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Results for “quantitative trait locus”

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PubMed2003

Genomic analysis in the sting-2 quantitative trait locus for defensive behavior in the honey bee, Apis mellifera.

We have sequenced an 81-kb genomic region from the honey bee, Apis mellifera, associated with a quantitative trait locus (QTL) sting-2 for aggressive behavior. This sequence represents the first extensive study of the honey-bee genome structure encompassing putative genes in a QTL for a behavioral trait. Expression of 13 putative genes, as well as two transcripts that were present in a honey-bee EST database, was confirmed through reverse transcription analysis of mRNA from the honey-bee head. Whereas most transcripts exhibited little or no variation between European and Africanized honey-bee alleles, one transcript demonstrated significant nonsynonymous substitutions, deletions, and insertions. All 13 putative genes lacked similarity to known invertebrate or vertebrate proteins or transcripts. This observation may be reflective of the processes that determine the genomic evolution of an insect with social behavior and/or haplo-diploidy and are an indication of the unique nature of the honey-bee genome. These results make this sequence an invaluable research tool for the ongoing honey-bee whole-genome sequencing effort.

Animals↗
PubMed1998

Test of candidate gene--quantitative trait locus association applied to fatness in mice.

We test for the contribution of five strong candidate genes for obesity to quantitative variation for fatness in mice. The candidate loci are known through their major mutant phenotypes. We propose a randomization test for overall contribution of candidate genes, based on the empirical distribution of LOD scores from a quantitative trait locus (QTL) genome scan. The test is applied to data on body fat content and male gonadal fatpad weight from a QTL genome scan with an F2 population of C57BL/6J and DBA/2J inbred mice. The test is nonsignificant in this experiment for overall body fat content. QTLs detected at an experiment-wide significance level on chromosome 4, 6, 13 and 15 have effects on mean fatness of up to 19% between the homozygotes, but map to locations where there is no strong candidate gene. The test is significant for gonadal fat pad weight in males, and gives weak support for an association with the diabetes gene.

Adipose Tissue↗
PubMed2006

The gene controlling the quantitative trait locus EPITHIOSPECIFIER MODIFIER1 alters glucosinolate hydrolysis and insect resistance in Arabidopsis.

Glucosinolates are sulfur-rich plant secondary metabolites whose breakdown products have a wide range of biological activities in plant-herbivore and plant-pathogen interactions and anticarcinogenic properties. In Arabidopsis thaliana, hydrolysis by the enzyme, myrosinase, produces bioactive nitriles, epithionitriles, or isothiocyanates depending upon the plant's genotype and the glucosinolate's structure. A major determinant of this structural specificity is the epithiospecifier locus (ESP), whose protein causes the formation of epithionitriles and nitriles. A quantitative trait locus (QTL) on chromosome 3 epistatically affects nitrile formation in combination with ESP; this QTL has been termed EPITHIOSPECIFIER MODIFIER1 (ESM1). We identified a myrosinase-associated protein as the ESM1 QTL in Arabidopsis using map-based cloning with recombinant inbred lines, natural variation transcriptomic analysis, and metabolic profiling. In planta and in vitro analyses with natural ESM1 alleles, ESM1 knockouts, and overexpression lines show that ESM1 represses nitrile formation and favors isothiocyanate production. The glucosinolate hydrolysis profile change influenced by ESM1 is associated with the ability to deter herbivory by Trichoplusia ni. This gene could provide unique approaches toward improving human nutrition.

Animals↗
PubMed2005

The non-major histocompatibility complex quantitative trait locus Cia10 contains a major arthritis gene and regulates disease severity, pannus formation, and joint damage.

