detection of imprinting became more prominent under both tests, especially for designs with a small number of F1 sires.

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Nebor, Danitza, Raymond F. Robledo, Aleena Arakaki, Lionel Blanc, and Luanne L. Peters. "Mechanisms Regulating Increased Embryonic βh1 Globin Expression in Adult Nan anemic Mice." Blood 124, no. 21 (December 6, 2014): 742. http://dx.doi.org/10.1182/blood.v124.21.742.742.

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Abstract Sickle Cell Disease affects 90-100,000 in the US including 1/500 African-Americans born each year. Elevation of fetal hemoglobin (HbF) by co-inheritance of positive genetic modifiers of HbF expression or hydroxyurea (HU) treatment ameliorates disease severity. Because HU can have significant side effects, novel therapies aimed at elevating postnatal HbF expression are actively being sought. Three major loci modify HbF expression. Together, they account for ~50% of the variation in HbF expression, indicating that additional modifiers exist. Previously, we described the semi-dominant inbred mouse model Nan (neonatal anemia) that carries a missense mutation (E339D) in the second zinc finger of Krüppel-like factor 1 (KLF1/formerly EKLF) causing severe anemia accompanied by a striking failure of hemoglobin switching in Nan/+ mice (homozygotes die in utero). Embryonic βh1 globin expression is upregulated in Nan E14.5 fetal liver and in adult spleen where, remarkably, it accounts for nearly 100% of β-like globin gene expression. To extend these studies, we examined potential mechanisms regulating βh1 expression in adult Nan. Nan expression of Bcl11a, a downstream target of KLF1 that plays a major, conserved role in β-like globin gene switching, is 60-80% that of both untreated and phenylhydrazine treated (PHZ) wild type (WT) controls in the spleen. In peripheral blood, Nan BCL11A protein level is >50% of WT by western blotting. Importantly, prior studies by other investigators showed that newborn Bcl11a heterozygous knockout mice expressing Bcl11a at 50% of WT levels are haplosufficient, showing no differences in β-like globin gene expression. These data indicate that upregulated βh1 expression in Nan is BCL11A independent. We next examined erythropoiesis by flow cytometry using CD44, Ter119, and forward scatter (FSC) as markers. Nucleated erythroid precursors were strikingly decreased in Nan vs. PHZ-treated and phlebotomized (PHB) spleen, unusual in an anemic mouse model. Similar results were obtained using CD71, Ter119 and FSC gating. Despite this, βh1 expression normalized to saline-injected non-anemic controls was dramatically higher in Nan (93.0 ± 13.7, AU, X ± SEM) than either PHZ (3.6 ± 0.7) or PHB (7.4 ± 0.7) mice (p < 0.0001). Thus, increased βh1 in Nan is not simply due to stress erythropoiesis with concomitantly increased erythroid precursors. To analyze βh1 expression genetically, we constructed two Nan congenic lines on two different inbred genetic backgrounds, BALB/cBy and 129/SvImJ. Marked variation in adult spleen βh1 expression levels is seen among the three Nan strains. Similarly, we analyzed βh1 expression in an outbred high resolution mapping population derived from eight inbred strains, the diversity outcross (DO). Substantial variation in expression was seen among DO individuals. These data firmly establish the existence of modifying genes exerting profound influences on βh1 expression. We established an F2 intercross between 129S1/SvImJ-Nan/+ and C57BL/6J mice to take advantage of both Nan and DO mice to identify quantitative trait loci (QTL) modifying βh1 expression. Preliminary statistical analysis of 173 phenotyped (βh1 expression by RT-PCR) and SNP-genotyped F2 Nan/+ mice using R/qtl software identified a highly significant QTL for βh1 on Chr 7 encompassing the β-globin cluster and 3 suggestive QTL (Chr 4, 5 and 14). Analysis of 261 DO mice using QTL/ReL software identified 2 significant QTL (Chr 6, 7) and 6 suggestive QTL (Chr 2, 4[2], 6, 10, 14), with three in common with the QTL identified in F2 mice. Our analyses to date identify QTL overlapping three loci known to influence β-like globin gene switching (the β globin locus, Chr 7; LSD1, Chr 4; Mi-2β, Chr 6), providing proof of principle for our strategy. More importantly, additional loci identified contain no known modifiers, indicating the influence of novel genes. In summary, elevated βh1 expression in adult Nan spleen (1) occurs independently of Bcl11a; (2) is not mediated solely by stress erythropoiesis; (3) is highly influenced by genetic background; and (4) is influenced by novel genetic regulators of β-like globin switching. Disclosures No relevant conflicts of interest to declare.

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Cracchiolo, Danny, Jason W. Swick, Lucy McKiernan, Erica Sloan, Supriya Raina, Charles Sloan, and Douglas L. Wendell. "Estrogen-Dependent Growth of a Rat Pituitary Tumor Involves, But Does Not Require, a High Level of Vascular Endothelial Growth Factor." Experimental Biology and Medicine 227, no. 7 (July 2002): 492–99. http://dx.doi.org/10.1177/153537020222700714.

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Long-term (10-week) treatment of Fischer 344 (F344) rats with the synthetic estrogen diethylstilbestrol (DES) increases the level of vascular endothelial growth factor (VEGF) in the pituitary. This is concurrent with the development of a large tumor of the pituitary of F344 rats. A role for VEGF in estrogendependent pituitary tumor growth is also supported by the fact that pituitary VEGF level is not increased by estrogen treatment in rats of the tumor-resistant Brown Norway (BN) strain. However, VEGF is not increased by estrogen treatment in an F1 hybrid of F344 and BN, even though F1 hybrid rats do form pituitary tumors in response to estrogen. Quantitative trait locus (QLT) mapping reveals that control of estrogen-dependent VEGF expression is linked to the Edpm5 QTL, which was previously identified as a QTL for estrogen-dependent pituitary tumor growth. In contrast, the QTL Edpm2-1 and Edpm9-2, which have been shown to each have a significant effect on estrogendependent pituitary mass of a magnitude similar to Edpm5, do not have any effect on VEGF level. Taken together, our results support the association of VEGF expression with growth of the estrogen-Induced rat pituitary tumor, as has been reported by others, but they also indicate that there is significant pathways of growth regulation that are independent of high-level VEGF expression.

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Lu, Hong, Huai Jin Guan, Hui Chen, and Lu Lu. "Genetic Regulatory Network Analysis for Rpe65 in the Eye of BXD Mice." Advanced Materials Research 282-283 (July 2011): 248–52. http://dx.doi.org/10.4028/www.scientific.net/amr.282-283.248.

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Previous studies have revealed that the mutation of Rpe65plays a critical role in inherited retinal dystrophies. However, little is known about the genetic regulatory network for Rpe65 and inherited retinal dystrophies. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Rpe65 expression in the eye of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Rpe65exhibited much variation in the eye across the BXD RI strains and between the parental strains, C57BL/6J and DBA/2J. Expression QTL (eQTL) mapping showed that one microarray probe set of Rpe65 has highly significant linkage (Likelihood Ratio Statistic) scores. Moreover, the QTL was mapped to within 3 Mb of the location of the gene itself (Rpe65) as a cis-acting QTL. Through mapping the joint modulation of Rpe65, we identified Ches1/Foxn3 as downstream gene of Rpe65. Then the gene co-regulatory network analysis was constructed. The genetic genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to inherited retinal dystrophies.

