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Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis

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Abstract

The set of LXS recombinant inbred (RI) strains is a new and exceptionally large mapping panel that is suitable for the analysis of complex traits with comparatively high power. This panel consists of 77 strains—more than twice the size of other RI sets— and will typically provide sufficient statistical power (β = 0.8) to map quantitative trait loci (QTLs) that account for ∼25% of genetic variance with a genomewide p < 0.05. To characterize the genetic architecture of this new set of RI strains, we genotyped 330 MIT microsatellite markers distributed on all autosomes and the X Chromosome and assembled error-checked meiotic recombination maps that have an average F2-adjusted marker spacing of ∼4 cM. The LXS panel has a genetic structure consistent with random segregation and subsequent fixation of alleles, the expected 3–4 × map expansion, a low level of nonsyntenic association among loci, and complete independence among all 77 strains. Although the parental inbred strains—Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS)—were derived originally by selection from an 8-way heterogeneous stock selected for differential sensitivity to sedative effects of ethanol, the LXS panel is also segregating for many other traits. Thus, the LXS panel provides a powerful new resource for mapping complex traits across many systems and disciplines and should prove to be of great utility in modeling the genetics of complex diseases in human populations.

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References

  • A Allan R Isaacson (1985) ArticleTitleEthanol-induced grooming in mice selectively bred for differential sensitivity to ethanol Behav Neural Biol 44 386–392 Occurrence Handle1:CAS:528:DyaL28Xks12qsQ%3D%3D Occurrence Handle4084184

    CAS  PubMed  Google Scholar 

  • DW Bailey (1971) ArticleTitleRecombinant inbred strains Transplantation 11 325–327 Occurrence Handle1:STN:280:CS6B2M3ptVE%3D Occurrence Handle5558564

    CAS  PubMed  Google Scholar 

  • DW Bailey (1981) Recombinant inbred strains and bilineal congenic strains HL Foster JD Small JG Fox (Eds) The Mouse in Biomedical Research Academic Press New York 223–239

    Google Scholar 

  • JK Belknap (1998) ArticleTitleEffect of within-strain sample size on QTL detection and mapping using recombinant inbred mouse strains Behav Genet 28 29–38 Occurrence Handle10.1023/A:1021404714631 Occurrence Handle1:STN:280:DyaK1c3jsVOhtQ%3D%3D Occurrence Handle9573644

    Article  CAS  PubMed  Google Scholar 

  • JK Belknap SR Mitchell LA O’Toole ML Helms JC Crabbe (1996) ArticleTitleType 1 and type 2 error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains Behav Genet 26 149–160 Occurrence Handle1:STN:280:BymB3cvit10%3D Occurrence Handle8639150

    CAS  PubMed  Google Scholar 

  • B Bennett M Beeson L Gordon TE Johnson (2002) ArticleTitleReciprocal congenics defining individual quantitative trait loci for sedative/hypnotic sensitivity to ethanol Alcohol Clin Exp Res 26 149–157 Occurrence Handle1:STN:280:DC%2BD383isFOgtw%3D%3D Occurrence Handle11964553

    CAS  PubMed  Google Scholar 

  • KW Broman LB Rowe GA Churchill K Paigen (2002) ArticleTitleCrossover interference in the mouse Genetics 160 1123–1131 Occurrence Handle11901128

    PubMed  Google Scholar 

  • W Cao T Burkholder L Wilkins AC Collins (1993) ArticleTitleA genetic comparison of behavioral actions of ethanol and nicotine in the mirrored chamber Pharmacol Biochem Behav 45 803–809 Occurrence Handle10.1016/0091-3057(93)90124-C Occurrence Handle1:CAS:528:DyaK3sXlvFOlsLo%3D Occurrence Handle8415818

    Article  CAS  PubMed  Google Scholar 

  • EJ Chesler JB Wang L Lu Y Qu KE Manly et al. (2003) ArticleTitleGenetic correlates of gene expression in recombinant inbred strains: A relational model system to explore neurobehavioral phenotypes Neuroinformatics 1 343–357 Occurrence Handle10.1385/NI:1:4:343 Occurrence Handle15043220

