Quantitative trait loci for acute behavioral sensitivity to paraoxon

Risinger, Fred O.; Quick, Edwin; Belknap, John K.

doi:10.1016/s0892-0362(00)00085-4

Cited by 12 publications

(4 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This analysis provides a reason to suspect that variants in ELMOD1 may have downstream effects on higher order phenotypes. In support of this idea, four independent studies have shown that variation in locomotor activity maps to the ELMOD1 locus on chromosome 9 (GeneNetwork traits: GN10566 [23], GN11518 [24], GN10132 [25], and GN10010 [26]). Hearing sensitivity also maps to this region (GN10654), and ELMOD1 is a strong candidate gene for this trait given independent evidence that mutations in this gene cause hearing and balance deficits [27].…”

Section: Resultsmentioning

confidence: 90%

Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

Pandey

Wang

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes.

show abstract

Section: Resultsmentioning

confidence: 90%

Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

Pandey

Wang

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Zn concentration was correlated in QTL region on chromosome 8 in the NA of females and on chromosomes 3, 13, and 17 in males in PFC [18] Zinc b QTL on chromosome 9 was correlated with zinc content in the hippocampus [59] Diisopropyl fluorophosphate 4 mg/kg 21 differentially expressed genes having significant QTLs related to CORT + DFP [3] Paraoxon 0-1 mg/kg Paraoxon treatment reduced locomotor activity and this depression was dependent on the genotype [96] a: Doses needed to induce a running, bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. b: not informed.…”

Section: Discussionmentioning

confidence: 99%

“…The doses ranged between 0 and 1 mg/kg of paraoxon. The results showed that paraoxon treatment reduced locomotor activity in most but not all BXD strains, concluding that the magnitude of locomotor depression was dependent on the genotype [ 96 ].…”

Section: Pesticidesmentioning

confidence: 99%

BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity

et al. 2021

View full text Add to dashboard Cite

BXD recombinant inbred (RI) lines represent a genetic reference population derived from a cross between C57BL/6J mice (B6) and DBA/2J mice (D2), which through meiotic recombination events possesses recombinant chromosomes containing B6 or D2 haplotype segments. The quantitative trait loci (QTLs) are the locations of segregating genetic polymorphisms and are fundamental to understanding genetic diversity in human disease susceptibility and severity. QTL mapping represents the typical approach for identifying naturally occurring polymorphisms that influence complex phenotypes. In this process, genotypic values at markers of known genomic locations are associated with phenotypic values measured in a segregating population. Indeed, BXD RI strains provide a powerful tool to study neurotoxicity induced by different substances. In this review, we describe the use of BXD RI lines to understand the underlying mechanisms of neurotoxicity in response to ethanol and cocaine, as well as metals and pesticide exposures.

show abstract

“…This study was motivated by three factors: first, the results of human and animal studies show that females have higher PON1 activity levels than males [Kleemola et al, 2002;Mueller et al, 1983;Rainwater et al, 2005]; second, there is significant heritable component to variation in PON1 activity and concentrations [Rainwater et al, 2005;Risinger et al, 2000;Weber, 1995]; and third, QTLs, in addition to the PON1 structural locus, likely account for some of the variation in the activity of this enzyme [Winnier et al, 2006]. We detected evidence of G Â S interaction contributing to variation in PON1 activity and have localized this interaction to a QTL on chromosome 17, a chromosome other than the one harboring the structural locus.…”

Section: Discussionmentioning

confidence: 99%

Sex‐specific QTL effects on variation in paraoxonase 1 (PON1) activity in Mexican Americans

Winnier

Rainwater

Cole

et al. 2006

Genetic Epidemiology

View full text Add to dashboard Cite

Paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme known to protect against cellular damage from toxic agents, may also have antioxidant properties. PON1 activity levels have been reported to differ by sex in human and animal studies with females exhibiting higher basal levels. We measured PON1 activity frozen serum for 1,406 individuals in over 40 extended pedigrees from the San Antonio Family Heart Study (SAFHS). We used a maximum likelihood-based, variance decomposition approach implemented in SOLAR to test for genotype-by-sex (G x S) interaction on variation in PON1 activity and to determine if any of the four PON1 quantitative trait loci (QTL) previously reported by us for this population might account for sex differences in PON1 activity levels. The residual additive genetic correlation (rho(G) = 0.82) between males and females is significantly different from 1 (P = 0.009), suggesting that some of the genes that influence PON1 activity act differently in females and males or, possibly, that a different combination of genes influences this trait in each sex. In addition to the QTL at or near the PON structural locus on 7q21-22, three other potential QTLs were evaluated for sex-specific effects: one each on chromosomes 12, 17 and 19. The QTL on chromosome 17 (LOD = 2.32, P = 0.0003; flanked by microsatellite marker loci D17S974 and D17S969) shows a significant (P = 0.005) sex-specific effect on PON1 activity; accounting for 6% of the additive genetic variance in males and 20% in females. This study represents the first formal statistical genetic test for G x S interactions on normal quantitative variation in PON1 activity in humans.

show abstract

Quantitative trait loci for acute behavioral sensitivity to paraoxon

Cited by 12 publications

References 50 publications

Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity

Sex‐specific QTL effects on variation in paraoxonase 1 (PON1) activity in Mexican Americans

Contact Info

Product

Resources

About