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Results for “expression quantitative trait loci”

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PubMed2005

A QTL resource and comparison tool for pigs: PigQTLDB.

During the past decade, efforts to map quantitative trait loci (QTL) in pigs have resulted in hundreds of QTL being reported for growth, meat quality, reproduction, disease resistance, and other traits. It is a challenge to locate, interpret, and compare QTL results from different studies. We have developed a pig QTL database (PigQTLdb) that integrates available pig QTL data in the public domain, thus, facilitating the use of this QTL data in future studies. We also developed a pig trait classification system to standardize names of traits and to simplify organization and searching of the trait data. These steps made it possible to compare primary data from diverse sources and methods. We used existing pig map databases and other publicly available data resources (such as PubMed) to avoid redundant developmental work. The PigQTLdb was also designed to include data representing major genes and markers associated with a large effect on economically important traits. To date, over 790 QTL from 73 publications have been curated into the database. Those QTL cover more than 300 different traits. The data have been submitted to the Entrez Gene and the Map Viewer resources at NCBI, where the information about markers was matched to marker records in NCBI's UniSTS database. Having these data in a public resource like NCBI allows regularly updated automatic matching of markers to public sequence data by e-PCR. The submitted data, and the results of these calculations, are retrievable from NCBI via Entrez Gene, Map Viewer, and UniSTS. Efforts were undertaken to improve the integrated functional genomics resources for pigs.

Animals↗

PubMed2002

Analyses of differential gene expression in genetic hypertensive rats by microarray.

We identified genes that were differentially expressed between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using cDNA microarray analysis, and analyzed the correlation between these genes and hypertension. Twenty four genes were found to be up-regulated and 20 were down-regulated in SHR. We selected 11 genes (6 up-regulated genes: SAH, Hsp70, MCT1, RBP, IDI1, Prion; and 5 down-regulated genes: Thrombin, Dyn, SOD3, Ela1, Gst Y(b)) and subjected them to an F2 cosegregation analysis. One hundred five F2 rats were obtained from the same strains used for microarray analysis, and blood pressure was measured directly with a catheter implanted in the femoral artery. The genotypes of monocarboxylate transporter 1 and glutathione S-transferase Y(b) subunit significantly affected diastolic blood pressure in F2 rats, and these two genes are located near each other on chromosome 2. However, quantitative trait loci (QTL) analysis in this region revealed that the QTL for diastolic blood pressure were from these two genes. Antihypertensive treatment with either enalapril or hydralazine only affected the expression level of Hsp70, which was up-regulated by hydralazine, probably through compensatory sympathetic activation. We were unable to associate the other 10 genes with hypertension in SHR. Based on these results, the identification of differentially expressed genes may not be an efficient method for selecting candidate genes for hypertension in the SHR-WKY system.

Animals↗

PubMed2006

Natural genetic variation in whole-genome expression in Arabidopsis thaliana: the impact of physiological QTL introgression.

A long-standing and fundamental question in biology is how genes influence complex phenotypes. Combining near-isogenic line mapping with genome expression profiling offers a unique opportunity for exploring the functional relationship between genotype and phenotype and for generating candidate genes for future study. We used a whole-genome microarray produced with ink-jet technology to measure the relative expression level of over 21,500 genes from an Arabidopsis thaliana near-isogenic line (NIL) and its recurrent parent. The NIL material contained two introgressions (bottom of chromosome II and top of chromosome III) of the Cvi-1 ecotype in a Ler-2 ecotype genome background. Each introgression 'captures' a Cvi allele of a physiological quantitative trait loci (QTL) that our previous studies have shown increases transpiration and reduces water-use efficiency at the whole-plant level. We used a mixed model anova framework for assessing sources of expression variability and for evaluating statistical significance in our array experiment. We discovered 25 differentially expressed genes in the introgression at a false-discovery rate (FDR) cut-off of 0.20 and identified new candidate genes for both QTL regions. Several differentially expressed genes were confirmed with QRT-PCR (quantitative reverse transcription-polymerase chain reaction) assays. In contrast, we found no statistically significant differentially expressed genes outside of the QTL introgressions after controlling for multiple tests. We discuss these results in the context of candidate genes, cloning QTL, and phenotypic evolution.

