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Further studies on using multiple-cross mapping (MCM) to map quantitative trait loci

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Abstract

We have completed whole-genome scans for quantitative trait loci (QTLs) associated with acute ethanol-induced activation in the six F2 intercrosses that can be formed from the C57BL/6J (B6), DBA/2J (D2) , BALB/cJ (C), and LP/J (LP) inbred strains. The goal was to test the hypothesis that given the relatively simple structure of the laboratory mouse genome, the same QTLs will be detected in multiple crosses which in turn will provide support for the strategy of multiple-cross mapping (MCM). QTLs with LOD scores greater than 4 were detected on Chrs 1, 2, 3, 8, 9, 13, 14, and 16. Only for the QTL on distal Chr 1 was there convincing evidence that the same or at least a very similar QTL was detected in multiple crosses. We also mapped the Chr 2 QTL directly in heterogeneous stock (HS) animals derived from the four inbred strains. At G19 the QTL was mapped to an approximately 3-Mbp interval and this interval was associated with a haplotype block with a largely biallelic structure: B6-L:C-D2. We conclude that mapping in HS animals not only provides significantly greater QTL resolution, at least in some cases it provides significantly more information about the QTL haplotype structure.

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Acknowledgments

This study was supported in part by grants from the National Institutes of Health AA11034, AA 13484, MH 51372, and the Veterans Affairs Research Service.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, 97239-3098, USA

    Barry Malmanger, Maureen Lawler, Shannon Coulombe, Rochelle Murray, Staci Cooper, Yekaterina Polyakov, John Belknap & Robert Hitzemann

  2. Research Service, Veterans Affairs Medical Center, Portland, Oregon, 97239, USA

    Barry Malmanger, Maureen Lawler, Shannon Coulombe, Rochelle Murray, Staci Cooper, Yekaterina Polyakov, John Belknap & Robert Hitzemann

  3. Department of Behavioral Neuroscience, L-470, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA

    Robert Hitzemann

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  1. Barry Malmanger
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Correspondence to Robert Hitzemann.

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Malmanger, B., Lawler, M., Coulombe, S. et al. Further studies on using multiple-cross mapping (MCM) to map quantitative trait loci. Mamm Genome 17, 1193–1204 (2006). https://doi.org/10.1007/s00335-006-0070-2

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