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Yan, Juqiang, Jun Zhu, Cixin He, Mebrouk Benmoussa, and Ping Wu. "Molecular Dissection of Developmental Behavior of Plant Height in Rice (Oryza sativa L.)." Genetics 150, no. 3 (November 1, 1998): 1257–65. http://dx.doi.org/10.1093/genetics/150.3.1257.

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Abstract A doubled haploid population of 123 lines from IR64/Azucena was used to dissect the developmental behavior and genotype by environment interaction for plant height by conditional and unconditional quantitative trait loci (QTL) mapping methods in rice. It was shown that the number of QTL detected was different at various measuring stages. Some QTL could be detected at all stages and some only at one or several stages. More QTL could be found on the basis of time-dependent measures of different stages. By conditional QTL mapping of time-dependent measures, it is possible to reveal dynamic gene expression for quantitative traits. Mapping QTL for genetic main effects and GE interaction effects could help us in understanding the nature of QTL × environment interaction for the development of quantitative traits.

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Stylianou, Ioannis M., Michael Clinton, Peter D. Keightley, Clare Pritchard, Zuzzana Tymowska-Lalanne, Lutz Bünger, and Simon Horvat. "Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways." Physiological Genomics 20, no. 3 (February 10, 2005): 224–32. http://dx.doi.org/10.1152/physiolgenomics.00183.2004.

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Obesity-related diseases are poised to become the primary cause of death in developed nations. While a number of monogenic causes of obesity have recently been identified, these are responsible for only a small proportion of human cases of obesity. Quantitative trait locus (QTL) studies using animal models have revealed hundreds of potential loci that affect obesity; however, few have been further analyzed beyond the original QTL scan. We previously mapped four QTL in an F2 between divergently selected Fat (F) and Lean (L) lines. A QTL of large effect on chromosome 15 ( Fob3) was subsequently mapped to a higher resolution into two smaller-effect QTL ( Fob3a and Fob3b) using crosses between the F-line and a congenic line containing L-line alleles at the Fob3 QTL region. Here we report the gene expression characterization of Fob3b. Microarray expression analysis using the NIA-NIH 15K cDNA array set containing 14,938 mouse ESTs was employed to identify candidate genes and pathways that are differentially expressed between the F-line and a congenic line containing only the Fob3b QTL ( Fob3b-line). Our study suggests squalene epoxidase (Sqle), a cholesterol biosynthesis enzyme, as a strong positional candidate gene for Fob3b. Several other cholesterol biosynthesis pathway genes unlinked to Fob3b were found to be differentially expressed, suggesting that a perturbation of this pathway could be in part responsible for the phenotypic difference between the F-line and Fob3b-line mice.

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Prothro, Jason, Hussein Abdel-Haleem, Eleni Bachlava, Victoria White, Steven Knapp, and Cecilia McGregor. "Quantitative Trait Loci Associated with Sex Expression in an Inter-subspecific Watermelon Population." Journal of the American Society for Horticultural Science 138, no. 2 (March 2013): 125–30. http://dx.doi.org/10.21273/jashs.138.2.125.

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Sex expression is an important trait in watermelon (Citrullus lanatus), in which monoecious, andromonoecious, and trimonoecious forms are present. The andromonoecious trait is highly undesirable in watermelon breeding programs because it would require emasculation during hybrid development. In contrast to other cucurbits such as melon (Cucumis melo) and cucumber (Cucumis sativus) in which the genes involved in sex expression are well described and have been cloned, only the inheritance of the a gene associated with the andromonoecious trait has been described in watermelon. We used an intersubspecific C. lanatus var. lanatus × C. lanatus var. citroides F2 population to map quantitative trait loci (QTL) associated with percent male (%M), percent female (%F), percent hermaphrodite (%HM), and percent female of pistillate [%F/P (female + hermaphrodite)] flowers. Four chromosomal regions were identified that were associated with sex expression in watermelon. Major QTL for %F, %HM, and %F/P were colocalized on linkage group 11A and explained 31.3% to 37.7% of the phenotypic variation observed for the three traits. These QTL are suggested to be the location of the a gene in watermelon. Markers linked to two of the four QTL identified were located within 1 Mb of a 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene on the watermelon draft genome. ACS genes play a key role in sex expression in melon and cucumber and these genes are therefore candidate genes for further studies to elucidate this trait in another economically important cucurbit crop. The QTL and candidate genes identified in the present study lay the foundation for marker-assisted selection for sex expression traits in watermelon.

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Velez-Irizary, Deborah, Sebastian Casiro, Kaitlyn R. Daza, Ronald O. Bates, Nancy E. Raney, Juan P. Steibel, and Catherine Ernst. "33 Young Scholar Presentation: Expression quantitative trait loci and allele-specific expression exhibiting joint association with polygenic trait phenotypes in pigs." Journal of Animal Science 97, Supplement_2 (July 2019): 19. http://dx.doi.org/10.1093/jas/skz122.035.

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Abstract Advancements in sequencing technology, improvements in genome annotation, and development of quantitative genetic models have been instrumental to the significant genetic gains achieved in pork production. Several quantitative trait loci (QTL) have been identified for growth, meat quality and carcass composition (GMC) phenotypes, however, the biological mechanisms underlying most QTL remain unknown. Functional genomic analysis can reveal insights on the genetic architecture of complex traits, and transcriptomic profiling of skeletal muscle during the conversion of muscle to meat can identify critical regulators of GMC phenotypes. Gene transcripts obtained with RNA-seq of longissimus muscle from 168 pigs were used to estimate gene expression variation subject to genetic control by mapping expression QTL (eQTL) and allele-specific expression (ASE). A total of 334 eQTL were mapped (FDR≤0.01) and joint association of eQTL with phenotypic QTL (pQTL) segregating in our population revealed 16 genes significantly associated with 21 pQTL for GMC phenotypes. ASE analysis facilitates the identification of cis-acting regulation of transcript abundance. We tested for ASE in 69,502 coding SNP (cSNP) and a total of 18,234 cSNP with significant ASE were identified (FDR≤0.01). A gene-wise conditional analysis fitting all ASE cSNP per gene for each phenotype identified 60 genes associated with GMC phenotypes. A comparison of eQTL with ASE cSNP showed an overlap of 136 genes. Pearson correlations of peak eQTL SNP with ASE cSNP was significant for 51% of these genes. The ASE analysis showed more precision in the identification of cis-acting effects than the genome-wide eQTL analysis; however, both approaches provide valuable information on the regulation of transcript abundance. For instance, we observed 24 genes associated with distant eQTL (trans effects) and exhibiting ASE. This study provides new information on the complex regulation of the pig longissimus muscle transcriptome and associations with measurable differences in economically important phenotypic traits.