Arabidopsis↗

PubMed2004

Coordinated genetic regulation of growth and lignin revealed by quantitative trait locus analysis of cDNA microarray data in an interspecific backcross of eucalyptus.

Phenotypic, genotypic, and transcript level (microarray) data from an interspecific backcross population of Eucalyptus grandis and Eucalyptus globulus were integrated to dissect the genetic and metabolic network underlying growth variation. Transcript abundance, measured for 2,608 genes in the differentiating xylem of a 91 (E. grandis x E. globulus) x E. grandis backcross progeny was correlated with diameter variation, revealing coordinated down-regulation of genes encoding enzymes of the lignin biosynthesis and associated methylation pathways in fast growing individuals. Lignin analysis of wood samples confirmed the content and quality predicted by the transcript levels measured on the microarrays. Quantitative trait locus (QTL) analysis of transcript levels of lignin-related genes showed that their mRNA abundance is regulated by two genetic loci, demonstrating coordinated genetic control over lignin biosynthesis. These two loci colocalize with QTLs for growth, suggesting that the same genomic regions are regulating growth, and lignin content and composition in the progeny. Genetic mapping of the lignin genes revealed that most of the key biosynthetic genes do not colocalize with growth and transcript level QTLs, with the exception of the locus encoding the enzyme S-adenosylmethionine synthase. This study illustrates the power of integrating quantitative analysis of gene expression data and genetic map information to discover genetic and metabolic networks regulating complex biological traits. (Sequence data for this article have been deposited with the EMBL/GenBank data libraries under accession numbers CB 967505 to CB 968059; CD 667988 to CD 670002; CD 670004; CD 670097; CD 670101 to CD 670112; and CD 670114 to CD 670137.)

Base Sequence↗

PubMed2003

Which genetic loci have greater population assignment power?

SUMMARY: WHICHLOCI is a program that determines the relative discriminatory power of alternate genetic loci and loci combinations for population assignment of individuals. AVAILABILITY: http://www.oregonstate.edu/dept/comes/genetics/software.htm

Algorithms↗

PubMed2005

Genetic dissection of neurodegeneration and CNS inflammation.

Inflammation and neurodegeneration characterize multiple sclerosis, as well as many other diseases of the central nervous system (CNS). The understanding of the molecular pathways that regulate these processes is of fundamental importance for the development of new therapies. Nerve lesions paradigms in animals can serve as important tools to dissect central features of human CNS disease and by using these models certain key regulators have also been identified. However, our knowledge of how aspects of neurodegeneration and CNS inflammation are regulated on a genomic level is very limited. Such knowledge may help to unravel disease mechanisms. By using a standardized nerve trauma model, ventral root avulsion (VRA), in a series of inbred rat strains we here demonstrate a potent genetic regulation of the degree of neuron death and glial activation. Genome wide mapping of these phenotypes in experimental rat strain crosses identifies several quantitative trait loci (QTLs) controlling nerve lesion-induced nerve cell death, local T cell accumulation and expression of MHC class II on microglia. This approach may lead to the identification of evolutionary conserved genetic polymorphisms in key controlling genes, which can serve as prime candidates for association studies in several human CNS diseases.

Animals↗

PubMed2006

Sorghum stay-green QTL individually reduce post-flowering drought-induced leaf senescence.

