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Results for “Expression quantitative trait locus analysis”

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PubMed2003

Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila.

We employed quantitative trait locus (QTL) mapping to dissect the genetic architecture of a hierarchy of functionally related physiological traits, including metabolic enzyme activity, metabolite storage, metabolic rate, and free-flight performance in recombinant inbred lines of Drosophila melanogaster. We identified QTL underlying variation in glycogen synthase, hexokinase, phosphoglucomutase, and trehalase activity. In each case variation mapped away from the enzyme-encoding loci, indicating that trans-acting regions of the genome are important sources of variation within the metabolic network. Individual QTL associated with variation in metabolic rate and flight performance explained between 9 and 35% of the phenotypic variance. Bayesian QTL analysis identified epistatic effects underlying variation in flight velocity, metabolic rate, glycogen content, and several metabolic enzyme activities. A region on the third chromosome was associated with expression of the glucose-6-phosphate branchpoint enzymes and with metabolic rate and flight performance. These genomic regions are of special interest as they may coordinately regulate components of energy metabolism with effects on whole-organism physiological performance. The complex biochemical network is encoded by an equally complex network of interacting genetic elements with potentially pleiotropic effects. This has important consequences for the evolution of performance traits that depend upon these metabolic networks.

Animals↗
PubMed2005

Genetic characterisation of dough rheological properties in a wheat doubled haploid population: additive genetic effects and epistatic interactions.

Doubled haploid lines (n = 160) from a cross between wheat cultivars 'Cranbrook' (high dough extensibility) and 'Halberd' (low dough extensibility) were grown at three Australian locations. The parents differ at all high- and low-molecular-weight glutenin loci. Dough rheological parameters were measured using small-scale testing procedures, and quantitative trait locus (QTL) mapping procedures were carried out using an existing well-saturated genetic linkage map for this cross. Genetic parameters were estimated using three software packages: QTLCartographer, Epistat and Genstat. Results indicated that environmental factors are a major determinant of dough extensibility across the three trial sites, whereas genotypic factors are the major determinants of dough strength. Composite interval mapping analysis across the 21 linkage groups revealed that as expected, the main additive QTLs for dough rheological properties are located at the high- and low-molecular-weight glutenin loci. A new QTL on chromosome 5A for M-extensibility (a mixograph-estimated measure of extensibility) was detected. Analysis of epistatic interactions revealed that there were significant conditional epistatic interactions related with the additive effects of glutenin loci on dough rheological properties. Therefore, the additive genetic effects of glutenins on dough rheological properties are conditional upon the genetic background of the wheat line. The molecular basis of the interactions with the glutenin loci may be via proteins that modify or alter the gluten protein matrix or variations in the expression level of the glutenin genes. Reverse-phase high performance liquid chromatography analysis of the molar number of individual glutenin subunits across the population showed that certain conditional epistases resulted in increased expression of the affected glutenin. The epistatic interactions detected in this study provide a possible explanation of the variable genetic effects of some glutenins on quality attributes in different genetic backgrounds and provide essential information for the accurate prediction of glutenin related variance in marker-assisted wheat breeding.

Alleles↗
PubMedDate not supplied

The Wilhelmine E. Key 1987 invitational lecture. Genetic changes associated with the evolution of adaptedness in cultivated plants and their wild progenitors.

The results of long-term studies of changes in adaptedness in a number of experimental populations of annual plants are summarized. Measurements made of quantitative traits showed that cumulative increases in reproductive capacity continued in these experimental populations for more than 50 generations. Highly significant allelic frequency changes also occurred for marker loci governing morphological variants, disease resistance, allozymes, and rDNA restriction fragments. Individual effects of the marker loci on quantitative traits were determined by extensive progeny testing of selfed families descended from single plants isolated from various generations of the experimental populations. Comparisons between homozygotes and heterozygotes of marker loci for quantitative trait expression revealed that all the marker loci studied had statistically significant additive effects on several to many quantitative traits; thus, each Mendelian locus, in addition to being a locus for its discrete descriptive effect, was also a locus for several quantitative traits. Consistent associations were found between superior reproductive capacity (e.g., larger numbers of kernels per plant) and the alleles of marker loci that increased in frequency over generations; no other quantitative traits measured were clearly and consistently associated with alleles that increased in frequency. Multilocus analyses based on canonical correlation, log linear, and cluster analysis procedures showed that highly significant associations developed in early generations among alleles of different loci in all the predominantly selfing populations studied. Dynamic changes featuring amalgamations of alleles into fewer clusters involving larger numbers of loci continued into the late generations. Patterns of ecogenetic differentiation that developed under predominant selfing were found to be fine-scaled overlays of environmental heterogeneity. The picture of evolutionary change that emerges is one in which the incorporation of increasing numbers of favorably interacting alleles into large synergistic complexes was accompanied in inbreeding populations by increases in adaptedness to the local environment and also by striking ecogenetic differentiation among local populations that occupy unlike habitats, including differentiation between cultivated plants and their wild progenitors. Selfing appears to promote the development and maintenance of adaptedness within populations and at the same time to facilitate the development of spatial differentiation by retarding gene flow between populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMedDate not supplied

Mu opioid receptor gene variants: lack of association with alcohol dependence.