OBJECTIVE: To construct rats congenic for the chromosome 2 arthritis-regulatory quantitative trait locus Cia10, originally identified in a (DA x ACI)F(2) intercross rat strain that had been assessed for collagen-induced arthritis (CIA), and to determine the effect of this congenic interval on arthritis severity, joint histologic structure, and cytokine transcription in rats with pristane-induced arthritis (PIA). METHODS: A 52.6-MB interval derived from the ACI (CIA- and PIA-resistant) strain and containing the Cia10 interval was introgressed into the DA (arthritis-susceptible) background through genotype-guided congenic breeding. Homozygous male and female DA.ACI(Cia10) congenic rats were studied for their susceptibility to and severity of PIA, and were compared with same-sex DA rats. Histologic analyses were done on hind paws collected on day 32 following the pristane injection. Levels of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) messenger RNA (mRNA) were measured with real-time polymerase chain reaction on synovial tissues from day-32 ankles. RESULTS: Both male and female DA.ACI(Cia10) congenic rats developed a significantly milder form of arthritis, with a 95% and 92% reduction in the arthritis severity index compared with DA male and female controls, respectively (males P < or = 0.001 and females P = 0.003). DA.ACI(Cia10) congenic rat synovial tissue was more likely to preserve its normal histologic architecture, including minimal to no cartilage and bone erosions, synovial hyperplasia, and pannus formation, and reduced numbers of vessels (angiogenesis), when compared with DA synovial tissue. There was a 2.7- and 2.4-fold reduction in the amount of IL-1beta and TNFalpha mRNA, respectively, in the synovial tissue of DA.ACI(Cia10) congenic rats compared with DA rats. Sequencing analyses of complementary DNA for the Cia10-predicted candidate gene Ptpn8, the rat homolog of the rheumatoid arthritis (RA)-susceptibility gene PTPN22, revealed no polymorphisms between the DA and ACI strains. CONCLUSION: This study determined that Cia10 harbors a major autoimmune arthritis-regulatory gene. This gene regulates clinical disease severity, histologic damage, and the levels of at least two central proinflammatory cytokines. We are in the process of narrowing down the critical region for positional cloning of the Cia10 gene. The identification of this gene will provide novel targets or pathways for focused candidate-gene studies in RA.

Animals↗
PubMed2002

Genetic dissection of a genomic region for a quantitative trait locus, Hd3, into two loci, Hd3a and Hd3b, controlling heading date in rice.

The rice photoperiod sensitivity gene Hd3 was originally detected as a heading date-related quantitative trait locus localized on chromosome 6 of rice. High-resolution linkage mapping of Hd3 was performed using a large segregating population derived from advanced backcross progeny between a japonica variety, Nipponbare, and an indica variety, Kasalath. To determine the genotype of Hd3, we employed progeny testing under natural field and short-day conditions. As a result, two tightly linked loci, Hd3a and Hd3b, were identified in the Hd3 region. Nearly-isogenic lines for Hd3a and Hd3b were selected from progeny using marker-assisted selection. The inheritance mode of both Hd3a and Hd3b was found to be additive. Analysis of daylength response in nearly-isogenic lines of Hd3a and Hd3b showed that the Kasalath allele at Hd3a promotes heading under short-day conditions while that at Hd3b causes late heading under long-day and natural field conditions.

Journal Article↗
PubMed2006

Sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone: a quantitative trait locus study of common genetic influence.

Previous studies have suggested that common genetic mechanisms influence sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone. We conducted two quantitative trait locus (QTL) studies to identify chromosomal regions that harbor genes that influence locomotor response to ethanol (2 g/kg) and allopregnanolone (17 mg/kg) using F2 crosses between C57BL/6J and DBA/2J mice. Because our previous data from the BXD recombinant inbred strains had indicated that chromosome 2 contained QTL for sensitivity to the locomotor-stimulant effects of both ethanol and allopregnanolone, we also tested reciprocal chromosome 2 congenic strains for sensitivity to the locomotor-stimulant effects of both drugs. The F2 analysis for ethanol sensitivity identified significant QTL on chromosomes 1 and 2 and suggestive QTL on chromosomes 5 and 9. The analysis of the allopregnanolone F2 study identified suggestive QTL on chromosomes 3, 5 and 12. Suggestive evidence for a female-specific QTL on chromosome 2 was also found. The studies of congenic mouse strains indicated that both the congenic strains captured one or more QTL for sensitivity to the locomotor-stimulant effects of both ethanol (2 g/kg) and allopregnanolone (17 mg/kg). When Fisher's method was used to combine the P values for the RI, F2 and congenic studies of the chromosome 2 QTL, cumulative probability scores of 9.6 x 10(-15) for ethanol and 7.7 x 10(-7) for allopregnanolone were obtained. These results confirm the presence of QTL for ethanol and allopregnanolone sensitivity in a common region of chromosome 2 and suggest possible pleiotropic genetic influence on sensitivity to these drugs.

Animals↗
PubMed2002

Gene expression between a congenic strain that contains a quantitative trait locus of high bone density from CAST/EiJ and its wild-type strain C57BL/6J.