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Brown, Garth R., Daniel L. Bassoni, Geoffrey P. Gill, Joseph R. Fontana, Nicholas C. Wheeler, Robert A. Megraw, Mark F. Davis, Mitchell M. Sewell, Gerald A. Tuskan, and David B. Neale. "Identification of Quantitative Trait Loci Influencing Wood Property Traits in Loblolly Pine (Pinus taedaL.). III. QTL Verification and Candidate Gene Mapping." Genetics 164, no. 4 (August 1, 2003): 1537–46. http://dx.doi.org/10.1093/genetics/164.4.1537.

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AbstractA long-term series of experiments to map QTL influencing wood property traits in loblolly pine has been completed. These experiments were designed to identify and subsequently verify QTL in multiple genetic backgrounds, environments, and growing seasons. Verification of QTL is necessary to substantiate a biological basis for observed marker-trait associations, to provide precise estimates of the magnitude of QTL effects, and to predict QTL expression at a given age or in a particular environment. Verification was based on the repeated detection of QTL among populations, as well as among multiple growing seasons for each population. Temporal stability of QTL was moderate, with approximately half being detected in multiple seasons. Fewer QTL were common to different populations, but the results are nonetheless encouraging for restricted applications of marker-assisted selection. QTL from larger populations accounted for less phenotypic variation than QTL detected in smaller populations, emphasizing the need for experiments employing much larger families. Additionally, 18 candidate genes related to lignin biosynthesis and cell wall structure were mapped genetically. Several candidate genes colocated with wood property QTL; however, these relationships must be verified in future experiments.

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Bao, Lei, Xuefeng Xia, and Yan Cui. "Expression QTL Modules as Functional Components Underlying Higher-Order Phenotypes." PLoS ONE 5, no. 12 (December 13, 2010): e14313. http://dx.doi.org/10.1371/journal.pone.0014313.

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Guo, L. B., Y. Z. Xing, H. W. Mei, C. G. Xu, C. H. Shi, P. Wu, and L. J. Luo. "Dissection of component QTL expression in yield formation in rice." Plant Breeding 124, no. 2 (April 2005): 127–32. http://dx.doi.org/10.1111/j.1439-0523.2005.01093.x.

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Huang, Tao, and Yu-Dong Cai. "An Information-Theoretic Machine Learning Approach to Expression QTL Analysis." PLoS ONE 8, no. 6 (June 25, 2013): e67899. http://dx.doi.org/10.1371/journal.pone.0067899.

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Miller, Anna K., Anlu Chen, Jacquelaine Bartlett, Li Wang, Scott M. Williams, and David A. Buchner. "A Novel Mapping Strategy Utilizing Mouse Chromosome Substitution Strains Identifies Multiple Epistatic Interactions That Regulate Complex Traits." G3: Genes|Genomes|Genetics 10, no. 12 (October 6, 2020): 4553–63. http://dx.doi.org/10.1534/g3.120.401824.

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The genetic contribution of additive vs. non-additive (epistatic) effects in the regulation of complex traits is unclear. While genome-wide association studies typically ignore gene-gene interactions, in part because of the lack of statistical power for detecting them, mouse chromosome substitution strains (CSSs) represent an alternate approach for detecting epistasis given their limited allelic variation. Therefore, we utilized CSSs to identify and map both additive and epistatic loci that regulate a range of hematologic- and metabolism-related traits, as well as hepatic gene expression. Quantitative trait loci (QTL) were identified using a CSS-based backcross strategy involving the segregation of variants on the A/J-derived substituted chromosomes 4 and 6 on an otherwise C57BL/6J genetic background. In the liver transcriptomes of offspring from this cross, we identified and mapped additive QTL regulating the hepatic expression of 768 genes, and epistatic QTL pairs for 519 genes. Similarly, we identified additive QTL for fat pad weight, platelets, and the percentage of granulocytes in blood, as well as epistatic QTL pairs controlling the percentage of lymphocytes in blood and red cell distribution width. The variance attributed to the epistatic QTL pairs was approximately equal to that of the additive QTL; however, the SNPs in the epistatic QTL pairs that accounted for the largest variances were undetected in our single locus association analyses. These findings highlight the need to account for epistasis in association studies, and more broadly demonstrate the importance of identifying genetic interactions to understand the complete genetic architecture of complex traits.

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Kebede, Hirut, Paxton Payton, Hanh Thi My Pham, Randy D. Allen, and Robert J. Wright. "Toward Coalescing Gene Expression and Function with QTLs of Water-Deficit Stress in Cotton." International Journal of Plant Genomics 2015 (June 18, 2015): 1–11. http://dx.doi.org/10.1155/2015/892716.

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Cotton exhibits moderately high vegetative tolerance to water-deficit stress but lint production is restricted by the available rainfed and irrigation capacity. We have described the impact of water-deficit stress on the genetic and metabolic control of fiber quality and production. Here we examine the association of tentative consensus sequences (TCs) derived from various cotton tissues under irrigated and water-limited conditions with stress-responsive QTLs. Three thousand sixteen mapped sequence-tagged-sites were used as anchored targets to examine sequence homology with 15,784 TCs to test the hypothesis that putative stress-responsive genes will map within QTLs associated with stress-related phenotypic variation more frequently than with other genomic regions not associated with these QTLs. Approximately 1,906 of 15,784 TCs were mapped to the consensus map. About 35% of the annotated TCs that mapped within QTL regions were genes involved in an abiotic stress response. By comparison, only 14.5% of the annotated TCs mapped outside these QTLs were classified as abiotic stress genes. A simple binomial probability calculation of this degree of bias being observed if QTL and non-QTL regions are equally likely to contain stress genes was P(x ≥ 85)=7.99 × 10−15. These results suggest that the QTL regions have a higher propensity to contain stress genes.

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Lee, Young-Lim, Haruko Takeda, Gabriel Costa Monteiro Moreira, Latifa Karim, Erik Mullaart, Wouter Coppieters, Ruth Appeltant, et al. "A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle." PLOS Genetics 17, no. 7 (July 21, 2021): e1009331. http://dx.doi.org/10.1371/journal.pgen.1009331.

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Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a lead SNP, as a promising candidate variant. By implementing a fine-mapping and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits.

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Hwang, J. T. Gene, and Dan Nettleton. "Investigating the Probability of Sign Inconsistency in the Regression Coefficients of Markers Flanking Quantitative Trait Loci." Genetics 160, no. 4 (April 1, 2002): 1697–705. http://dx.doi.org/10.1093/genetics/160.4.1697.

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AbstractEstimates of the locations and effects of quantitative trait loci (QTL) can be obtained by regressing phenotype on marker genotype. Under certain basic conditions, the signs of regression coefficients flanking QTL must be the same. There is no guarantee, however, that the signs of the regression coefficient estimates will be the same. We use sign inconsistency to describe the situation in which there is disagreement between the signs of the estimated regression coefficients flanking QTL. The presence of sign inconsistency can undermine the effectiveness of QTL mapping strategies that presume intervals whose markers have regression coefficient estimates of differing sign to be devoid of QTL. This article investigates the likelihood of sign inconsistency under various conditions. We derive an analytic expression for the approximate probability of sign inconsistency in the single-QTL case. We also examine sign inconsistency probabilities when multiple QTL are present through simulation. We have discovered that the probability of sign inconsistency can be unacceptably high, even when the conditions for QTL detection are otherwise quite favorable.

