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PubMed2006

Genetic dissection of the tail suspension test: a mouse model of stress vulnerability and antidepressant response.

BACKGROUND: The tail suspension test (TST) is a mouse screening test for antidepressants. METHODS: An F2 intercross was derived from NMRI and 129S6 inbred strains (n = 747). Mice underwent standardized TST with 2 sessions: (1) baseline and (2) imipramine (30 mg/kg, intraperitoneally) TST. RESULTS: A whole genome scan of this intercross mapped significant basal TST quantitative trait loci (QTL) on chromosomes (chr) 5 (peak 61 cM, Lod 5.7), 12 (peak 43 cM, Lod 5.2), and 18 (peak 51 cM, Lod 3.0). A suggestive QTL on chr 4 (peak 62 cM; Lod 3.1) overlapped regions containing previously mapped QTLs. For TST imipramine response, QTL were mapped on chr 1, 4, and 5. The chromosome 5 locus affected basal TST, antidepressant immobility response, and tail suspension-induced hyperthermia (TSIH) behaviors. An outbred NMRI F2 population provided further evidence for a chr 5 QTL. This chr 5 region harbors a cluster of gamma aminobutyric acid (GABA)-A receptor subunits and the human syntenic region includes chr 4p, 1p11, 12q24, and 22q11.24. A significant TSIH QTL (Tsih1) mapped on chr 4 near the Leptin receptor (Lepr). CONCLUSIONS: These QTL provide potential regions of interest for human genetic studies in stress-diathesis models of psychiatric illness and antidepressant responsiveness.

Animals↗
PubMed2002

Mapping of quantitative trait loci controlling broomrape (Orobanche crenata Forsk.) resistance in faba bean (Vicia faba L.).

Orobanche crenata Forsk. is a root parasite that produces devastating effects on many crop legumes and has become a limiting factor for faba bean production in the Mediterranean region. The efficacy of available control methods is minimal and breeding for broomrape resistance remains the most promising method of control. Resistance seems to be scarce and complex in nature, being a quantitative characteristic difficult to manage in breeding programmes. To identify and map the QTLs (quantitative trait loci) controlling the trait, 196 F2 plants derived from the cross between a susceptible and a resistant parent were analysed using isozymes, RAPD, seed protein genes, and microsatellites. F2-derived F3 lines were studied for broomrape resistance under field conditions. Of the 130 marker loci segregating in the F2 population, 121 could be mapped into 16 linkage groups. Simple interval mapping (SIM) and composite interval mapping (CIM) were performed using QTL Cartographer. Composite interval mapping using the maximum number of markers as cofactors was clearly the most efficient way to locate putative QTLs. Three QTLs for broomrape resistance were detected. One of the three QTLs explained more than 35% of the phenotypic variance, whereas the others accounted for 11.2 and 25.5%, respectively. This result suggests that broomrape resistance in faba bean can be considered a polygenic trait with major effects of a few single genes.

Base Sequence↗
PubMed2004

QTL analyses of drought tolerance and growth for a Salix dasyclados x Salix viminalis hybrid in contrasting water regimes.

Quantitative trait loci (QTL) for growth traits and water-use efficiency have been identified in two water regimes (normal and drought-treated) and for a treatment index. A tetraploid hybrid F2 population originating from a cross between a Salix dasyclados clone (SW901290) and a Salix viminalis clone ('Jorunn') was used in the study. The growth response of each individual including both above and below ground dry-matter production (i.e. shoot length, shoot diameter, aboveground and root dry weight, internode length, root dry weight/total dry weight, relative growth rate and leaf nitrogen content) was analysed in a replicated block experiment with two water treatments. A composite interval mapping approach was used to estimate number of QTL, the magnitude of the QTL and their position on genetic linkage maps. QTL specific for each treatment and for the treatment index were found, but QTL common across the treatments and the treatment index were also detected. Each QTL explained from 8% to 29% of the phenotypic variation, depending on trait and treatment. Clusters of QTL for different traits were mapped close to each other at several linkage groups, indicating either a common genetic base or tightly linked QTL. Common QTL identified between treatments and treatment index in the complex trait dry weight can be useful tools in the breeding and selection for drought stress tolerance in Salix.

Biomass↗
PubMed2006

Identification of simple sequence repeat (SSR) markers for acid detergent fiber in rice straw by bulked segregant analysis.