Peak bone density is an important determining factor of future osteoporosis risk. We previously identified a quantitative trait locus (QTL) that contributes significantly to high bone density on mouse chromosome 1 from a cross between C57BL/6J (B6) and CAST/EiJ (CAST) mouse strains. We then generated a congenic strain, B6.CAST-1T, in which the chromosomal fragment containing this QTL had been transferred from CAST to the B6 background. The congenic mice have a significantly higher bone density than the B6 mice. In this study we performed cDNA microarray analysis to evaluate the gene expression profile that might yield insights into the mechanisms controlling the high bone density by this QTL. This study led to several interesting observations. First, approximately 60% of 8,734 gene accessions on GEM I chips were expressed in the femur of B6 mice. The expression and function of two-thirds of these expressed genes and ESTs have not been documented previously. Second, expression levels of genes related to bone formation were lower in congenic than in B6 mice. These data are consistent with a low bone formation in the congenic mice, a possibility that is confirmed by reduced skeletal alkaline phosphatase activity in serum compared with B6 mice. Third, expression levels of genes that might have negative regulatory action on bone resorption were higher in congenic than in B6 mice. Together these findings suggest that the congenic mice might have a lower bone turnover rate than B6 mice and raise the possibility that the high bone density in the congenic mice could be due to reduced bone resorption rather than increased bone formation.

Animals↗
PubMed2001

Mapping a blood pressure quantitative trait locus to a 5.7-cM region in Dahl salt-sensitive rats.

A region on rat Chromosome (Chr) 2 of the Dahl salt-sensitive rat (S) was shown previously to contain a quantitative trait locus (QTL) for blood pressure (BP). This was achieved first by linkage, followed by the use of congenic strains. A congenic strain, designated S.MNS-D2Mit6/Adh, contained a segment of Chr 2 from the Milan Normotensive (MNS) rat in the S genetic background. Since the region containing the QTL was roughly 80 cM in size, a further reduction was needed towards the positional or candidate gene cloning. Currently, two congenic substrains were made from the original strain S.MNS-D2Mit6/Adh. One of these two substrains showed a BP-lowering effect, whereas the other substrain did not. Deducing the segment not shared in the two substrains, the BP QTL has to be present in a chromosome region of roughly 5.7 cM between the marker D2Rat303 and the locus for the neutroendopeptidase gene (Nep). Nep is not included within the segment. This region does not seem to contain any candidate genes well known for the BP control. Thus, the final identification of the QTL will most likely lead to the discovery of a brand new gene for the BP regulation.

Alcohol Dehydrogenase↗
PubMed1994

Quantitative trait locus for reading disability on chromosome 6.

Interval mapping of data from two independent samples of sib pairs, at least one member of whom was reading disabled, revealed evidence for a quantitative trait locus (QTL) on chromosome 6. Results obtained from analyses of reading performance from 114 sib pairs genotyped for DNA markers localized the QTL to 6p21.3. Analyses of corresponding data from an independent sample of 50 dizygotic twin pairs provided evidence for linkage to the same region. In combination, the replicate samples yielded a chi 2 value of 16.73 (P = 0.0002). Examination of twin and kindred siblings with more extreme deficits in reading performance yielded even stronger evidence for a QTL (chi 2 = 27.35, P < 0.00001). The position of the QTL was narrowly defined with a 100:1 confidence interval to a 2-centimorgan region within the human leukocyte antigen complex.

Adolescent↗
PubMed1994

Mapping of a quantitative trait locus for blood pressure on rat chromosome 2.

A genetic map for rat chromosome 2 that includes five candidate genes for blood pressure regulation was constructed in a region containing a quantitative trait locus (QTL) for blood pressure. Two F2 populations of male rats raised on high salt (8% NaCI) diet from weaning were studied: F2(WKY x S), derived from a cross of Dahl salt-sensitive rats (S) and Wistar-Kyoto rats (WKY); and F2(MNS x S), derived from a cross of S rats and Milan normotensive strain (MNS). In both populations a blood pressure QTL was localized between Na+,K(+)-ATPase alpha 1 isoform and calmodulin-dependent protein kinase II-delta loci. The LOD score for existence of this blood pressure QTL based on the combined populations (n = 330) was 5.66 and accounted for 9.2% of the total variance and 26% of the genetic variance.

Animals↗
PubMed1998

Testing natural selection vs. genetic drift in phenotypic evolution using quantitative trait locus data.

Evolutionary biologists have long sought a way to determine whether a phenotypic difference between two taxa was caused by natural selection or random genetic drift. Here I argue that data from quantitative trait locus (QTL) analyses can be used to test the null hypothesis of neutral phenotypic evolution. I propose a sign test that compares the observed number of plus and minus alleles in the "high line" with that expected under neutrality, conditioning on the known phenotypic difference between the taxa. Rejection of the null hypothesis implies a role for directional natural selection. This test is applicable to any character in any organism in which QTL analysis can be performed.