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Serquen, Felix C., J. Bacher, and J. Staub. "A Linkage Map and QTL Analysis using RAPD Markers in a Narrow Cross in Cucumber (Cucumis sativus L.)." HortScience 31, no. 4 (August 1996): 601f—602. http://dx.doi.org/10.21273/hortsci.31.4.601f.

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Linkage maps in cucumber have been constructed in broad and narrow genetic base populations, using mostly RFLPs. RAPD markers are believed to be more advantageous than RFLPs for mapping in narrow crosses. An F3 population derived from F2 intercrossing cucumber inbred lines (G421 and H19) was used to construct a linkage map and to perform QTL analysis for horticultural traits recorded in two locations. One hundred three F3 families were used for mapping purpose. The parents were screened using ≈1500 primers yielding 80 RAPD markers that exhibited expected 3:1 Mendelian segregation. Additionally, female sex expression (F), little leaf (l), and determinate (de) loci also were evaluated in the segregating population. The linkage analysis and mapping was performed with MAPMAKER software, using a LOD score of 3.0 and recombination frequency of 0.40. QTL analysis was performed using one-way analysis of variance (ANOVA) and MAPMAKER/QTL. The linkage map integrates 83 map-points assembled into nine linkage groups. F and de loci mapped to linkage group `B', and the l locus was placed on linkage group `D'. The total map length is 628 cM, with an average distance between loci of 8.4 cM. Results from using one-way ANOVA and MAPMAKER/QTL had a good agreement for most QTL detected. Some QTL were location specific. Across locations four, one and three QTL were detected for sex expression, mainstem length, and number of laterals, respectively.

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Schumacher, Christina, Susanne Thümecke, Florian Schilling, Karin Köhl, Joachim Kopka, Heike Sprenger, Dirk Karl Hincha, et al. "Genome-Wide Approach to Identify Quantitative Trait Loci for Drought Tolerance in Tetraploid Potato (Solanum tuberosum L.)." International Journal of Molecular Sciences 22, no. 11 (June 7, 2021): 6123. http://dx.doi.org/10.3390/ijms22116123.

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Drought represents a major abiotic stress factor negatively affecting growth, yield and tuber quality of potatoes. Quantitative trait locus (QTL) analyses were performed in cultivated potatoes for drought tolerance index DRYM (deviation of relative starch yield from the experimental median), tuber starch content, tuber starch yield, tuber fresh weight, selected transcripts and metabolites under control and drought stress conditions. Eight genomic regions of major interest for drought tolerance were identified, three representing standalone DRYM QTL. Candidate genes, e.g., from signaling pathways for ethylene, abscisic acid and brassinosteroids, and genes encoding cell wall remodeling enzymes were identified within DRYM QTL. Co-localizations of DRYM QTL and QTL for tuber starch content, tuber starch yield and tuber fresh weight with underlying genes of the carbohydrate metabolism were observed. Overlaps of DRYM QTL with metabolite QTL for ribitol or galactinol may indicate trade-offs between starch and compatible solute biosynthesis. Expression QTL confirmed the drought stress relevance of selected transcripts by overlaps with DRYM QTL. Bulked segregant analyses combined with next-generation sequencing (BSAseq) were used to identify mutations in genes under the DRYM QTL on linkage group 3. Future analyses of identified genes for drought tolerance will give a better insight into drought tolerance in potatoes.

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Mrva, K., and D. J. Mares. "Quantitative trait locus analysis of late maturity a-amylase in wheat using the doubled haploid population Cranbrook Halberd." Australian Journal of Agricultural Research 52, no. 12 (2001): 1267. http://dx.doi.org/10.1071/ar01047.

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Mapping of the late maturity α-amylase (LMA) gene using quantitative trait locus (QTL) analysis represents an important step in identification of potential molecular markers that would greatly improve efficiency and accuracy of screening for LMA. QTL controlling the expression of LMA in wheat were detected in a doubled haploid (DH) cross/population derived from wheat (Triticum aestivum L. em. Thell) cultivars Cranbrook (LMA source) and Halberd (non-LMA). The DH population and parents were sown in replicated trials at Narrabri with sowing times differing by 2 weeks. Cool temperature treatment of detached tillers was used to induce expression of LMA in lines carrying the defect. The number of grains in ripe, treated tillers that contained high pI (malt, germination type) α-amylase isozymes was measured using an ELISA antibody kit highly specific for high pI isozymes. QTL analyses were conducted separately for each sowing, but results from both sowings were consistent and indicated that there was a highly significant (P < 0.001) QTL on the long arm of chromosome 7B (accounting for 31% of the variation in the first experiment), with Cranbrook contributing the higher value allele. A second QTL that accounted for 13% of the variation was found close to the centromere on chromosome 3B. Although it was less important than the QTL on 7B it was nevertheless still significant (P < 0.05).

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EL Hassouni, Khaoula, Malte Sielaff, Valentina Curella, Manjusha Neerukonda, Willmar Leiser, Tobias Würschum, Detlef Schuppan, Stefan Tenzer, and C. Friedrich H. Longin. "Genetic architecture underlying the expression of eight α-amylase trypsin inhibitors." Theoretical and Applied Genetics 134, no. 10 (July 10, 2021): 3427–41. http://dx.doi.org/10.1007/s00122-021-03906-y.

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Abstract Key message Wheat cultivars largely differ in the content and composition of ATI proteins, but heritability was quite low for six out of eight ATIs. The genetic architecture of ATI proteins is built up of few major and numerous small effect QTL. Abstract Amylase trypsin inhibitors (ATIs) are important allergens in baker’s asthma and suspected triggers of non-celiac wheat sensitivity (NCWS) inducing intestinal and extra-intestinal inflammation. As studies on the expression and genetic architecture of ATI proteins in wheat are lacking, we evaluated 149 European old and modern bread wheat cultivars grown at three different field locations for their content of eight ATI proteins. Large differences in the content and composition of ATIs in the different cultivars were identified ranging from 3.76 pmol for ATI CM2 to 80.4 pmol for ATI 0.19, with up to 2.5-fold variation in CM-type and up to sixfold variation in mono/dimeric ATIs. Generally, heritability estimates were low except for ATI 0.28 and ATI CM2. ATI protein content showed a low correlation with quality traits commonly analyzed in wheat breeding. Similarly, no trends were found regarding ATI content in wheat cultivars originating from numerous countries and decades of breeding history. Genome-wide association mapping revealed a complex genetic architecture built of many small, few medium and two major quantitative trait loci (QTL). The major QTL were located on chromosomes 3B for ATI 0.19-like and 6B for ATI 0.28, explaining 70.6 and 68.7% of the genotypic variance, respectively. Within close physical proximity to the medium and major QTL, we identified eight potential candidate genes on the wheat reference genome encoding structurally related lipid transfer proteins. Consequently, selection and breeding of wheat cultivars with low ATI protein amounts appear difficult requiring other strategies to reduce ATI content in wheat products.