Sorghum is an important source of food, feed, and biofuel, especially in the semi-arid tropics because this cereal is well adapted to harsh, drought-prone environments. Post-flowering drought adaptation in sorghum is associated with the stay-green phenotype. Alleles that contribute to this complex trait have been mapped to four major QTL, Stg1-Stg4, using a population derived from BTx642 and RTx7000. Near-isogenic RTx7000 lines containing BTx642 DNA spanning one or more of the four stay-green QTL were constructed. The size and location of BTx642 DNA regions in each RTx7000 NIL were analysed using 62 DNA markers spanning the four stay-green QTL. RTx7000 NILs were identified that contained BTx642 DNA completely or partially spanning Stg1, Stg2, Stg3, or Stg4. NILs were also identified that contained sub-portions of each QTL and various combinations of the four major stay-green QTL. Physiological analysis of four RTx7000 NILs containing only Stg1, Stg2, Stg3, or Stg4 showed that BTx642 alleles in each of these loci could contribute to the stay-green phenotype. RTx7000 NILs containing BTx642 DNA corresponding to Stg2 retained more green leaf area at maturity under terminal drought conditions than RTx7000 or the other RTx7000 NILs. Under post-anthesis water deficit, a trend for delayed onset of leaf senescence compared with RTx7000 was also exhibited by the Stg2, Stg3, and Stg4 NILs, while significantly lower rates of leaf senescence in relation to RTx7000 were displayed by all of the Stg NILs to varying degrees, but particularly by the Stg2 NIL. Greener leaves at anthesis relative to RTx7000, indicated by higher SPAD values, were exhibited by the Stg1 and Stg4 NILs. The RTx7000 NILs created in this study provide the starting point for in-depth analysis of stay-green physiology, interaction among stay-green QTL and map-based cloning of the genes that underlie this trait.

Chromosome Mapping↗

PubMedDate not supplied

[Methods for transcriptome and proteome research: applications for studying the biology of reproduction in cattle].

Improvements of animal health, welfare and product quality are major goals of modern animal breeding. Thus, in addition to the classical production traits, functional traits such as disease resistance, fertility and longevity moved into the center of animal breeder's interests. Due to their low heritability, the improvement of functional traits using conventional approaches of phenotypic testing and quantitative genetics is difficult. A number of studies have been conducted worldwide in various species to map quantitative trait loci (QTLs) and to identify genetic markers for health traits. This has revealed a plethora of chromosome regions which may harbor genes with relevance for animal health. Functional genome research integrates holistic investigations at the level of the genome, at the level of gene activity (transcriptome, proteome) and at various levels of phenotypic expression. The integration of all these levels of information provides the basis for the functional dissection of complex traits. This review provides an overview of the most important strategies for holistic transcriptome and proteome analyses. The successful application of these techniques is exemplified by our studies of bovine reproductive biology.

Animals↗

PubMed2004

Robust simple sequence repeat markers for spruce (Picea spp.) from expressed sequence tags.

Traditionally, simple sequence repeat (SSR)markers have been developed from libraries of genomic DNA. However, the large, repetitive nature of conifer genomes makes development of robust, single-copy SSR markers from genomic DNA difficult. Expressed sequence tags (ESTs), or sequences of messenger RNA, offer the opportunity to exploit single, low-copy, conserved sequence motifs for SSR development. From a 20,275-unigene spruce EST set, we identified 44 candidate EST-SSR markers. Of these, 25 amplified and were polymorphic in white, Sitka, and black spruce; 20 amplified in all 3 spruce species tested; the remaining five amplified in all except one species. In addition, 101 previously described spruce SSRs (mostly developed from genomic DNA), were tested. Of these, 17 amplified across white,Sitka, and black spruce. The 25 EST-SSRs had approximately 9% less heterozygosity than the 17 genomic-derived SSRs (mean H=0.65 vs 0.72), but appeared to have less null alleles, as evidenced by much lower apparent inbreeding (mean F=0.046 vs 0.126). These robust SSRs are of particular use in comparative studies,and as the EST-SSRs are within the expressed portion of the genome, they are more likely to be associated with a particular gene of interest, improving their utility for quantitative trait loci mapping and allowing detection of selective sweeps at specific genes.

Base Sequence↗

PubMed2004

Identification of drought-inducible genes and differentially expressed sequence tags in barley.

