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MeSH Review:

Quantitative Trait Loci

Wittenburg, H. et al., Palmer, A.A. et al., Karp, C.L. et al., Bassett, S.S. et al., Liston, A. et al., et al.

Phelan, Wang, Wallbrandt, Forsman-Semb, Paigen, Mogil, Wilson, Chesler, Rankin, Nemmani, Lariviere, Groce, Wallace, Kaplan, Staud, Ness, Glover, Stankova, Mayorov, Hruby, Grisel, Fillingim, Welch, Bretschger, Latib, Bezouevski, Guo, Pleskac, Liang, Barlow, Dansky, Breslow, Tall, Karp, Grupe, Schadt, Ewart, Keane-Moore, Cuomo, Köhl, Wahl, Kuperman, Germer, Aud, Peltz, Wills-Karp, Aitman, Gotoda, Evans, Imrie, Heath, Trembling, Truman, Wallace, Rahman, Doré, Flint, Kren, Zidek, Kurtz, Pravenec, Scott, Bassett, Kusevic, Cristinzio, Yassa, Avramopoulos, Yousem, Fallin, Austin, Edwards, Monks, Koprowicz, Brunzell, Motulsky, Mahaney, Hixson, Markel, Fulker, Bennett, Corley, DeFries, Erwin, Johnson, Wang, Ria, Kelmenson, Eriksson, Higgins, Samnegård, Petros, Rollins, Bennet, Wiman, de Faire, Wennberg, Olsson, Ishii, Sugamura, Hamsten, Forsman-Semb, Lagercrantz, Paigen, Vincent, Samani, Gauguier, Thompson, Lathrop, Sassard, Alonso-Blanco, Gomez-Mena, Llorente, Koornneef, Salinas, Martínez-Zapater, Olsson, Piehl, Swanberg, Lidman,

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Disease relevance of Quantitative Trait Loci

Here we refine a quantitative trait locus that confers susceptibility to hepatic fibrosis by in silico mapping and show, using congenic mice and transgenesis with recombined artificial chromosomes, that the gene Hc (encoding complement factor C5) underlies this locus [1].
Here we report the positional cloning of an auditory quantitative trait locus (QTL), the modifier of tubby hearing 1 gene (moth1), whose wildtype alleles from strains AKR/J, CAST/Ei and 129P2/OlaHsd protect tubby mice from hearing loss [2].
No associations were observed between the quantitative trait loci and levels of plasma total cholesterol, high density lipoprotein cholesterol, non-high density lipoprotein cholesterol, insulin, or body weight [3].
This study identified cytokine deficiency-induced colitis susceptibility (Cdcs) modifiers by using quantitative trait locus (QTL) analysis [4].
A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs [5].

Psychiatry related information on Quantitative Trait Loci

BACKGROUND: In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior [6].
Our results suggest that domains common to SSD and dyslexia are pleiotropically influenced by a putative quantitative trait locus on chromosome 3 [7].
Previously, we reported evidence of genetic heterogeneity in late-onset familial Alzheimer's disease, based on sex of affected parent, demonstrating linkage to chromosome 10q, a region identified by other groups and implicated as a quantitative trait loci for Abeta levels, in families with an affected mother [8].
In an effort to identify genes that may be important for drug-abuse liability, we mapped behavioral quantitative trait loci (bQTL) for sensitivity to the locomotor stimulant effect of methamphetamine (MA) using two mouse lines that were selectively bred for high MA-induced activity (HMACT) or low MA-induced activity (LMACT) [9].
We are mapping the genes (quantitative trait loci or QTLs) that are responsible for individual differences in ethanol sensitivity, measured as the duration of loss of righting, reflex (LORR) and blood ethanol concentrations upon recovery of the righting reflex (BEC) [10].

High impact information on Quantitative Trait Loci

Ath1 is a quantitative trait locus on mouse chromosome 1 that renders C57BL/6 mice susceptible and C3H/He mice resistant to diet-induced atherosclerosis [11].
The quantitative trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40l or Cd134l), which encodes OX40 ligand [11].
We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety [12].
All attempts to map quantitative-trait loci (QTLs) influencing dyslexia susceptibility have targeted specific chromosomal regions, so that inferences regarding genetic etiology have been made on the basis of very limited information [13].
The association of Pla2g2a with Mom1 thus withstands a strong functional test and is likely to represent the successful identification of a polymorphic quantitative trait locus in mammals [14].

Chemical compound and disease context of Quantitative Trait Loci

Genetic mapping was used to determine whether the quantitative trait loci (QTL), which influence susceptibility to bleomycin-induced lung fibrosis in these progenitor strains, could be implicated in susceptibility to radiation-induced lung fibrosis [15].
A genome-wide screen for loci linked to glucose homeostasis and body weight allowed us to map three quantitative trait loci (QTLs) involved in this disorder [16].
Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia [17].
Edpm5 is one member of a group of quantitative trait loci that are responsible for the difference in susceptibility to estrogen-induced prolactinoma between the Fischer 344 (F344) and Brown Norway (BN) strains [18].

