A New Standard Genetic Map for the Laboratory Mouse

Cox, Allison; Ackert‐Bicknell, Cheryl; Dumont, Beth L.; Ding, Yueming; Bell, Jordana T.; Brockmann, Gudrun A.; Wergedal, Jon E.; Bult, Carol J.; Paigen, Beverly; Flint, Jonathan; Tsaih, Shirng‐Wern; Churchill, Gary A.; Broman, Karl W.

doi:10.1534/genetics.109.105486

Cited by 211 publications

(285 citation statements)

References 41 publications

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“…The introgressed region of the B6.D2 Csnk1e line spanned 78-86.8 Mb whereas for the D2.B6 Csnk1e line spanned 78.7-81.6 Mb. The latter region was estimated to be B0.56 cM (Cox et al, 2009). As expected, the results of the SNP array confirmed that each congenic line contained o1% RH.…”

Section: Reciprocal Congenic Regionssupporting

confidence: 82%

Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Bryant

Parker

Zhou

et al. 2011

Neuropsychopharmacol

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Csnk1e, the gene encoding casein kinase 1-epsilon, has been implicated in sensitivity to amphetamines. Additionally, a polymorphism in CSNK1E was associated with heroin addiction, suggesting that this gene may also affect opioid sensitivity. In this study, we first conducted genome-wide quantitative trait locus (QTL) mapping of methamphetamine (MA)-induced locomotor activity in C57BL/6J (B6) Â DBA/ 2J (D2)-F 2 mice and a more highly recombinant F 8 advanced intercross line. We identified a QTL on chromosome 15 that contained Csnk1e (63-86 Mb; Csnk1e ¼ 79.25 Mb). We replicated this result and further narrowed the locus using B6.D2 Csnk1e and D2.B6 Csnk1e reciprocal congenic lines (78-86.8 and 78.7-81.6 Mb, respectively). This locus also affected sensitivity to the m-opioid receptor agonist fentanyl. Next, we directly tested the hypothesis that Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Mice harboring a null allele of Csnk1e showed an increase in locomotor activity following MA administration. Consistent with this result, coadministration of a selective pharmacological inhibitor of Csnk1e (PF-4800567) increased the locomotor stimulant response to both MA and fentanyl. These results show that a narrow genetic locus that contains Csnk1e is associated with differences in sensitivity to MA and fentanyl. Furthermore, gene knockout and selective pharmacological inhibition of Csnk1e define its role as a negative regulator of sensitivity to psychostimulants and opioids.

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Section: Reciprocal Congenic Regionssupporting

confidence: 82%

Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Bryant

Parker

Zhou

et al. 2011

Neuropsychopharmacol

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“…The marker map file was created using marker position data provided by GeneSeek. Marker positions in National Center for Biotechnology Information Build 37 were converted to genetic distances in sex-averaged centimorgans using the Jackson Laboratory's Mouse Map Converter tool (http://cgd.jax.org/mousemapconverter/) (40,41). The genetic map of the markers used for analysis was plotted using the plot.map function in R/ qtl.…”

Section: Methodsmentioning

confidence: 99%

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

Swaggart¹,

Demonbreun²,

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

123

161

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Many monogenic disorders, including the muscular dystrophies, display phenotypic variability despite the same disease-causing mutation. To identify genetic modifiers of muscular dystrophy and its associated cardiomyopathy, we used quantitative trait locus mapping and whole genome sequencing in a mouse model. This approach uncovered a modifier locus on chromosome 11 associated with sarcolemmal membrane damage and heart mass. Whole genome and RNA sequencing identified Anxa6, encoding annexin A6, as a modifier gene. A synonymous variant in exon 11 creates a cryptic splice donor, resulting in a truncated annexin A6 protein called ANXA6N32. Live cell imaging showed that annexin A6 orchestrates a repair zone and cap at the site of membrane disruption. In contrast, ANXA6N32 dramatically disrupted the annexin A6-rich cap and the associated repair zone, permitting membrane leak. Anxa6 is a modifier of muscular dystrophy and membrane repair after injury.dystrophin | muscle | plasma membrane

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“…We used the genetic distance estimates from the reference panel described in Cox et al (2009). These estimates were retrieved from the Mouse Map Converter hosted at Jackson Laboratories (http://cgd.jax.org/mousemapconverter).…”

Section: Genotype Imputationmentioning

confidence: 99%

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

et al. 2014

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Genetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F 2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F 2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F 2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of "realized relatedness." QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F 2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL.

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A New Standard Genetic Map for the Laboratory Mouse

Cited by 211 publications

References 41 publications

Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

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