    Article  PubMed  Google Scholar 

  • AC Church JL Fuller L Dann (1979) ArticleTitleAlcohol intake in selected lines of mice: Importance of sex and genotype J Comp Physiol Psychol 93 242–246 Occurrence Handle1:STN:280:CSaB3Mnptl0%3D Occurrence Handle457948

    CAS  PubMed  Google Scholar 

  • JC DeFries JR Wilson VG Erwin DR Petersen (1989) ArticleTitleLS × SS recombinant inbred strains of mice: Initial characterization Alcohol Clin Exp Res 13 196–200 Occurrence Handle1:STN:280:BiaB2s%2FptlY%3D Occurrence Handle2658655

    CAS  PubMed  Google Scholar 

  • Deitrich RA, Pawlowski AA (1990) Initial sensitivity to alcohol. In: A Workshop on Alcohol Intoxication (Keystone, CO: U.S. Department of Health and Human Services, Public Health Service)

  • VG Erwin PD Markel TE Johnson VM Gehle BC Jones (1997) ArticleTitleCommon quantitative trait loci for alcohol-related behaviors and central nervous system neurotensin measures: Hypnotic and hypothermic effects J Pharmacol Exp Ther 280 911–918 Occurrence Handle1:CAS:528:DyaK2sXivVWqsrc%3D Occurrence Handle9023306

    CAS  PubMed  Google Scholar 

  • VM Gehle VG Erwin (2000) ArticleTitleThe genetics of acute functional tolerance and initial sensitivity to ethanol for an ataxia test in the LS × SS RI strains Alcohol Clin Exp Res 24 579–587 Occurrence Handle10.1097/00000374-200005000-00001 Occurrence Handle1:CAS:528:DC%2BD3cXktFGiurs%3D Occurrence Handle10832898

    Article  CAS  PubMed  Google Scholar 

  • EL Green (1981) Genetics and Probability in Animal Breeding Experiments Oxford University Press New York

    Google Scholar 

  • JBS Haldane CH Waddington (1931) ArticleTitleInbreeding and linkage Genetics 16 357–374 Occurrence Handle1:STN:280:Bi2B3c%2FotVM%3D Occurrence Handle7342407

    CAS  PubMed  Google Scholar 

  • GJ Huang JJ McArdle (1993) ArticleTitleChronic ingestion of ethanol increases the number of Ca2+ channels of hippocampal neurons of long-sleep but not short-sleep mice Brain Res 615 328–330 Occurrence Handle10.1016/0006-8993(93)90044-N Occurrence Handle1:CAS:528:DyaK3sXltlegsr4%3D Occurrence Handle8395960

    Article  CAS  PubMed  Google Scholar 

  • M Jirout D Krenova V Kren L Breen M Pravenec et al. (2003) ArticleTitleA new framework marker-based linkage map and SDPs for the rat HXB/BXH strain set Mamm Genome 14 537–546 Occurrence Handle10.1007/s00335-003-2266-z Occurrence Handle1:CAS:528:DC%2BD3sXmslCqt74%3D Occurrence Handle12925886

    Article  CAS  PubMed  Google Scholar 

  • D Lang M Beno E Fifkova H Eason (1997) ArticleTitleFine structure of hippocampal dendrites in the dentate fascia of LS/SS mice after chronic ethanol treatment Prog Neuropsychopharmacol Biol Psychiatry 21 1031–1042 Occurrence Handle10.1016/S0278-5846(97)00096-1 Occurrence Handle1:CAS:528:DyaK2sXmtVGjsb0%3D Occurrence Handle9380786

    Article  CAS  PubMed  Google Scholar 

  • IP Lapin S Mirzaev (1996) ArticleTitleThe contrary effects of ethanol on the behavior of short-and long-sleep C57BL/6 mice in a dark-light chamber Eksp Klin Farmakol 59 50–52 Occurrence Handle1:CAS:528:DyaK28XmtVWgtbw%3D Occurrence Handle8974567