Biological context of Quantitative Trait Loci

Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension [19].
Using microarray analysis of pulmonary gene expression and single nucleotide polymorphism-based genotyping, combined with quantitative trait locus analysis, we identified the gene encoding complement factor 5 (C5) as a susceptibility locus for allergen-induced airway hyperresponsiveness in a murine model of asthma [20].
The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity [21].
Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes [22].
Using microsatellite markers, a quantitative trait locus was identified and mapped on rat chromosome 2 that specifically influences the systolic (peak LOD score 4.4) and diastolic (peak LOD score 4.1) blood pressure responses to administration of a dihydropyridine calcium antagonist, PY108-068 [23].

Anatomical context of Quantitative Trait Loci

The number of bone marrow hematopoietic stem and progenitor cells as defined by the lineage(-), Sca1(++), c-kit(+) (LSK) phenotype and their proliferative capacity in vitro are subject to quantitative genetic variation, and several quantitative trait loci (QTL) have been identified in young mice [24].
To evaluate the presence of other hepatocarcinogenesis-related loci in the BFF1 genome, nodule induction by resistant hepatocyte model in 116 male BFF2 rats 32 weeks after initiation with diethylnitrosamine was subjected to quantitative trait loci analysis [25].
We also compared the behavioral quantitative trait locus to those previously identified that are involved in regulating central nervous system neurotensin levels and neurotensin receptor densities [26].
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 [27].
Detection of quantitative trait Loci causing abnormal spermatogenesis and reduced testis weight in the small testis (Smt) mutant mouse [28].

Associations of Quantitative Trait Loci with chemical compounds

Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats [29].
FXR and ABCG5/ABCG8 as determinants of cholesterol gallstone formation from quantitative trait locus mapping in mice [30].
Domestication quantitative trait loci in Triticum dicoccoides, the progenitor of wheat [31].
Recently, a quantitative-trait locus (QTL) for whole blood serotonin level was identified in a genomewide linkage and association study in a founder population [32].
Quantitative trait loci and metabolic pathways: genetic control of the concentration of maysin, a corn earworm resistance factor, in maize silks [33].

Gene context of Quantitative Trait Loci

An 80-fold difference in expression of the mitochondrial uncoupling gene (Ucp1) at the mRNA and protein levels between A/J and C57BL/6J (B6) mice is controlled by allelic interactions among nine quantitative trait loci (QTLs) on eight chromosomes [34].
RESULTS: We identified a total of 12 separate quantitative trait loci (QTL) associated with PGIA, which we have named Pgia1 through Pgia12 [35].
Quantitative trait loci (QTL) linkage analysis using a B6AF(1) x C57BL/6J backcross population verified Aod1 and Aod2 that were previously mapped as qualitative traits [36].
We recently identified Prdx6 as a candidate for the quantitative trait locus Ath1, a gene responsible for a difference in diet-induced atherosclerosis susceptibility in mice [37].
Genetic and molecular analyses of natural variation indicate CBF2 as a candidate gene for underlying a freezing tolerance quantitative trait locus in Arabidopsis [38].

Analytical, diagnostic and therapeutic context of Quantitative Trait Loci

Via quantitative trait locus mapping followed by a candidate gene strategy using both mutant mice and pharmacological tools, we now demonstrate that the melanocortin-1 receptor (Mc1r) gene mediates kappa-opioid analgesia in female mice only [39].
None of the halothane-sensitivity quantitative trait loci significantly affected behavior in the absence of halothane or halothane's potency for C. elegans immobilization, which requires 5-fold higher drug concentrations [40].
The genetic dissection of PKD allowed us to map on rat chromosome 5, a quantitative trait locus (QTL) controlling PKD, kidney mass and plasma urea concentration [41].
We performed a quantitative trait locus (QTL) analysis of an F(2) cross between susceptible C57BL/6J (Ahr(b1) allele) and the highly resistant DBA/2 (Ahr(d) allele) strains after treatment with dioxin and iron [42].
In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures [43].

References

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Detection of quantitative trait Loci causing abnormal spermatogenesis and reduced testis weight in the small testis (Smt) mutant mouse. Bolor, H., Wakasugi, N., Zhao, W.D., Ishikawa, A. Exp. Anim. (2006) [Pubmed]
Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats. Aitman, T.J., Gotoda, T., Evans, A.L., Imrie, H., Heath, K.E., Trembling, P.M., Truman, H., Wallace, C.A., Rahman, A., Doré, C., Flint, J., Kren, V., Zidek, V., Kurtz, T.W., Pravenec, M., Scott, J. Nat. Genet. (1997) [Pubmed]
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Domestication quantitative trait loci in Triticum dicoccoides, the progenitor of wheat. Peng, J., Ronin, Y., Fahima, T., Röder, M.S., Li, Y., Nevo, E., Korol, A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
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Quantitative trait loci and metabolic pathways: genetic control of the concentration of maysin, a corn earworm resistance factor, in maize silks. Byrne, P.F., McMullen, M.D., Snook, M.E., Musket, T.A., Theuri, J.M., Widstrom, N.W., Wiseman, B.R., Coe, E.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
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