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Lyons, Malcolm A., Henning Wittenburg, Renhua Li, Kenneth A. Walsh, Monika R. Leonard, Gary A. Churchill, Martin C. Carey, and Beverly Paigen. "New quantitative trait loci that contribute to cholesterol gallstone formation detected in an intercross of CAST/Ei and 129S1/SvImJ inbred mice." Physiological Genomics 14, no. 3 (August 15, 2003): 225–39. http://dx.doi.org/10.1152/physiolgenomics.00073.2003.

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Cholesterol gallstone formation is a response to interactions between multiple genes and environmental stimuli. To determine the subset of cholesterol gallstone susceptibility ( Lith) genes possessed by strains CAST/Ei (susceptible) and 129S1/SvImJ (resistant), we conducted quantitative trait locus (QTL) analyses of an intercross between these strains. Parental strains and F1 mice of both genders were evaluated for gallstone formation after consumption of a lithogenic diet for 8 wk. Gallstone susceptibility of strain CAST was predominantly due to cholesterol hypersecretion. Male intercross offspring were genotyped and phenotyped for cholesterol gallstone formation after consumption of the lithogenic diet for 10 wk. Linkage analysis was performed using PSEUDOMARKER software. One significant, new QTL was detected and named Lith13 [chromosome (Chr) 5, 30 cM]. Statistical analyses and QTL fine mapping suggest this QTL may comprise two closely linked loci. We confirmed the presence of Lith6 (Chr 6). Suggestive QTL were detected on Chrs 1, 2, 5, 14, and 16. The QTL on Chrs 2 and 16 confirmed previously identified, suggestive QTL. Therefore, they were named Lith12 (101 cM) and Lith14 (42 cM), respectively. We identified candidate genes based on known function and location and performed mRNA expression analyses using both parental strains and intercross progeny for preliminary evaluation of their contributions to gallstone formation. Cebpb ( Lith12), Pparg ( Lith6), and Slc21a1 ( Lith6) displayed expression differences. Our work continues to demonstrate the genetic complexity and to elucidate the pathophysiology of cholesterol gallstone formation. It should facilitate the development of new approaches for treating this common human disorder.

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Grattapaglia, Dario, Fernando L. G. Bertolucci, Ricardo Penchel, and Ronald R. Sederoff. "Genetic Mapping of Quantitative Trait Loci Controlling Growth and Wood Quality Traits in Eucalyptus grandis Using a Maternal Half-sib Family and RAPD Markers." Genetics 144, no. 3 (November 1, 1996): 1205–14. http://dx.doi.org/10.1093/genetics/144.3.1205.

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Abstract 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.

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Barkalifa, Ronit, Yoram Yagil, and Chana Yagil. "Sex-specific genetic dissection of diabetes in a rodent model identifies Ica1 and Ndufa4 as major candidate genes." Physiological Genomics 42, no. 3 (August 2010): 445–55. http://dx.doi.org/10.1152/physiolgenomics.00042.2010.

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The aim of the study was to initiate a sex-specific investigation of the molecular basis of diabetes, using a genomic approach in the Cohen Diabetic rat model of diet-induced Type 2 diabetes. We used an F2 population resulting from a cross between Cohen Diabetic susceptible (CDs) and resistant (CDr) and consisting of 132 males and 159 females to detect relevant QTLs by linkage and cosegregation analyses. To confirm the functional relevance of the QTL, we applied the “chromosome substitution” strategy. We identified candidate genes within the quantitative trait locus (QTL) and studied their differential expression. We sequenced the differentially expressed candidate genes to account for differences in their expression. We confirmed in this new cross in males a previously detected major QTL on rat chromosome 4 (RNO4); we identified in females this major QTL as well. We found three additional diabetes-related QTLs on RNO11, 13, and 20 in females only. We pursued the investigation of the QTL on RNO4 and generated a CDs.4CDr consomic strain, which provided us with functional confirmation for the contribution of the QTL to the diabetic phenotype in both sexes. We successfully narrowed the QTL span to 2.6 cM and identified within it six candidate genes, but only two of which, Ica1 (islet cell autoantigen 1) and Ndufa4 (NADH dehydrogenase ubiquinone) were differentially expressed between CDs and CDr. We sequenced the exons and promoter regions of Ica1 and Ndufa4 but did not identify sequence variations between the strains. The detection of the QTL on RNO4 in both sexes suggests involvement of Ica1, Ndufa4, the Golgi apparatus, the mitochondria and genetic susceptibility to dietary-environmental factors in the pathophysiology of diabetes in our model. The additional sex-specific QTLs are likely to account for differences in the diabetic phenotype between the sexes.

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Kelly, Scott A., Derrick L. Nehrenberg, Kunjie Hua, Theodore Garland, and Daniel Pomp. "Quantitative genomics of voluntary exercise in mice: transcriptional analysis and mapping of expression QTL in muscle." Physiological Genomics 46, no. 16 (August 15, 2014): 593–601. http://dx.doi.org/10.1152/physiolgenomics.00023.2014.

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Motivation and ability both underlie voluntary exercise, each with a potentially unique genetic architecture. Muscle structure and function are one of many morphological and physiological systems acting to simultaneously determine exercise ability. We generated a large ( n = 815) advanced intercross line of mice (G4) derived from a line selectively bred for increased wheel running (high runner) and the C57BL/6J inbred strain. We previously mapped quantitative trait loci (QTL) contributing to voluntary exercise, body composition, and changes in body composition as a result of exercise. Using brain tissue in a subset of the G4 ( n = 244), we have also previously reported expression QTL (eQTL) colocalizing with the QTL for the higher-level phenotypes. Here, we examined the transcriptional landscape of hind limb muscle tissue via global mRNA expression profiles. Correlations revealed an ∼1,168% increase in significant relationships between muscle transcript expression levels and the same exercise and body composition phenotypes examined previously in the brain. The exercise trait most often significantly correlated with gene expression in the brain was running duration while in the muscle it was maximum running speed. This difference may indicate that time spent engaging in exercise behavior may be more influenced by central (neurobiological) mechanisms, while intensity of exercise may be largely controlled by peripheral mechanisms. Additionally, we used subsets of cis-acting eQTL, colocalizing with QTL, to identify candidate genes based on both positional and functional evidence. We discuss three plausible candidate genes ( Insig2, Prcp, Sparc) and their potential regulatory role.

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Vergne, E., E. Ballini, G. Droc, D. Tharreau, J. L. Nottéghem, and J. B. Morel. "ARCHIPELAGO: A Dedicated Resource for Exploiting Past, Present, and Future Genomic Data on Disease Resistance Regulation in Rice." Molecular Plant-Microbe Interactions® 21, no. 7 (July 2008): 869–78. http://dx.doi.org/10.1094/mpmi-21-7-0869.