The mu opioid receptor is implicated in the reward, tolerance and withdrawal effects of alcohol and other drugs of abuse. This hypothesis is supported by the effects of alcohol on beta-endorphin release, of mu opioid receptor agonists and antagonists on alcohol consumption, and by the activation of the dopaminergic reward system by both alcohol and opiates. In addition, the murine mu opioid receptor locus, Oprm, is implicated as the major quantitative trait locus (QTL) affecting the different levels of morphine consumption between two inbred mouse strains that also exhibit differences in alcohol and cocaine consumption. Detection of genetic variation affecting OPRM1 expression or mu opioid receptor function would be an important step towards understanding the origins of inter-individual variation in response to mu opioid receptor ligands and in diseases of substance dependence. We directly sequenced the human mu opioid receptor locus, OPRM1, to detect natural variation that might affect function and/or be associated with psychiatric phenotypes related to opioid function. Four DNA sequence variants were found: three non-synonymous substitutions (Ala6Val [rare], Asn40Asp, [0.10-0.16], Ser147Cys [rare]) and one intronic variant (IVS2+691G/C [0.55-0.63]). OPRM1 alleles, genotypes and haplotypes from three psychiatrically characterized population samples (US Caucasian [USC, n=100], Finnish Caucasian [FC, n=324] and Southwestern American Indian [SAI, n=367]), were used to perform association and sib-pair linkage analyses with alcohol and drug dependence diagnoses. No significant association of OPRM1 genetic variation to phenotype was observed. This analysis has 80% power to detect a small to moderate effect of OPRM1 variation on alcohol dependence and 100% power to detect effects of the magnitude of the ALDH2*2 variant. While these data do not support a role of the mu opioid receptor in susceptibility to alcohol dependence, the potential relationship between OPRM1 genetic variation and response to endogenous opioids and exogenous opiates can now be investigated.

Adult↗
PubMed1999

Genetic linkage of hyper-IgE syndrome to chromosome 4.

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as an autosomal dominant trait with variable expressivity. Nineteen kindreds with multiple cases of HIES were scored for clinical and laboratory findings and were genotyped with polymorphic markers in a candidate region on human chromosome 4. Linkage analysis showed a maximum two-point LOD score of 3.61 at recombination fraction of 0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES.

Chromosome Deletion↗
PubMed2000

An integrated map of human 6q22.3-q24 including a 3-Mb high-resolution BAC/PAC contig encompassing a QTL for fetal hemoglobin.

Genetic studies have previously assigned a quantitative trait locus (QTL) for hemoglobin F and F cells to a region of approximately 4 Mb between the markers D6S408 and D6S292 on chromosome 6q23. An initial yeast artificial chromosome contig of 13 clones spanning this region was generated. Further linkage analysis of an extended kindred refined the candidate interval to 1-2 cM, and key recombination events now place the QTL within a region of <800 kb. We describe a high-resolution bacterial clone contig spanning 3 Mb covering this critical region. The map consists of 223 bacterial artificial chromosome (BAC) and 100 P1 artificial chromosome (PAC) clones ordered by sequence-tagged site (STS) content and restriction fragment fingerprinting with a minimum tiling path of 22 BACs and 1 PAC. A total of 194 STSs map to this interval of 3 Mb, giving an average marker resolution of approximately one per 15 kb. About half of the markers were novel and were isolated in the present study, including three CA repeats and 13 single nucleotide polymorphisms. Altogether 24 expressed sequence tags, 6 of which are unique genes, have been mapped to the contig.

Base Sequence↗
PubMed2003

Molecular mapping of capsaicinoid biosynthesis genes and quantitative trait loci analysis for capsaicinoid content in Capsicum.