Rice straw is a significant energy source for ruminant animals. The acid detergent fiber (ADF) content of rice straw is negatively related to intake potential of forages. Therefore, improving the digestibility of rice straw by reducing ADF content is a necessary goal in breeding programs. In the present study, simple sequence repeat (SSR) markers and the bulked segregant analysis (BSA) approach were used to identify molecular markers associated with ADF. A total of 121 BC1F1 plants derived from the cross of JX974 (a cultivar with high ADF, 36.6%) and Dongxiang wild rice (a wild rice with low ADF, 31.3%), with JX974 as a recurrent parent, were used to conduct BSA. Phenotypic analysis showed that ADF displayed a normal distribution in BC1F1 population, indicating the involvement of polygenes. A SSR marker, RM566 on chromosome 9, was identified for ADF. A small linkage map consisting of five markers was constructed by adding four other markers, and a quantitative trait locus (QTL) controlling ADF was mapped at the RM321-RM566 interval, with a distance of 3.9 cM to RM566. This QTL explained 12% of the total phenotypic variation of ADF, and its additive effect was 3%. This study is the first step to map QTL for ADF, one of the plant cell wall components in rice.

Chromosome Mapping↗
PubMed1999

Targeted identification of markers linked to malaria and filarioid nematode parasite resistance genes in the mosquito Aedes aegypti.

Quantitative trait loci (QTL) have been identified for competence of the mosquito Aedes aegypti to transmit the avian malaria parasite Plasmodium gallinaceum and the human filarial parasite Brugia malayi. Efforts towards the map-based cloning of the associated genes are limited by the availability of genetic markers for fine-scale mapping of the QTL positions. Two F2 mosquito populations were subjected to bulked segregant analysis to identify random amplified polymorphic DNA (RAPD)-PCR fragments linked with the major QTL determining susceptibility to both parasites. Individual mosquitoes for the bulks were selected on the basis of their genotypes at restriction fragment length polymorphism (RFLP) loci tightly linked with the QTL. Pool-positive RAPD fragments were cloned and evaluated as RFLP markers. Of the 62 RAPD/RFLP fragments examined, 10 represented low-copy number sequences. Five of these clones were linked with the major QTL for P. gallinaceum susceptibility (pgs1), of which one clone mapped within the flanking markers that define the QTL interval. The remaining five clones were linked with the major QTL for B. malayi susceptibility (fsb1), and again one clone mapped within the flanking markers that define the QTL interval. In addition, nine RAPD/RFLP fragments were isolated that seem to be of non-mosquito origin.

Aedes↗
PubMed2005

Complex microcolinearity among wheat, rice, and barley revealed by fine mapping of the genomic region harboring a major QTL for resistance to Fusarium head blight in wheat.

A major quantitative trait locus (QTL), Qfhs.ndsu-3BS, for resistance to Fusarium head blight (FHB) in wheat has been identified and verified by several research groups. The objectives of this study were to construct a fine genetic map of this QTL region and to examine microcolinearity in the QTL region among wheat, rice, and barley. Two simple sequence repeat (SSR) markers (Xgwm533 and Xgwm493) flanking this QTL were used to screen for recombinants in a population of 3,156 plants derived from a single F(7) plant heterozygous for the Qfhs.ndsu-3BS region. A total of 382 recombinants were identified, and they were genotyped with two more SSR markers and eight sequence-tagged site (STS) markers. A fine genetic map of the Qfhs.ndsu-3BS region was constructed and spanned 6.3 cM. Based on replicated evaluations of homozygous recombinant lines for Type II FHB resistance, Qfhs.ndsu-3BS, redesignated as Fhb1, was placed into a 1.2-cM marker interval flanked by STS3B-189 and STS3B-206. Primers of STS markers were designed from wheat expressed sequence tags homologous to each of six barley genes expected to be located near this QTL region. A comparison of the wheat fine genetic map and physical maps of rice and barley revealed inversions and insertions/deletions. This suggests a complex microcolinearity among wheat, rice, and barley in this QTL region.

Fusarium↗
PubMed1999

High resolution mapping and identification of new quantitative trait loci (QTL) affecting susceptibility to Marek's disease.