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Large amounts of expression data dealing with biotic stresses in rice have been produced in the past 5 years. Here, we extensively review approximately 70 publications and gather together information on more than 2,500 genes of the rice defense arsenal. This information was integrated into the OryGenesDB database. Several genes (e.g., metallothioneins and PBZ1) appear to be hallmarks of rice–pathogen interactions. Cross-referencing this information with the rice kinome highlighted some defense genes and kinases as possible central nodes of regulation. Cross referencing defense gene expression and quantitative trait loci (QTL) information identified some candidate genes for QTL. Overall, pathogenesis-related genes and disease regulators were found to be statistically associated with disease QTL. At the genomic level, we observed that some regions are richer than others and that some chromosomes (e.g., 11 and 12), which contain a lot of resistance gene analogs, have a low content of defense genes. Finally, we show that classical defense genes and defense-related genes such as resistance genes are preferentially organized in clusters. These clusters are not always coregulated and individual paralogs can show specific expression patterns. Thus, the rice defense arsenal has an ARCHIPELAGO-like genome structure at the macro and micro level. This resource opens new possibilities for marker-assisted selection and QTL cloning.

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JinQuan, Li, and Zhang WenGuang. "Expression Sequence Tag and QTL/MAS of Goat/Sheep in China." Recent Patents on DNA & Gene Sequences 3, no. 3 (November 1, 2009): 213–18. http://dx.doi.org/10.2174/187221509789318379.

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Zhang, W., E. R. Gamazon, X. Zhang, A. Konkashbaev, C. Liu, K. L. Szilagyi, M. E. Dolan, and N. J. Cox. "SCAN database: facilitating integrative analyses of cytosine modification and expression QTL." Database 2015 (March 27, 2015): bav025. http://dx.doi.org/10.1093/database/bav025.

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Zhang, Jizhun, Kewei Jiang, Zhanlong Shen, Zhidong Gao, Liang Lv, Yingjiang Ye, and Shan Wang. "Expression QTL-based analyses reveal the mechanisms underlying colorectal cancer predisposition." Tumor Biology 35, no. 12 (September 10, 2014): 12607–11. http://dx.doi.org/10.1007/s13277-014-2583-8.

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Norman, Joseph D., Moira M. Ferguson, and Roy G. Danzmann. "Transcriptomics of salinity tolerance capacity in Arctic charr (Salvelinus alpinus): a comparison of gene expression profiles between divergent QTL genotypes." Physiological Genomics 46, no. 4 (February 15, 2014): 123–37. http://dx.doi.org/10.1152/physiolgenomics.00105.2013.

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Osmoregulatory capabilities have played an important role in the evolution, dispersal, and diversification of vertebrates. To better understand the genetic architecture of hypo-osmoregulation in fishes and to determine which genes and biological processes affect intraspecific variation in salinity tolerance, we used mRNA sequence libraries from Arctic charr gill tissue to compare gene expression profiles in fish exhibiting divergent salinity tolerance quantitative trait locus (QTL) genotypes. We compared differentially expressed genes with QTL positions to gain insight about the nature of the underlying polymorphisms and examined gene expression within the context of genome organization to gain insight about the evolution of hypo-osmoregulation in fishes. mRNA sequencing of 18 gill tissue libraries produced 417 million reads, and the final reduced de novo transcriptome assembly consisted of 92,543 contigs. Families contained a similar number of differentially expressed contigs between high and low salinity tolerance capacity groups, and log2 expression ratios ranged from 10.4 to −8.6. We found that intraspecific variation in salinity tolerance capacity correlated with differential expression of immune response genes. Some differentially expressed genes formed clusters along linkage groups. Most clusters comprised gene pairs, though clusters of three, four, and eight genes were also observed. We postulated that conserved synteny of gene clusters on multiple ancestral and teleost chromosomes may have been preserved via purifying selection. Colocalization of QTL with differentially expressed genes suggests that polymorphisms in cis-regulatory elements are part of a majority of QTL.

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Lark, K. G., J. Orf, and L. M. Mansur. "Epistatic expression of quantitative trait loci (QTL) in soybean [Glycine max (L.) Merr.] determined by QTL association with RFLP alleles." Theoretical and Applied Genetics 88-88, no. 3-4 (June 1994): 486–89. http://dx.doi.org/10.1007/bf00223665.

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Heidari, Bahram, Badraldin Ebrahim Sayed-Tabatabaei, Ghodratollah Saeidi, Michael Kearsey, and Kazuhiro Suenaga. "Mapping QTL for grain yield, yield components, and spike features in a doubled haploid population of bread wheat." Genome 54, no. 6 (June 2011): 517–27. http://dx.doi.org/10.1139/g11-017.

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A doubled haploid (DH) population derived from a cross between the Japanese cultivar ‘Fukuho-kumogi’ and the Israeli wheat line ‘Oligoculm’ was used to map genome regions involved in the expression of grain yield, yield components, and spike features in wheat (Triticum aestivum L). A total of 371 markers (RAPD, SSR, RFLP, AFLP, and two morphological traits) were used to construct the linkage map that covered 4190 cM of wheat genome including 28 linkage groups. The results of composite interval mapping for all studied traits showed that some of the quantitative trait loci (QTL) were stable over experiments conducted in 2004 and 2005. The major QTL located in the Hair–Xpsp2999 interval on chromosome 1A controlled the expression of grains/spike (R2 = 12.9% in 2004 and 22.4% in 2005), grain weight/spike (R2 = 21.4% in 2004 and 15.8% in 2005), and spike number (R2 = 15.6% in 2004 and 5.4% in 2005). The QTL for grain yield located on chromosomes 6A, 6B, and 6D totally accounted for 27.2% and 31.7% of total variation in this trait in 2004 and 2005, respectively. Alleles inherited from ‘Oligoculm’ increased the length of spikes and had decreasing effects on spike number. According to the data obtained in 2005, locus Xgwm261 was associated with a highly significant spike length QTL (R2 = 42.33%) and also the major QTL for spikelet compactness (R2 = 26.1%).

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Sheehan, Susan, Shirng-Wern Tsaih, Benjamin L. King, Caitlin Stanton, Gary A. Churchill, Beverly Paigen, and Keith DiPetrillo. "Genetic analysis of albuminuria in a cross between C57BL/6J and DBA/2J mice." American Journal of Physiology-Renal Physiology 293, no. 5 (November 2007): F1649—F1656. http://dx.doi.org/10.1152/ajprenal.00233.2007.

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Chronic kidney disease (CKD) is a growing medical problem and a significant risk factor for the development of end-stage renal disease, cardiovascular disease, and cardiovascular mortality. The genetic basis of CKD is recognized, but knowledge of the specific genes that contribute to the onset and progression of kidney disease is limited, mainly because of the difficulty and expense of identifying genes underlying CKD in humans. Results from genetic studies of CKD in rodents often correspond to findings in humans; therefore, we used quantitative trait locus (QTL) analysis to detect genomic regions affecting albuminuria in a cross between C57BL/6J and DBA/2J mice, strains resistant and susceptible to CKD, respectively. We identified several independent and interacting loci affecting albuminuria, including one QTL on mouse chromosome (Chr) 2 that is concordant with QTL influencing urinary albumin excretion on rat Chr 3 and diabetic nephropathy on human Chr 20p. Because this QTL was identified in multiple mouse crosses, as well as in rats and in humans, we used comparative genomics, haplotype analysis, and expression profiling to narrow the initial QTL interval from 386 genes to 10 genes with known coding sequence polymorphisms or expression differences between the strains. These results support the continued use of multiple cross-mapping and cross-species comparisons to further our understanding of the genetic basis of kidney disease.