Quantitative variation in the accumulation of two major capsaicinoids responsible for pungency in the fruit of chile peppers, capsaicin and dihydrocapsaicin, was analyzed in a cross between the non-pungent Capsicum annuum parent cv. Maor and a pungent Capsicum frutescens parent, accession BG 2816. In order to identify quantitative trait loci (QTLs) for capsaicinoid content, we employed the bulked segregant analysis method and screened bulked DNA from F2 individuals at the extremes of the distribution of capsaicinoid content with RAPD primers. Screening with 400 primers allowed the identification of three loci that were polymorphic between the bulks. These RAPD markers were converted to SCARs and subsequently mapped with additional RFLP markers to chromosome 7 of pepper. QTL interval analysis for individual and total capsaicinoid content identified a major QTL, termed cap, which explained 34-38% of the phenotypic variation for this trait in two growing environments. For all measurements, the allele of the pungent parent BG 2816 at cap contributed to the increased level of pungency. To determine whether known structural genes in the pathway could define a candidate for this QTL, 12 clones obtained from differentially expressed transcripts from placental tissue in pungent peppers were also mapped. None of them had a significant effect on this trait, nor did the allelic state at the locus C, the on/off switch for pungency in pepper, located on chromosome 2. The identity of cap and its effect on capsaicin content in other backgrounds will be addressed in future studies.

Alleles↗
PubMed2001

Two tightly linked QTLs modify tomato sugar content via different physiological pathways.

Congenic lines that differ in a single defined chromosome segment are useful for the study of complex phenotypes, as they allow isolation of the effect of a particular quantitative trait locus (QTL) from those of the entire genome. We conducted high-resolution QTL mapping of a 9-cM introgression, originating from the wild tomato species Lycopersicon pennellii, in two extremely different genetic and physiological backgrounds. In the "indeterminate" glasshouse background we identified only a single QTL ( Brix9-2-5) that affects the total soluble solids of the fruit [mainly sugars, measured in Brix units (B)]. This QTL was previously delimited within the gene for an apoplastic invertase, Lin5, that modulates sugar partitioning to the fruit. Analysis of the effects of the same chromosome segment in "determinate", open-field tomatoes, revealed two QTLs, 0.3 cM apart: the fruit-specific Brix9-2-5 that affects B only, and the shoot-specific PW9-2-5, which accounts for an altered growth habit resulting in increases in plant weight, yield, and B. This study highlights the power of the congenic approach for dissecting developmental pathways leading to complex phenotypes.

Base Sequence↗
PubMed2006

Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22.

Pre-eclampsia/eclampsia (PE/E) is a common, serious medical disorder of human pregnancy. Familial association of PE/E has been recognized for decades, but the genetics are complex and poorly understood. In an attempt to identify PE/E susceptibility genes, we embarked on a positional cloning strategy using 34 Australian and New Zealand PE/E pedigrees. An initial 10-cM resolution genome scan revealed a putative susceptibility locus spanning a broad region on chromosome 2 that overlaps an independently determined linkage signal seen in Icelandic PE pedigrees. Subsequent fine mapping using 25 additional short tandem repeat (STR) markers in this region and non-parametric multipoint linkage analysis did not change the overall position. Under a strict diagnosis of PE, we obtained significant evidence of linkage on 2q with a peak log-of-odds ratio score (LOD) of 3.43 near marker D2S151 at 155 cM. To prioritize positional candidate genes at the 2q locus for detailed analysis, we applied an objective prioritization strategy that integrates quantitative bioinformatics, assessment of differential gene expression and association analysis of single-nucleotide polymorphisms (SNPs). Highest priority was assigned to the activin receptor gene ACVR2. This gene also showed >10-fold differential gene expression in human decidual tissue from normotensive and PE individuals. We genotyped five known SNPs in this gene in our pedigrees and performed tests for association and linkage disequilibrium. One SNP (rs1424954) showed strong preliminary evidence of association with PE (P = 0.007), whereas two others (rs1364658 and rs1895694) exhibited nominal evidence (P < 0.05). Haplotype analysis revealed no additional association information. There was evidence of weak linkage disequilibrium among these SNPs. The highest observed LD occurred between the two strongest associated SNPs, suggesting that the observed signals may be the signature of an observed functional variant.

Activin Receptors, Type II↗
PubMed2004

Mammalian circadian biology: elucidating genome-wide levels of temporal organization.

During the past decade, the molecular mechanisms underlying the mammalian circadian clock have been defined. A core set of circadian clock genes common to most cells throughout the body code for proteins that feed back to regulate not only their own expression, but also that of clock output genes and pathways throughout the genome. The circadian system represents a complex multioscillatory temporal network in which an ensemble of coupled neurons comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is entrained to the daily light/dark cycle and subsequently transmits synchronizing signals to local circadian oscillators in peripheral tissues. Only recently has the importance of this system to the regulation of such fundamental biological processes as the cell cycle and metabolism become apparent. A convergence of data from microarray studies, quantitative trait locus analysis, and mutagenesis screens demonstrates the pervasiveness of circadian regulation in biological systems. The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.