Drought limits cereal yields in several regions of the world and plant water status plays an important role in tolerance to drought. To investigate and understand the genetic and physiological basis of drought tolerance in barley, differentially expressed sequence tags (dESTs) and candidate genes for the drought response were mapped in a population of 167 F8 recombinant inbred lines derived from a cross between "Tadmor" (drought tolerant) and "Er/Apm" (adapted only to specific dry environments). One hundred sequenced probes from two cDNA libraries previously constructed from drought-stressed barley (Hordeum vulgare L., var. Tokak) plants and 12 candidate genes were surveyed for polymorphism, and 33 loci were added to a previously published map. Composite interval mapping was used to identify quantitative trait loci (QTL) associated with drought tolerance including leaf relative water content, leaf osmotic potential, osmotic potential at full turgor, water-soluble carbohydrate concentration, osmotic adjustment, and carbon isotope discrimination. A total of 68 QTLs with a limit of detection score > or =2.5 were detected for the traits evaluated under two water treatments and the two traits calculated from both treatments. The number of QTLs identified for each trait varied from one to 12, indicating that the genome contains multiple genes affecting different traits. Two candidate genes and ten differentially expressed sequences were associated with QTLs for drought tolerance traits.

Chromosome Mapping↗

PubMed2005

A non-stationary model for functional mapping of complex traits.

SUMMARY: Understanding the genetic control of growth is fundamental to agricultural, evolutionary and biomedical genetic research. In this article, we present a statistical model for mapping quantitative trait loci (QTL) that are responsible for genetic differences in growth trajectories during ontogenetic development. This model is derived within the maximum likelihood context, implemented with the expectation-maximization algorithm. We incorporate mathematical aspects of growth processes to model the mean vector and structured antedependence models to approximate time-dependent covariance matrices for longitudinal traits. Our model has been employed to map QTL that affect body mass growth trajectories in both male and female mice of an F2 population derived from the Large and Small mouse strains. The results from this model are compared with those from the autoregressive-based functional mapping approach. Based on results from computer simulation studies, we suggest that these two models are alternative to one another and should be used simultaneously for the same dataset.

Aging↗

PubMedDate not supplied

Genes and hypertension: where we are and where we should go.

Our understanding of the genetics of hypertension is incomplete. A great deal has, however, been learned about the role of several < > genes by altering their expression in transgenic and knockout models. Crosses of inbred strains, analyzed in F2 generations, have demonstrated consistent quantitative trait loci, particularly on chromosomes 1, 2 and 10, suggesting significant contributions of some genes in distinct models of rodent hypertension. The effect of these loci has been tested in congenic strains and their interaction underlined in double congenics. The weakness of testing individual animals from F2 crosses is overcome in recombinant inbred strains. In humans, Mendelian models of hypertension have contributed to progress in our understanding of this disease, but have not yet revealed any major gene of essential hypertension. Many association as well as linkage studies of humans have provided useful though somewhat contradictory data. Our renewed effort is oriented towards the discovery of genetic determinants of environmental interaction in hypertension as well as towards the future of pharmacogenomics. This progress will be the basis of future individualized treatment and prevention.

Animals↗

PubMed2004

Polymorphisms of the porcine androgen receptor gene affecting its amino acid sequence and expression level.

Diverse physiological effects of the androgen receptor (AR), a nuclear transcription factor, and its mapping position within a quantitative trait loci (QTL) region on chromosome X propose it as an interesting candidate gene for pig reproduction and performance. Therefore, the aims of this study were isolation of the gene and detection of polymorphisms as a tool for association study and analysis of functional properties of the porcine AR. The mRNA and promoter sequences were obtained and screened for polymorphisms. Based on comparative sequencing, eight single nucleotide polymorphisms (SNPs), TG- and T-insertion/deletetion polymorphisms (INDELs) upstream transcription initiation sites, three SNPs in the 5'-untranslated region (UTR), one microsatellite (CCTTT)n in the intron of 5'-UTR, and a CAG-INDEL in exon 1 were detected. Two haplotypes originated from Duroc and Berlin Miniature Pig were segregating in the DUMI-F2 resource population. Characterization of the porcine AR promoter showed two conserved transcription start sites, a consensus sequence of GC-box and a homopurine/homopyrimidine stretch at similar locations compared to the human, rat and mouse as well as sequences similar to androgen response elements (ARE). The AR mRNA expression levels determined by real-time RT-PCR in various tissues of female pigs were high in ovary (100%) and adrenal gland (83.9% relative to ovary), moderate in uterus (61.6%) and liver (47.4%), and low in pituitary gland (1.3%) as well as in tonsil, muscle, mammary gland, leukocyte and jejunum (less than 1%). Detection of the AR mRNA transcripts in liver revealed that hemizygous males carrying the AR haplotype descended from Berlin Miniature pig had higher relative AR expressions than did those with the Duroc haplotype. Here we showed that the porcine AR is a highly polymorphic gene. Polymorphisms identified in the present study affect the predicted amino acid sequence as well as consensus transcription factor binding sites and are associated with the allele-specific differences of the AR mRNA transcript level in liver, reinforcing AR as a potential candidate gene for traits related to pig reproduction and performance.