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Diepenbrock, Christine H., Daniel C. Ilut, Maria Magallanes-Lundback, Catherine B. Kandianis, Alexander E. Lipka, Peter J. Bradbury, James B. Holland, et al. "Eleven biosynthetic genes explain the majority of natural variation in carotenoid levels in maize grain." Plant Cell 33, no. 4 (December 2, 2020): 882–900. http://dx.doi.org/10.1093/plcell/koab032.

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Abstract Vitamin A deficiency remains prevalent in parts of Asia, Latin America, and sub-Saharan Africa where maize (Zea mays) is a food staple. Extensive natural variation exists for carotenoids in maize grain. Here, to understand its genetic basis, we conducted a joint linkage and genome-wide association study of the US maize nested association mapping panel. Eleven of the 44 detected quantitative trait loci (QTL) were resolved to individual genes. Six of these were correlated expression and effect QTL (ceeQTL), showing strong correlations between RNA-seq expression abundances and QTL allelic effect estimates across six stages of grain development. These six ceeQTL also had the largest percentage of phenotypic variance explained, and in major part comprised the three to five loci capturing the bulk of genetic variation for each trait. Most of these ceeQTL had strongly correlated QTL allelic effect estimates across multiple traits. These findings provide an in-depth genome-level understanding of the genetic and molecular control of carotenoids in plants. In addition, these findings provide a roadmap to accelerate breeding for provitamin A and other priority carotenoid traits in maize grain that should be readily extendable to other cereals.

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Ma, Yu, Afef Marzougui, Clarice J. Coyne, Sindhuja Sankaran, Dorrie Main, Lyndon D. Porter, Deus Mugabe, et al. "Dissecting the Genetic Architecture of Aphanomyces Root Rot Resistance in Lentil by QTL Mapping and Genome-Wide Association Study." International Journal of Molecular Sciences 21, no. 6 (March 20, 2020): 2129. http://dx.doi.org/10.3390/ijms21062129.

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Lentil (Lens culinaris Medikus) is an important source of protein for people in developing countries. Aphanomyces root rot (ARR) has emerged as one of the most devastating diseases affecting lentil production. In this study, we applied two complementary quantitative trait loci (QTL) analysis approaches to unravel the genetic architecture underlying this complex trait. A recombinant inbred line (RIL) population and an association mapping population were genotyped using genotyping by sequencing (GBS) to discover novel single nucleotide polymorphisms (SNPs). QTL mapping identified 19 QTL associated with ARR resistance, while association mapping detected 38 QTL and highlighted accumulation of favorable haplotypes in most of the resistant accessions. Seven QTL clusters were discovered on six chromosomes, and 15 putative genes were identified within the QTL clusters. To validate QTL mapping and genome-wide association study (GWAS) results, expression analysis of five selected genes was conducted on partially resistant and susceptible accessions. Three of the genes were differentially expressed at early stages of infection, two of which may be associated with ARR resistance. Our findings provide valuable insight into the genetic control of ARR, and genetic and genomic resources developed here can be used to accelerate development of lentil cultivars with high levels of partial resistance to ARR.

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Lana, Ubiraci Gomes de Paula, Isabel Regina Prazeres de Souza, Roberto Willians Noda, Maria Marta Pastina, Jurandir Vieira Magalhaes, and Claudia Teixeira Guimaraes. "Quantitative Trait Loci and Resistance Gene Analogs Associated with Maize White Spot Resistance." Plant Disease 101, no. 1 (January 2017): 200–208. http://dx.doi.org/10.1094/pdis-06-16-0899-re.

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Maize white spot (MWS), caused by the bacterium Pantoea ananatis, is one of the most important maize foliar diseases in tropical and subtropical regions, causing significant yield losses. Despite its economic importance, genetic studies of MWS are scarce. The aim of this study was to map quantitative trait loci (QTL) associated with MWS resistance and to identify resistance gene analogs (RGA) underlying these QTL. QTL mapping was performed in a tropical maize F2:3 population, which was genotyped with simple-sequence repeat and RGA-tagged markers and phenotyped for the response to MWS in two Brazilian southeastern locations. Nine QTL explained approximately 70% of the phenotypic variance for MWS resistance at each location, with two of them consistently detected in both environments. Data mining using 112 resistance genes cloned from different plant species revealed 1,697 RGA distributed in clusters within the maize genome. The RGA Pto19, Pto20, Pto99, and Xa26.151.4 were genetically mapped within MWS resistance QTL on chromosomes 4 and 8 and were preferentially expressed in the resistant parental line at locations where their respective QTL occurred. The consistency of QTL mapping, in silico prediction, and gene expression analyses revealed RGA and genomic regions suitable for marker-assisted selection to improve MWS resistance.

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Tan, M. K., A. P. Verbyla, B. R. Cullis, P. Martin, A. W. Milgate, and J. R. Oliver. "Genetics of late maturity α-amylase in a doubled haploid wheat population." Crop and Pasture Science 61, no. 2 (2010): 153. http://dx.doi.org/10.1071/cp09239.

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Late maturity α-amylase (LMA) in wheat is a defect where high-isoelectric point (pI) α-amylase accumulates in the ripening grain. Wheat genotypes vary in expression from zero to high levels of α-amylase, the latter with detrimental consequences on their use for value-added end products. Expression in each genotype is characterised by varying numbers of grains affected and different levels in each grain. Analysis of a doubled haploid (DH) population (188 lines) from WW1842 × Whistler has identified significant QTL on chromosomes 2DL, 3A, 3B, 3D, 4B, 4D, 5DS and 5BL. The 4B LMA allele (P < 0.0001) from Whistler is closely linked to the QTL for the ‘tall’ allele (P < 0.0001) of the Rht-B1 gene. The 4D LMA QTL (P < 0.0001) in WW1842 co-locates with the QTL for the ‘tall’ allele (P < 0.0001) of the Rht-D1 gene. This study has shown for the first time that a DH cross between two semi-dwarf cultivars with low or no LMA produces ~25% of progeny lines of the ‘tall’ genotypes with a high frequency of LMA. This is attributed to the large additive positive effects from the combination of one recessive ‘tall’ Rht-B1 gene and one recessive ‘tall’ Rht-D1 gene. High-yielding semi-dwarf genotypes with different combinations of Rht-B1 and Rht-D1 alleles which have very low or non-existent LMA expression (e.g. WW1842 and Whistler) may meet industry criteria for registration as commercial wheat varieties. However, when they are used as breeding lines, the cross produces some progeny genotypes with severe levels of LMA. These LMA genotypes comprise the gibberellic acid-sensitive ‘tall’ progenies and a very small proportion of semi-dwarfs. Thus, it is of paramount importance to screen the defect in wheat breeding programs. The suite of QTL identified for LMA will enable the use of marker assisted selection in the pyramiding of the beneficial QTL to maximise yield and minimise (or eliminate) LMA in semi-dwarf genotypes.

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Das, Samarendra, and Shesh N. Rai. "Statistical Approach of Gene Set Analysis with Quantitative Trait Loci for Crop Gene Expression Studies." Entropy 23, no. 8 (July 23, 2021): 945. http://dx.doi.org/10.3390/e23080945.