Animals↗
PubMed2026

Mapping the causal chain from genetic risk variants to lipid dysmetabolism in Parkinson's disease.

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analysed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain to reveal pertinent mechanisms. We show that common PD risk variants at the serine palmitoyltransferase small subunit B (SPTSSB) locus, a key regulator of de novo sphingolipid biosynthesis, are associated with increased SPTSSB brain expression and elevated plasma ceramides. Additional analyses strongly support our hypothesis that a common SPTSSB causal variant is responsible for PD risk as well as the expression and metabolic quantitative trait loci. Multiple sphingolipids and fatty acid derivatives were perturbed in PD, and we identified both unique and shared features with the Alzheimer's disease metabolome. A PD acylcarnitine signature was further replicated in human post-mortem brain tissue, when comparing those with or without preclinical Lewy body pathology. Integrated analysis of complementary brain proteomic profiles revealed dysregulation of mitochondrial processes dependent on acylcarnitines, including fatty acid beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation. Our results identify promising biomarkers and reveal a causal chain linking genetic variation to altered gene/protein expression, lipid dysmetabolism, and the manifestation of PD.

Humans↗
PubMed1998

Independent genetic susceptibility to cardiac hypertrophy in inherited hypertension.

Cardiac hypertrophy is a common but not inevitable complication of hypertension. Variation in heart size in hypertensives may reflect independent genetic susceptibility to cardiac hypertrophy. Using an experimental genetic model, we determined the location of quantitative trait loci responsible for cardiac hypertrophy and/or hypertension. We studied 182 F2 male animals derived from a cross of the spontaneously hypertensive rat and normotensive Donryu rats. Direct mean arterial pressure (MAP) and left ventricular (LV) mass were measured at 20 weeks of age, and DNA was obtained for linkage analysis. The estimated heritability of MAP was 62% and for LV mass expressed per unit of body weight (relative LV mass) was 76%. We used 185 polymorphic markers, with an average intermarker distance of 12.3 centimorgans for a genome-wide scan in a representative subgroup of 46 animals to identify preliminary quantitative trait loci, which were then mapped in all 182 male F2 rats. Two loci showed logarithm of the odds scores of > 4.0. One on chromosome 2, Lvm-1, was linked to relative LV mass but showed no evidence of linkage to MAP. Another locus on chromosome 1, Map-1, was linked to MAP. In the same region, a locus Lvm-2 was linked with relative LV mass. These data indicate the existence of a genetic locus on chromosome 2 of the spontaneously hypertensive rat that affects relative LV mass independently of blood pressure.

Animals↗
PubMed1999

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

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

Animals↗
PubMed2006

PlantQTL-GE: a database system for identifying candidate genes in rice and Arabidopsis by gene expression and QTL information.

We have designed and implemented a web-based database system, called PlantQTL-GE, to facilitate quantitatine traits locus (QTL) based candidate gene identification and gene function analysis. We collected a large number of genes, gene expression information in microarray data and expressed sequence tags (ESTs) and genetic markers from multiple sources of Oryza sativa and Arabidopsis thaliana. The system integrates these diverse data sources and has a uniform web interface for easy access. It supports QTL queries specifying QTL marker intervals or genomic loci, and displays, on rice or Arabidopsis genome, known genes, microarray data, ESTs and candidate genes and similar putative genes in the other plant. Candidate genes in QTL intervals are further annotated based on matching ESTs, microarray gene expression data and cis-elements in regulatory sequences. The system is freely available at http://www.scbit.org/qtl2gene/new/.

Arabidopsis↗
PubMed2000

A recombination hotspot delimits a wild-species quantitative trait locus for tomato sugar content to 484 bp within an invertase gene.

In nature, genetic variation usually takes the form of a continuous phenotypic range rather than discrete classes. The genetic variation underlying quantitative traits results from the segregation of numerous interacting quantitative trait loci (QTLs), whose expression is modified by the environment. To uncover the molecular basis of this variation, we characterized a QTL (Brix9-2-5) derived from the green-fruited tomato species Lycopersicon pennellii. The wild-species allele increased glucose and fructose contents in cultivated tomato fruits in various genetic backgrounds and environments. Using nearly isogenic lines for the QTL, high-resolution mapping analysis delimited Brix9-2-5 to a single nucleotide polymorphism-defined recombination hotspot of 484 bp spanning an exon and intron of a fruit-specific apoplastic invertase. We suggest that the differences between the Brix9-2-5 alleles of the two species are associated with a polymorphic intronic element that modulates sink strength of tomato fruits. Our results demonstrate a link between naturally occurring DNA variation and a Mendelian determinant of a complex phenotype for a yield-associated trait.