Marek's disease (MD) is a lymphoproliferative disease of chickens that costs the poultry industry approximately $1 billion annually. Genetic resistance to MD is gaining increased attention to augment vaccinal control as disease outbreaks occur more frequently. Previously, analysis of a 272 F2 White Leghorn resource population measured for many MD traits and genotyped for 78 microsatellite markers revealed two and four quantitative trait loci (QTL) with significant and suggestive association, respectively, to one or more MD associated traits. Additional genetic markers have since been scored on the MD resource population to increase QTL resolution and genome coverage. Saturation of four of the QTL regions with 17 markers revealed five new QTL while 32 markers extended the genome coverage by 400 + CM and uncovered three more QTL. QTL analysis by single-point and interval mapping algorithms agreed well when marker saturation was approximately 20 CM or less. Currently 127 genetic markers cover approximately 68% of the genome that contain up to 14 MD QTL associated to one or more MD trait; seven at the significant level and seven at the suggestive level. Individually each QTL accounts for 2-10% of the variation and, in general, resistance was dominant although the resistant allele may come from either parental line. This study suggests that a limited number of genomic regions play a major role in the genetic control of MD resistance. Markers linked to these loci may be useful for selection of MD resistant stock by the poultry industry following verification of the association within their breeding populations.

Animals↗
PubMed2002

Vanaso is a candidate quantitative trait gene for Drosophila olfactory behavior.

Most animals depend on olfaction for survival and procreation. Odor-guided behavior is a quantitative trait, with phenotypic variation due to multiple segregating quantitative trait loci (QTL). Despite its profound biological importance, the genetic basis of naturally occurring variation in olfactory behavior remains unexplored. Here, we mapped a single Drosophila QTL affecting variation in avoidance response to benzaldehyde, using a population of recombinant inbred lines. Deficiency complementation mapping resolved this region into one female- and one male-specific QTL. Subsequent quantitative complementation tests to all available mutations of positional candidate genes showed that the female-specific QTL failed to complement a P-element insertional mutation, l(3)04276. The P-element insertion was in the intron of a novel gene, Vanaso, which contains a putative guanylate binding protein domain, is highly polymorphic, and is expressed in the third antennal segment, the major olfactory organ of Drosophila. No expression was detected in the fly brain, suggesting that Vanaso plays a role in peripheral chemosensory processes rather than in central integration of olfactory information. QTL mapping followed by quantitative complementation tests to deficiencies and mutations is an effective strategy for gene discovery that allows characterization of effects of recessive lethal genes on adult phenotypes and here enabled identification of a candidate gene that contributes to sex-specific quantitative variation in olfactory behavior.

Amino Acid Sequence↗
PubMed2005

Combined linkage and association mapping of quantitative trait loci by multiple markers.

Using multiple diallelic markers, variance component models are proposed for high-resolution combined linkage and association mapping of quantitative trait loci (QTL) based on nuclear families. The objective is to build a model that may fully use marker information for fine association mapping of QTL in the presence of prior linkage. The measures of linkage disequilibrium and the genetic effects are incorporated in the mean coefficients and are decomposed into orthogonal additive and dominance effects. The linkage information is modeled in variance-covariance matrices. Hence, the proposed methods model both association and linkage in a unified model. On the basis of marker information, a multipoint interval mapping method is provided to estimate the proportion of allele sharing identical by descent (IBD) and the probability of sharing two alleles IBD at a putative QTL for a sib-pair. To test the association between the trait locus and the markers, both likelihood-ratio tests and F-tests can be constructed on the basis of the proposed models. In addition, analytical formulas of noncentrality parameter approximations of the F-test statistics are provided. Type I error rates of the proposed test statistics are calculated to show their robustness. After comparing with the association between-family and association within-family (AbAw) approach by Abecasis and Fulker et al., it is found that the method proposed in this article is more powerful and advantageous based on simulation study and power calculation. By power and sample size comparison, it is shown that models that use more markers may have higher power than models that use fewer markers. The multiple-marker analysis can be more advantageous and has higher power in fine mapping QTL. As an application, the Genetic Analysis Workshop 12 German asthma data are analyzed using the proposed methods.

Alleles↗
PubMed2005

Genetic architecture of transcript-level variation in differentiating xylem of a eucalyptus hybrid.

Species diversity may have evolved by differential regulation of a similar set of genes. To analyze and compare the genetic architecture of transcript regulation in different genetic backgrounds of Eucalyptus, microarrays were used to examine variation in mRNA abundance in the differentiating xylem of a E. grandis pseudobackcross population [E. grandis x F(1) hybrid (E. grandis x E. globulus)]. Least-squares mean estimates of transcript levels were generated for 2608 genes in 91 interspecific backcross progeny. The quantitative measurements of variation in transcript abundance for specific genes were mapped as expression QTL (eQTL) in two single-tree genetic linkage maps (F(1) hybrid paternal and E. grandis maternal). EQTL were identified for 1067 genes in the two maps, of which 811 were located in the F(1) hybrid paternal map, and 451 in the E. grandis maternal map. EQTL for 195 genes mapped to both parental maps, the majority of which localized to nonhomologous linkage groups, suggesting trans-regulation by different loci in the two genetic backgrounds. For 821 genes, a single eQTL that explained up to 70% of the transcript-level variation was identified. Hotspots with colocalized eQTL were identified in both maps and typically contained genes associated with specific metabolic and regulatory pathways, suggesting coordinated genetic regulation.