    CAS  PubMed  Google Scholar 

  • L Lu DC Airey RW Williams (2001) ArticleTitleComplex trait analysis of the hippocampus: Mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice J Neurosci 21 3503–3514 Occurrence Handle1:CAS:528:DC%2BD3MXjs1ant7Y%3D Occurrence Handle11331379

    CAS  PubMed  Google Scholar 

  • M Lynch B Walsh (1998) Genetics and Analysis of Quantitative Traits Sinauer Associates, Inc. Sunderland, MA

    Google Scholar 

  • KF Manly JM Olson (1999) ArticleTitleOverview of QTL mapping software and introduction to Map Manager QT Mamm Genome 10 327–334 Occurrence Handle10.1007/s003359900997 Occurrence Handle1:CAS:528:DyaK1MXhvFyqtLY%3D Occurrence Handle10087288

    Article  CAS  PubMed  Google Scholar 

  • PD Markel JC DeFries TE Johnson (1995) ArticleTitleUse of repeated measures in ethanol-induced loss of righting reflex in inbred long-sleep and short-sleep mice Alcohol Clin Exp Res 19 299–304 Occurrence Handle1:CAS:528:DyaK2MXmtFygtrY%3D Occurrence Handle7625561

    CAS  PubMed  Google Scholar 

  • PD Markel DW Fulker B Bennett RP Corley JC DeFries et al. (1996) ArticleTitleQuantitative trait loci for ethanol sensitivity in the LS × SS recombinant inbred strains: Interval mapping Behav Genet 26 447–458 Occurrence Handle1:STN:280:BymA28jnvFU%3D Occurrence Handle8771905

    CAS  PubMed  Google Scholar 

  • J Markham E Fifkova A Scheetz (1987) ArticleTitleEffect of chronic ethanol consumption on the fine structure of the dentate gyrus in long-sleep and short-sleep mice Exp Neurol 95 290–302 Occurrence Handle10.1016/0014-4886(87)90139-7 Occurrence Handle1:CAS:528:DyaL2sXhtlemtbo%3D Occurrence Handle3803516

    Article  CAS  PubMed  Google Scholar 

  • GE McClearn R Kakihana (1981) Selective breeding for ethanol sensitivity: Short-sleep and long-sleep mice GE McClearn RA Deitrich VG Erwin (Eds) Development of Animal Models as Pharmacogenetic Tools U.S. Government Printing Office Washington, DC 81–113

    Google Scholar 

  • GE McClearn JR Wilson W Meredith (1970) The use of isogenic and heterogenic mouse stocks in behavioral research G Lindzey DD Thiessen (Eds) Contributions to Behavior–Genetic Analysis: The Mouse As a Prototype Appleton-Century-Crofts New York 3–22

    Google Scholar 

  • J Owens B Bennett TE Johnson (2002) ArticleTitlePossible pleiotropic effects of genes specifying sedative/hypnotic sensitivity to ethanol on other alcohol-related traits Alcohol Clin Exp Res 26 1461–1467 Occurrence Handle1:CAS:528:DC%2BD38XotVCmtrw%3D Occurrence Handle12394278

    CAS  PubMed  Google Scholar 

  • W Poelchen WR Proctor TV Dunwiddie (2000) ArticleTitleThe in vitro ethanol sensitivity of hippocampal synaptic gamma-aminobutyric acid (a) responses differs in lines of mice and rats genetically selected for behavioral sensitivity or insensitivity to ethanol J Pharmacol Exp 295 741–746 Occurrence Handle1:CAS:528:DC%2BD3cXnsl2kt7c%3D Occurrence Handle11046113

    CAS  PubMed  Google Scholar 

  • BA Rikke JE Yerg ME Battaglia TR Nagy DB Allison et al. (2003) ArticleTitleStrain variation in the response of body temperature to dietary restriction Mech Ageing Dev 124 663–678 Occurrence Handle10.1016/S0047-6374(03)00003-4 Occurrence Handle12735906

    Article  PubMed  Google Scholar 

  • BA Rikke JE Yerg ME Battaglia TR Nagy DB Allison et al. (2004) ArticleTitleQuantitative trait loci specifying the response of body temperature to dietary restriction J Gerontol 59A 11