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Genome-wide expression study is a powerful genomic technology to quantify expression dynamics of genes in a genome. In gene expression study, gene set analysis has become the first choice to gain insights into the underlying biology of diseases or stresses in plants. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results from the primary downstream differential expression analysis. The gene set analysis approaches are well developed in microarrays and RNA-seq gene expression data analysis. These approaches mainly focus on analyzing the gene sets with gene ontology or pathway annotation data. However, in plant biology, such methods may not establish any formal relationship between the genotypes and the phenotypes, as most of the traits are quantitative and controlled by polygenes. The existing Quantitative Trait Loci (QTL)-based gene set analysis approaches only focus on the over-representation analysis of the selected genes while ignoring their associated gene scores. Therefore, we developed an innovative statistical approach, GSQSeq, to analyze the gene sets with trait enriched QTL data. This approach considers the associated differential expression scores of genes while analyzing the gene sets. The performance of the developed method was tested on five different crop gene expression datasets obtained from real crop gene expression studies. Our analytical results indicated that the trait-specific analysis of gene sets was more robust and successful through the proposed approach than existing techniques. Further, the developed method provides a valuable platform for integrating the gene expression data with QTL data.

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Yi, Nengjun, and Shizhong Xu. "Bayesian Mapping of Quantitative Trait Loci for Complex Binary Traits." Genetics 155, no. 3 (July 1, 2000): 1391–403. http://dx.doi.org/10.1093/genetics/155.3.1391.

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AbstractA complex binary trait is a character that has a dichotomous expression but with a polygenic genetic background. Mapping quantitative trait loci (QTL) for such traits is difficult because of the discrete nature and the reduced variation in the phenotypic distribution. Bayesian statistics are proved to be a powerful tool for solving complicated genetic problems, such as multiple QTL with nonadditive effects, and have been successfully applied to QTL mapping for continuous traits. In this study, we show that Bayesian statistics are particularly useful for mapping QTL for complex binary traits. We model the binary trait under the classical threshold model of quantitative genetics. The Bayesian mapping statistics are developed on the basis of the idea of data augmentation. This treatment allows an easy way to generate the value of a hypothetical underlying variable (called the liability) and a threshold, which in turn allow the use of existing Bayesian statistics. The reversible jump Markov chain Monte Carlo algorithm is used to simulate the posterior samples of all unknowns, including the number of QTL, the locations and effects of identified QTL, genotypes of each individual at both the QTL and markers, and eventually the liability of each individual. The Bayesian mapping ends with an estimation of the joint posterior distribution of the number of QTL and the locations and effects of the identified QTL. Utilities of the method are demonstrated using a simulated outbred full-sib family. A computer program written in FORTRAN language is freely available on request.

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Kumar, K. Ganesh, Lauri O. Byerley, Julia Volaufova, Daniel J. Drucker, Gary A. Churchill, Renhua Li, Barbara York, Aamir Zuberi, and Brenda K. Smith Richards. "Genetic variation in Glp1r expression influences the rate of gastric emptying in mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 294, no. 2 (February 2008): R362—R371. http://dx.doi.org/10.1152/ajpregu.00640.2007.

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We demonstrated previously that food intake traits map to a quantitative trait locus (QTL) on proximal chromosome 17, which encompasses Glp1r (glucagon-like peptide 1 receptor), encoding an important modulator of gastric emptying. We then confirmed this QTL in a B6.CAST-17 congenic strain that consumed 27% more carbohydrate and 17% more total calories, yet similar fat calories, per body weight compared with the recipient C57BL/6J. The congenic strain also consumed greater food volume. The current aims were to 1) identify genetic linkage for total food volume in F2 mice, 2) perform gene expression profiling in stomach of B6.CAST-17 congenic mice using oligonucleotide arrays, 3) test for allelic imbalance in Glp1r expression, 4) evaluate gastric emptying rate in parental and congenic mice, and 5) investigate a possible effect of genetic variation in Glp1r on gastric emptying. A genome scan revealed a single QTL for total food volume ( Tfv1) (log of the odds ratio = 7.6), which was confirmed in B6.CAST-17 congenic mice. Glp1r exhibited allelic imbalance in stomach, which correlated with accelerated gastric emptying in parental CAST and congenic B6.CAST-17 mice. Moreover, congenic mice displayed an impaired gastric emptying response to exendin-(9-39). These results suggest that genetic variation in Glp1r contributes to the strain differences in gastric emptying rate.

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Adewoye, Adeolu B., Sergey V. Nuzhdin, and Eran Tauber. "Mapping Quantitative Trait Loci Underlying Circadian Light Sensitivity in Drosophila." Journal of Biological Rhythms 32, no. 5 (October 2017): 394–405. http://dx.doi.org/10.1177/0748730417731863.

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Despite the significant advance in our understanding of the molecular basis of light entrainment of the circadian clock in Drosophila, the underlying genetic architecture is still largely unknown. The aim of this study was to identify loci associated with variation in circadian photosensitivity, which are important for the evolution of this trait. We have used complementary approaches that combined quantitative trait loci (QTL) mapping, complementation testing, and transcriptome profiling to dissect this variation. We identified a major QTL on chromosome 2, which was subsequently fine mapped using deficiency complementation mapping into 2 smaller regions spanning 139 genes, some of which are known to be involved in functions that have been previously implicated in light entrainment. Two genes implicated with the clock and located within that interval, timeless and cycle, failed to complement the QTL, indicating that alleles of these genes contribute to the variation in light response. Specifically, we find that the timeless s/ ls polymorphism that has been previously shown to constitute a latitudinal cline in Europe is also segregating in our recombinant inbred lines and is contributing to the phenotypic variation in light sensitivity. We also profiled gene expression in 2 recombinant inbred strains that differ significantly in their photosensitivity and identified a total of 368 transcripts that showed differential expression (false discovery rate < 0.1). Of 131 transcripts that showed a significant recombinant inbred line by treatment interaction (i.e., putative expression QTL), 4 are located within QTL2.

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HONKATUKIA, M., M. TUISKULA-HAAVISTO, and J. VILKKI. "Chromosome regions affecting body weight in egg layers." Agricultural and Food Science 16, no. 2 (December 4, 2008): 177. http://dx.doi.org/10.2137/145960607782219355.

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We have previously mapped quantitative trait loci (QTL) affecting egg production and quality traits using a reciprocal cross of two divergent egg-layer lines. The lines differ also in body weight, and we initially identified genome-wide significant Mendelian QTL for adult body weight at 40 weeks of age and feed intake at 3236 weeks of age. In addition, QTL with parent-of-origin effects were detected for feed intake and body weight. In the present study, a total of five body weight traits (weight at 16, 20, 24, 40 and 60 weeks of age) have been analysed in the same mapping population. New QTL affecting body weight at different ages were found on chromosomes 1, 4, 5, 6, and 13. Both Mendelian QTL and loci with parent-of-origin expression were found. Our findings are in good agreement with the results of previous studies on different mapping populations. The results elucidate the most important chromosome regions affecting weight in poultry in general and may add to the understanding of such loci among domestic animals.;

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Journal articles on the topic 'Expression QTL'

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