Alleles↗
PubMed2005

Insulin-like growth factor 2 as a candidate gene influencing growth and carcass traits and its bialleleic expression in chicken.

We have identified DNA polymorphisms in the gene of insulin-like growth factor 2 by PCR-SSCP in a resource population, which was generated by Silky reciprocally crossing to Broilers. A C --> G mutation was detected in the exon 2 (at position 71) by sequencing. This single nucleotide polymorphism (SNP) was found to be associated with production traits. Chicken with BB genotype showed more chest angle width but less 3 week body weight and glandular stomach weight than chicken with AA genotype (P < 0.05); while the heterozygote (AB genotype) chicken had more abdominal fat weight, eviscerated yield with giblet than AA homozygote chicken. Further analysis showed that there were different genetic effects on some traits between heterozygote AB (paternal allele given first) and heterozygote BA: chickens with genotype BA had more birth weight and breast weight but less abdominal fat weight than chickens with genotype AB (P < 0.05), which could be hypothetically contributed by genome imprinting. Therefore, Silky chickens were selected for production of heterozygotes to confirm whether IGF2 locus was imprinting. Progeny from heterozygote x homozygote reciprocal cross was assayed for expression after the genotype was determined. The transcription of IGF2 was detected by RT-PCR-SSCP. IGF2 gene was expressed bialleleically in 1-day-old neonatal liver and 90-day-old liver, kidney, heart, and muscle of both heterozygote AB and BA chickens. Therefore, IGF2 was not an imprinting gene in chicken. The different genetic effects between the heterozygote AB and BA remain to be elucidated.

Alleles↗
PubMed1995

Cold-Specific Induction of a Dehydrin Gene Family Member in Barley.

An interval on barley (Hordeum vulgare L.) chromosome 7 accounting for significant quantitative trait locus effects for winter hardiness were detected in a winter (Dicktoo) x spring (Morex) barley population (P.M. Hayes, T. Blake, T.H.H. Chen, S. Tragoonrung, F. Chen, A. Pan, and B. Liu [1993] Genome 36: 66-71). Two members of the barley dehydrin gene family, Dhn1 and Dhn2, were located within the region defining the winter hardiness quantitative trait locus effect (A. Pan, P.M. Hayes, F. Chen, T. Blake, T.H.H. Chen, T.T.S. Wright, I. Karsai, Z. Bedo [1994] Theor Appl Genet 89: 900-910). To investigate the possible role of Dhn1 and Dhn2 in winter hardiness, we examined the expression pattern of six barley dehydrin gene family members in shoot tissue in response to cold temperature. Incubation of 3-week-old barley plants at 2[deg]C resulted in a rapid induction of a single 86-kD polypeptide that was recognized by an antiserum against a peptide conserved in the dehydrin gene family. Northern blot analysis confirmed the induction of an mRNA corresponding to Dhn5. The expression patterns of cold-induced dehydrins in shoot tissue for Dicktoo and Morex were identical under the conditions studied, in spite of the known phenotypic differences in their winter hardiness. These results, together with the allelic structure of selected high- and low-survival lines, suggest that the Dicktoo alleles at the Dhn1 and Dhn2 may not be the primary determinants of winter hardiness in barley.

Journal Article↗
PubMed2006

Combined expression trait correlations and expression quantitative trait locus mapping.

Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. The consideration of gene expression correlation over a time or tissue dimension has proved valuable in predicting gene function. Here, we consider correlations over a genetic dimension. In addition to identifying coregulated genes, the genetic dimension also supplies us with information about the genomic locations of putative regulatory loci. We calculated correlations among approximately 45,000 expression traits derived from 60 individuals in an F2 sample segregating for obesity and diabetes. By combining the correlation results with linkage mapping information, we were able to identify regulatory networks, make functional predictions for uncharacterized genes, and characterize novel members of known pathways. We found evidence of coordinate regulation of 174 G protein-coupled receptor protein signaling pathway expression traits. Of the 174 traits, 50 had their major LOD peak within 10 cM of a locus on Chromosome 2, and 81 others had a secondary peak in this region. We also characterized a Riken cDNA clone that showed strong correlation with stearoyl-CoA desaturase 1 expression. Experimental validation confirmed that this clone is involved in the regulation of lipid metabolism. We conclude that trait correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we studied only mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping alone.

Animals↗