5' Untranslated Regions↗

PubMed2006

A new method for gene discovery in large-scale microarray data.

Microarrays are an effective tool for monitoring genome-wide gene expression levels. In current microarray analyses, the majority of genes on arrays are frequently eliminated for further analysis because the changes in their expression levels (ratios) are considered to be not significant. This strategy risks failure to discover whole sets of genes related to a quantitative trait of interest, which is generally controlled by several loci that make various contributions. Here, we describe a high-throughput gene discovery method based on correspondence analysis with a new index for expression ratios [arctan (1/ratio)] and three artificial marker genes. This method allows us to quickly analyze the whole microarray dataset and discover up-/down-regulated genes related to a trait of interest. We employed an example dataset to show the theoretical advantage of this method. We then used the method to identify 88 cancer-related genes from a published microarray data from patients with breast cancer. This method also allows us to predict the phenotype of a given sample from the gene expression profile. This method can be easily performed and the result is also visible in 3D viewing software that we have developed.

Breast Neoplasms↗

PubMed1999

Identification of genes controlling collagen-induced arthritis in mice: striking homology with susceptibility loci previously identified in the rat.

The susceptibility to collagen-induced arthritis in the highly susceptible DBA/1 mouse has earlier been shown to be partly controlled by the MHC class II gene Aq. To identify susceptibility loci outside of MHC, we have made crosses between DBA/1 and the less susceptible B10.Q strain, both expressing the MHC class II gene Aq. Analysis of 224 F2 intercross mice with 170 microsatellite markers in a genome-wide scan suggested 4 quantitative trait loci controlling arthritis susceptibility located on chromosomes 6, 7, 8, and 10. The locus on chromosome 6 (Cia6), which was associated with arthritis onset, yielded a logarithm of odds score of 4.7 in the F2 intercross experiment and was reproduced in serial backcross experiments. Surprisingly, the DBA/1 allele had a recessive effect leading to a delay in arthritis onset. The suggestive loci on chromosomes 7 and 10 were associated with arthritis severity rather than onset, and another suggestive locus on chromosome 8 was most closely associated with arthritis incidence. The loci on chromosomes 7, 8, and 10 all appeared to contain disease-promoting alleles derived from the DBA/1 strain. Interestingly, most of the identified loci were situated in chromosomal regions that are homologous to regions in the rat genome containing susceptibility genes for arthritis; the mouse Cia6 locus is homologous with the rat Cia3, Pia5, Pia2, and Aia3; the locus on chromosome 7 (Cia7) is homologous with the rat Cia2; and the locus on chromosome 10 (Cia8) is homologous with the rat Cia4.

Animals↗

PubMed2005

Root response to Fusarium solani f. sp . glycines: temporal accumulation of transcripts in partially resistant and susceptible soybean.