    Google Scholar 

  • Stenehjem S, Bruggemann E (2001) Glume bar phenotypes in a b73 × mo17 recombinant inbred population reveal the epistatic interaction between p11 and b1. In: Marize Genetic Conference, 42nd Annual Marize Genetic Conference, Coeur d’Alene, ID (http://www.maizegdb.org/maize-meeting/2001/03abstracts.pdf, p 80)

  • A Stinchcomb BJ Bowers JM Wehner (1989) ArticleTitleThe effects of ethanol and ro 15-4513 on elevated plus-maze and rotarod performance in long-sleep and short-sleep mice Alcohol 5 369–376 Occurrence Handle10.1016/0741-8329(89)90006-2

    Article  Google Scholar 

  • KM Swanberg JR Wilson A Kalisker (1979) ArticleTitleDevelopmental and genotypic effects on pituitary–adrenal function and alcohol tolerance in mice Dev Psychobiol 12 201–210 Occurrence Handle1:CAS:528:DyaE1MXktFCqu7o%3D Occurrence Handle437360

    CAS  PubMed  Google Scholar 

  • BA Taylor (1978) Recombinant inbred strains: Use in gene mapping HC Morse (Eds) Origins of Inbred Mice Academic Press New York 423–435

    Google Scholar 

  • CM Wade EJ Kulbokas AW Kirby MC Zody JC Mullikin et al. (2002) ArticleTitleThe mosaic structure of variation in the laboratory mouse genome Nature 420 574–578 Occurrence Handle10.1038/nature01252 Occurrence Handle1:CAS:528:DC%2BD38Xpt1WhsL4%3D Occurrence Handle12466852

    Article  CAS  PubMed  Google Scholar 

  • GS Wand (1989) ArticleTitleEthanol differentially regulates proadrenocorticotropin/endorphin production and corticosterone secretion in LS and SS lines of mice Endocrinology 124 518–526 Occurrence Handle1:CAS:528:DyaL1MXntV2lsg%3D%3D Occurrence Handle2535813

    CAS  PubMed  Google Scholar 

  • GS Wand (1990) ArticleTitleDifferential regulation of anterior pituitary corticotrope function is observed in vivo but not in vitro in two lines of ethanol-sensitive mice Alcohol Clin Exp Res 14 100–106 Occurrence Handle1:CAS:528:DyaK3cXktVWru74%3D Occurrence Handle1689969

    CAS  PubMed  Google Scholar 

  • RW Williams J Gu S Qi L Lu (2001) ArticleTitleThe genetic structure of recombinant inbred mice: High-resolution consensus maps for complex trait analysis Genome Biol 2 IssueID11 46–46

    Google Scholar 

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Acknowledgments

We thank Jerome Salazar and Jean Wah for careful and reliable animal care and breeding and Eugene Thomas for the initial breeding. We also thank Nancy Phares–Zook for her research contributions and for her outstanding job managing our many diverse databases. Linda Lou Wessman, Justin Springett, and Jessica Hall cut many tails and extracted DNA. Lena Gordon ran numerous screening and confirmatory gels. We also thank our colleagues at IBG and elsewhere who gave advice throughout the study and in reading the many versions of the manuscript. We thank Shuhua Qi for excellent support in genotyping the LXS strains and Yanhua Qu for helping with the BLAT analysis of microsatellite sequences. Dr. Elissa Chesler patiently and on numerous occasions gave BB very thorough instruction on application and interpretation of R/qtl. This work was supported by grants from the NIH [RO1 AA11984-(TEJ) and KO1 AA00195 (TEJ) and P50 AA13755 (RWW)], by the Ellison Foundation for Medical Research (TEJ), and by funds from the University of Colorado. Genotyping costs were supported in part by P20-MH 62009 (a Human Brain Project to RWW) and the JNIA Genotyping Core (U24AA13513 to LL and RWW).

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(Robert W. Williams and Beth Bennett)These authors contributed equally to this work.

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Williams, R.W., Bennett, B., Lu, L. et al. Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis. Mamm Genome 15, 637–647 (2004). https://doi.org/10.1007/s00335-004-2380-6

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