Alleles↗
PubMed2005

Biased estimators of quantitative trait locus heritability and location in interval mapping.

In many empirical studies, it has been observed that genome scans yield biased estimates of heritability, as well as genetic effects. It is widely accepted that quantitative trait locus (QTL) mapping is a model selection procedure, and that the overestimation of genetic effects is the result of using the same data for model selection as estimation of parameters. There are two key steps in QTL modeling, each of which biases the estimation of genetic effects. First, test procedures are employed to select the regions of the genome for which there is significant evidence for the presence of QTL. Second, and most important for this demonstration, estimates of the genetic effects are reported only at the locations for which the evidence is maximal. We demonstrate that even when we know there is just one QTL present (ignoring the testing bias), and we use interval mapping to estimate its location and effect, the estimator of the effect will be biased. As evidence, we present results of simulations investigating the relative importance of the two sources of bias and the dependence of bias of heritability estimators on the true QTL heritability, sample size, and the length of the investigated part of the genome. Moreover, we present results of simulations demonstrating the skewness of the distribution of estimators of QTL locations and the resulting bias in estimation of location. We use computer simulations to investigate the dependence of this bias on the true QTL location, heritability, and the sample size.

Bias↗
PubMed2004

Further mapping and characterization of Naq1, a quantitative trait locus responsible for maternal inferior nurturing ability in RR mice.

Females of the inbred mouse RR strain have a limited ability to nurture their offspring, and frequently the young die during rearing. We previously identified a significant quantitative trait locus (QTL) responsible for the inferior nurturing ability on chromosome 5 (Naq1), on the basis of litter weight of six pups at days 7, 12, and 21 after parturition. Here, we carried out further mapping of Naq1 to define the confidence interval precisely. At the same time, we analyzed new quantitative trait variables, litter weight gain between days 7 and 12 (WG1), and that between days 12 and 21 (WG2), to characterize further the physiology of inferior nurturing ability. Consequently, a peak LOD score for the Naq1 was identified on D5Mit218 (72 cM), which was located approximately 2 cM distal to our previous expectation, as a significant QTL for WG1 (LOD 5.5), but not for WG2 (LOD 0.9). Because the growth of pups depends purely on milk obtained from the dam up to day 12 after birth, it seems possible to assume that the inferior nurturing ability in RR mice is related to defects in maternal nutritional support (that is, lactation) rather than to defects in pup growth. Naq1 is a novel QTL as far as the QTL results of relevant female reproductive traits in cattle and pigs are concerned.

Age Factors↗
PubMed2002

A quantitative trait locus that accounts for glucose intolerance maps to chromosome 8 in hereditary obese KK-A(y) mice.

KK and KK-A(y) mice serve as animal models of non-insulin-dependent diabetes mellitus with moderate obesity. Quantitative trait locus (QTL) analysis was performed to identify gene loci that account for fasting hyperglycemia, glucose intolerance and plasma insulin in 91 F(2) females of a C57BL/6JxKK-A(y) intercross. For glucose intolerance, a significant QTL was identified on chromosome 8, with a maximum lod score of 5.6. This locus had strong influence on the late phase of the intraperitoneal glucose tolerance test (IPGTT), suggesting that the locus may have role in glucose clearance rather than in mere hyperglycemia. In addition, three suggestive QTLs were identified on chromosomes 1 (fasting glucose), 3 (fasting insulin) and 4, (blood glucose at 120 min during IPGTT, and glucose intolerance).

Animals↗
PubMed2001

Possible causal relationships between cerebellar patterns of foliation and hindlimb coordination in laboratory mice: a quantitative trait locus analysis.

The cerebellum is involved in a large set of integrative functions including memory, affect, and motricity. The cerebellar patterns of foliation and their causal relationships with motricity were investigated via a wide genome scan approach and quantitative trait locus (QTL) strategy. QTLs were mapped in an F2 population derived from NZB/B1NJ and C57BL/6By inbred strains of mice for cerebellar fissures in the four vermal lobules (intraculminate, uvula, declival, and intracentral) and for hindpaw slips in a bar crossing test. No linkage was detected for uvula and intracentral fissures. We found five QTLs linked to declival fissure: Cpfd-1q and Cpfd-2q (chromosome 1), Cpfd-3q (chromosome 5), Cpfd-4q (chromosome 9), and Cpfd-5q (chromosome 13). Two QTLs were also mapped for intraculminate fissure Cpfi-1q (chromosome 4) and Cpfi-2q (chromosome 1). Most of the confidence intervals of these QTLs included genes that were previously identified for their implication in the physiological mechanisms underlying cerebellar patterns of foliation. Only one significant QTL was found for the measure of hindpaw coordination (Tne-1q). It was linked with Cpfd-1q and Cpfd-2q on the telomeric part of chromosome 1.