Sudden death syndrome (SDS) of soybean is a complex of root rot disease caused by the semi-biotrophic fungus Fusarium solani f. sp. glycines (Fsg) and a leaf scorch disease caused by toxins produced by the pathogen in the roots. Development of partial rate-reducing resistance in roots to SDS was studied. The recombinant inbred line 23 (RIL23) that carried resistance conferred by six quantitative trait loci (QTL) derived from cultivars 'Essex' x 'Forrest' was compared to the susceptible cultivar Essex. Roots of RIL23 and its susceptible parent Essex were inoculated with Fsg. Transcript abundance (TA) of 191 ESTs was studied at five time points after inoculation. For most of the genes, there was an initial decrease in TA in the inoculated roots of both genotypes. By days 7 and 10 the inoculated roots of Essex failed to increase expression of the transcripts of defense-related genes. In RIL23 inoculated roots, the TA of 81 genes was increased by at least two-fold at day 3 (P=0.004), 88 genes at day 7 (P=0.0023) and 129 genes at day 10 (P=0.0026). A set of 35 genes maintained at least a two-fold higher abundance at all three time points. The increase in TA in RIL23 was in contrast to that observed in Essex where most of the ESTs showed either no change or a decreased TA. The ESTs with an increased TA had homology to the genes involved in resistance (analogs), signal transduction, plant defense, cell wall synthesis and transport of metabolites. Pathways that responded included the protein phosphorylation cascade, the phospholipase cascade and the phenolic natural products pathways, including isoflavone and cell wall synthesis.

Crosses, Genetic↗

PubMed2002

Microarray analysis of rat chromosome 2 congenic strains.

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of human essential hypertension, and a number of reproducible blood pressure regulation quantitative trait loci have been found to map to rat chromosome 2. The SP.WKYGla2c* congenic strain was produced by introgressing a region of rat chromosome 2 from the normotensive Wistar Kyoto (WKY) strain into the genetic background of the SHRSP. Systolic and diastolic blood pressures were significantly reduced in the SP.WKYGla2c* compared with the SHRSP parental strain (198/134+/-6.1/3.3 versus 172/120+/-3.8/3.4 mm Hg; F=15.8/8.1, P=0.0009/0.013). Genome-wide microarray expression profiling was undertaken to identify differentially expressed genes among the parental SHRSP, WKY, and congenic strain. We identified a significant reduction in expression of glutathione S-transferase mu-type 2, a gene involved in the defense against oxidative stress. Quantitative reverse transcription-polymerase chain reaction relative to a beta-actin standard confirmed the microarray results with SHRSP mRNA at 8.56 x 10(-4) +/-1.6 x 10(-4) compared with SP.WKYGla2c* 3.67 x 10(-3)+/-2.8 x 10(-4) (95% CI -3.9 x 10(-3) to -1.8 x 10(-3); P=0.0034) and WKY 4.03 x 10(-3)+/-5.1 x 10(-4); (95% CI -5.4 x 10(-3) to -8.9 x 10(-4); P=0.027). We also identified regions of conserved synteny, each containing the Gstm2 gene, on mouse chromosome 3 and human chromosome 1.

Animals↗

PubMed2004

Ecologically relevant stress resistance: from microarrays and quantitative trait loci to candidate genes - a research plan and preliminary results using Drosophila as a model organism and climatic and genetic stress as model stresses.

We aim at studying adaptation to genetic and environmental stress and its evolutionary implications at different levels of biological organization. Stress influences cellular processes, individual physiology, genetic variation at the population level, and the process of natural selection. To investigate these highly connected levels of stress effects, it is advisable - if not critical - to integrate approaches from ecology, evolution, physiology, molecular biology and genetics. To investigate the mechanisms of stress resistance, how resistance evolves, and what factors contribute to and constrain its evolution, we use the well-defined model systems of Drosophila species, representing both cosmopolitan species such as D. melanogaster with a known genome map, and more specialized and ecologically well described species such as the cactophilic D. buzzatii. Various climate-related stresses are used as model stresses including desiccation, starvation, cold and heat. Genetic stress or genetic load is modelled by studying the consequences of inbreeding, the accumulation of (slightly) deleterious mutations, hybridization or the loss of genetic variability. We present here a research plan and preliminary results combining various approaches: molecular techniques such as microarrays, quantitative trait loci (QTL) analyses, quantitative PCR, ELISA or Western blotting are combined with population studies of resistance to climatic and genetic stress in natural populations collected across climatic gradients as well as in selection lines maintained in the laboratory.

Adaptation, Physiological↗