Cell Differentiation↗
PubMed2004

An expanded comparative map of bovine chromosome 27 targeting dairy form QTL regions.

At present, the density of genes on the bovine maps is extremely limited and current resolution of the human-bovine comparative map is insufficient for selection of candidate genes controlling many economic traits of interest in dairy cattle. This study describes the chromosomal mapping of 10 selected gene-associated markers to bovine linkage and radiation hybrid maps to improve the breakpoint resolution in the human-bovine comparative map near two previously identified quantitative trait loci for the linear type trait, dairy form. Two regions of conserved synteny not previously described are reported between the telomeric region of bovine chromosome 27 (BTA27) and human chromosome 3 (HSA3) p24 region and between the HSA4q34.1 region and BTA8. These data increase the number of genes positioned on the bovine gene maps, refine the human-bovine comparative map, and should improve the efficiency of candidate gene selection for the dairy form trait in cattle.

Animals↗
PubMed1999

Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima fatty rat by MQM-mapping method.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously identified 11 quantitative trait loci (QTLs) responsible for NIDDM susceptibility on Chromosomes (Chrs) 1, 5, 7, 8, 9, 11, 12, 14, and 16 (Nidd1-11/of for Non-insulin-dependent diabetes 1-11/oletf) by using the interval mapping method in 160 F(2) progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. MQM-mapping, which was applied for QTL analysis based on multiple-QTL models, is reported to be more powerful than interval mapping, because in the process of mapping one QTL the genetic background, which contains the other QTLs, is controlled. Application of MQM-mapping in the F(2) intercrosses has led to a revelation of three novel QTLs on rat Chrs 5 (Nidd12/of), 7 (Nidd13/of), and 17 (Nidd14/of), in addition to Nidd1-11/of loci. The three QTLs, together with the Nidd1-11/of, account for a total of approximately 70% and approximately 85% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F(2). While the OLETF allele corresponds with increased glucose levels as expected for Nidd12 and 14/of, the Nidd13/of exhibits heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There is epistatic interaction between Nidd2 and 14/of. Additionally, our results indicated that the novel QTLs could show no linkage with body weight, but Nidd12/of has an interaction with body weight.

Animals↗
PubMed2006

Confirmation and fine mapping of ethanol sensitivity quantitative trait loci, and candidate gene testing in the LXS recombinant inbred mice.

In previous studies, we have mapped quantitative trait loci (QTLs) for hypnotic sensitivity to ethanol using a small recombinant inbred (RI) panel and a large F(2) backcross. Alcohol sensitivity is a major predictor of long-term risk for alcoholism. We remapped hypnotic sensitivity using a new set of 75 RI strains, the LXS, derived from Inbred Long Sleep and Inbred Short Sleep strains. We expected to improve mapping resolution in the QTL regions and to identify novel QTLs for loss of the righting reflex due to ethanol. We used three common mapping algorithms (R/qtl, QTL Cartographer, and WebQTL) to map QTLs in the LXS, and we compared the results. Most mapping studies use only a single algorithm, an approach that may result in failure to identify minor QTLs. We confirmed most of our previously reported QTLs, although one major QTL from earlier work (Lore2) failed to replicate, possibly because it represented multiple linked genes separated by recombination in the RI strains. We also report narrowed confidence intervals, based on mapping with a new genetic resource of more than 4000 polymorphic single-nucleotide polymorphism markers. These narrowed confidence intervals will facilitate candidate gene identification and assessment of overlap with human regions specifying risk for alcoholism. Finally, we present an approach for using these RI strains to assess evidence for candidate genes in the narrowed intervals, and we apply this method to a strong candidate, the serotonin transporter.

Alcoholism↗
PubMed2006

Investigation of two candidate genes for meat quality traits in a quantitative trait locus region on SSC6: the porcine short heterodimer partner and heart fatty acid binding protein genes.