Animals↗
PubMed1998

Quantitative trait locus (QTL) mapping using different testers and independent population samples in maize reveals low power of QTL detection and large bias in estimates of QTL effects.

The efficiency of marker-assisted selection (MAS) depends on the power of quantitative trait locus (QTL) detection and unbiased estimation of QTL effects. Two independent samples N = 344 and 107 of F2 plants were genotyped for 89 RFLP markers. For each sample, testcross (TC) progenies of the corresponding F3 lines with two testers were evaluated in four environments. QTL for grain yield and other agronomically important traits were mapped in both samples. QTL effects were estimated from the same data as used for detection and mapping of QTL (calibration) and, based on QTL positions from calibration, from the second, independent sample (validation). For all traits and both testers we detected a total of 107 QTL with N = 344, and 39 QTL with N = 107, of which only 20 were in common. Consistency of QTL effects across testers was in agreement with corresponding genotypic correlations between the two TC series. Most QTL displayed no significant QTL x environment nor epistatic interactions. Estimates of the proportion of the phenotypic and genetic variance explained by QTL were considerably reduced when derived from the independent validation sample as opposed to estimates from the calibration sample. We conclude that, unless QTL effects are estimated from an independent sample, they can be inflated, resulting in an overly optimistic assessment of the efficiency of MAS.

Chromosome Mapping↗
PubMed2001

Aspartate kinase 2. A candidate gene of a quantitative trait locus influencing free amino acid content in maize endosperm.

The maize (Zea mays) Oh545o2 inbred accumulates an exceptionally high level of free amino acids, especially lysine (Lys), threonine (Thr), methionine, and iso-leucine. In a cross between Oh545o2 and Oh51Ao2, we identified several quantitative trait loci linked with this phenotype. One of these is on the long arm of chromosome 2 and is linked with loci encoding aspartate (Asp) kinase 2 and Asp kinase (AK)-homoserine dehydrogenase (HSDH) 2. To investigate whether these enzymes can contribute to the high levels of Asp family amino acids, we measured their specific activity and feedback inhibition properties, as well as activities of several other key enzymes involved in Lys metabolism. We did not find a significant difference in total activity of dihydrodipicolinate synthase, HSDH, and Lys ketoglutarate reductase between these inbreds, and the feedback inhibition properties of HSDH and dihyrodipicolinate synthase by Lys and/or Thr were similar. The most significant difference we found between Oh545o2 and Oh51Ao2 is feedback inhibition of AK by Lys but not Thr. AK activity in Oh545o2 is less sensitive to Lys inhibition than that in Oh51Ao2, with a Lys I50 twice that of Oh51Ao2. AK activity in Oh545o2 endosperm is also higher than in Oh51Ao2 at 15 d after pollination, but not 20 d after pollination. The results indicate that the Lys-sensitive Asp kinase 2, rather than the Thr-sensitive AK-HSDH2, is the best candidate gene for the quantitative trait locus affecting free amino acid content in Oh545o2.

Abscisic Acid↗
PubMedDate not supplied

Identification of chromosomes associated with dental caries susceptibility using quantitative trait locus analysis in mice.

Dental caries is a multifactorial, infectious disease with little known about the host genetic factors influencing susceptibility. This study aimed to identify the major candidate chromosomes for dental caries susceptibility and to detect the relevant regions within these. Quantitative trait locus (QTL) analysis was performed on genetic crosses of C3H/HeJ (caries-resistant) and C57BL/6J (caries-susceptible) mice inoculated with Streptococcus mutans serotype C. In a genomewide scan, three suggestive QTLs were detected on chromosomes 1, 2, and 7, one significant QTL was found on chromosome 2, and one highly significant QTL was detected on chromosome 8. The likelihood ratio statistic (LRS) was raised around the marker D1Mit21 in the middle region of chromosome 1, between D2Mit255 and D2Mit311 in the distal region of chromosome 2, and the region distal to D7Mit31 on chromosome 7. A significant QTL was located between the markers D2Mit237 and D2Mit101 on chromosome 2. The LRS was highly significantly raised between markers D8Mit208 and D8Mit280 on chromosome 8, and exceeded a highly significant level between markers D8Mit211 and D8Mit280. These results suggest that major gene(s) responsible for dental caries susceptibility or resistance are located in one or more of these regions.

Animals↗