A highly significant quantitative trait locus (QTL) on pig chromosome 6, affecting intramuscular fat (IMF), has previously been detected by our group and others. Two genes of positional and biological interest, the small heterodimer partner (SHP; NR0B2) and the heart fatty acid binding protein (FABP3; H-FABP), were investigated for meat quality traits and IMF respectively. SHP was partially sequenced (GenBank: DQ002896 and DQ002897) and mapped to the QTL region on porcine chromosome 6, affecting IMF. The map shows no recombination between SHP and FABP3, which was previously mapped to the same QTL region. Twelve single nucleotide polymorphisms were detected in the sequenced region of SHP gene. Haplotype information was used to investigate association between genetic variation and different meat quality traits. SHP haplotype combinations were found to have significant effect on connective tissue. However, further studies are needed to evaluate this possible association more effectively. The FABP3 is involved in fatty acid transport and has been studied as a candidate gene for IMF by several research groups. In our study, FABP3 genotypes were confirmed to be significantly associated with IMF in pigs. The average content of IMF in our population was 1.6%, which may indicate that the FABP3 polymorphism explains as much as 30-35% of the variation in IMF in our pig cross-population.

Animals↗
PubMed2004

The effect of an imprecise map on interval mapping QTLs.

The statistical analysis of quantitative trait locus (QTL) experiments relies on the use of a linkage map of the markers genotyped. Such a map is, at best, a good estimate of the true map. Resources might be diverted into developing better marker maps or improved maps become available after the analysis, raising concerns over the original analysis. It is therefore important to understand the sensitivity of QTL analysis to map inaccuracy. We have used simulation methods to investigate the consequences of an incorrect map on the results of a QTL analysis using interval mapping. Backcross data sets were generated with a particular map and then analysed with both the correct map and incorrect maps. If the incorrect maps maintained the true linkage groups (i.e. no markers were incorrectly assigned to another linkage group), the accuracy of the map had little or no impact on the ability to detect QTLs, the true significance levels of the tests or the relative placement of QTLs. When a marker was incorrectly placed on another linkage group, there was a small increase in the level of the test. After adjusting for this increase, there was a decrease in power to detect a QTL near the misplaced marker. This decrease was of a similar magnitude to that found when using a single-marker analysis compared with interval mapping. These results mean that QTL analyses can proceed without the need for very accurate marker maps, and that estimated QTL positions can be translated onto updated maps without the need for reanalysis.

Chromosome Mapping↗
PubMed2000

A primary screen of the bovine genome for quantitative trait loci affecting twinning rate.

An autosomal genome scan for quantitative trait loci (QTL) affecting twinning rate was carried out in the Norwegian Cattle population. Suggestive QTL were detected on Chromosomes (Chr) 5, 7, 12, and 23. Among these, the QTL positions on both Chr 5 and Chr 23 are strongly supported by literature in the field. Our results also confirm previous mapping of a QTL for twinning to Chr 7, but definitely suggest a different location of the QTL on this chromosome. The most convincing QTL peak was observed for a region in the middle part of Chr 5 close to the insulin-like growth factor 1 (IGF1) gene. Since IGF1 plays an important role in the regulation of folliculogenesis, a mutation search was performed by sequencing more than 3.5 kb of the gene in actual families. The sequencing revealed three polymorphisms in noncoding regions of the gene that will be important in fine structure mapping and characterization of the QTL.

Animals↗
PubMed2003

Comparative analyses of genomic locations and race specificities of loci for quantitative resistance to Pyricularia grisea in rice and barley.

Comparative genomic analyses have revealed extensive colinearity in gene orders in distantly related taxa in mammals and grasses, which opened new horizons for evolutionary study. The objective of our study was to assess syntenic relationships of quantitative trait loci (QTL) for disease resistance in cereals by using a model system in which rice and barley were used as the hosts and the blast fungus Pyricularia grisea Sacc. as the pathogen. In total, 12 QTL against three isolates were identified in rice; two had effects on all three isolates, and the other 10 had effects on only one or two of the three isolates. Twelve QTL for blast resistance were identified in barley; one had effect on all three isolates, and the other 11 had effects on only one or two of the three isolates. The observed isolate specificity led to a hypothesis about the durability of quantitative resistance commonly observed in many plant host-pathogen systems. Four pairs of the QTL showed corresponding map positions between rice and barley, two of the four QTL pairs had complete conserved isolate specificity, and another two QTL pairs had partial conserved isolate specificity. Such corresponding locations and conserved specificity suggested a common origin and conserved functionality of the genes underlying the QTL for quantitative resistance and may have utility in gene discovery, understanding the function of the genomes, and identifying the evolutionary forces that structured the organization of the grass genomes.

Hordeum↗