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Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors

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Abstract

The objective of the present study was to map quantitative trait loci (QTL) for alcohol intake using A × B/B × A recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice that were independently derived from the A/J and C57BL/6J progenitors. Mice were screened for levels of alcohol consumption with four days of forced exposure to alcohol, followed by three weeks of free choice between water and a 10% alcohol solution. Alcohol consumption data previously collected for 27 A × B/B × A RI strains were reanalyzed using a larger marker set and composite interval mapping. The reanalysis found markers on Chromosome 2 (D2Mit74, 107 cM) (males and females) and on Chromosome 11 (Pmv22, 8 cM) (females only) that exceeded the threshold for significant loci, and found suggestive loci (in males) on Chromosomes 10 (D10 Mit126, 21 cM), 12 (D12Mit37, 1 cM), 15 (Pdgfb, 46.8 cM), and 16 (D16Mit125, 29 cM). An additional suggestive locus was identified in female RI mice on Chromosome 11 (D11Mit120, 47.5 cM). Composite interval mapping (CIM) analysis indicated that there was a significant association between loci at Pdgfb and D2Mit74 in both males and females. Analysis of the AcB/BcA RC strains identified 11 QTL on Chromosomes 2, 3, 5,6, 7, 8, 9, 10, 12, 13, and 15. QTL on Chromosomes 7, 10, 12, and 15 were identified in both the A × B/B × A RI and AcB/BcA RC strains of mice. Additional QTLs identified on Chromosomes 2, 3, 7, 11, and 15 overlap with those previously identified in the literature using strains of mice with a C57BL/6J progenitor.

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Abbreviations

VAC:

voluntary alcohol consumption

RI:

recombinant inbred

RC:

recombinant congenic

QTL:

quantitative trait locus

LRS:

likelihood ratio statistic

CIM:

composite interval mapping

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Acknowledgments

This research was supported by operating grants awarded to K. Gill by the Canadian Institutes of Health Research (CIHR) and the Alcohol Beverage Medical Research Foundation (ABMRF). The authors acknowledge Emerillon Therapeutics Inc. and Dr. E. Skamene, Director of the Research Institute of the McGill University Health Centre, for providing access to the AcB/BcA RC mice and genetic maps.

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  1. Research Institute of the McGill University Health Centre and Psychiatry Department, McGill University, Montreal, Quebec, Canada

    Kathryn Gill & Alan E. Boyle

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  1. Kathryn Gill
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  2. Alan E. Boyle
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Correspondence to Kathryn Gill.

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Gill, K., Boyle, A.E. Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors. Mamm Genome 16, 319–331 (2005). https://doi.org/10.1007/s00335-004-2239-x

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  • DOI: https://doi.org/10.1007/s00335-004-2239-x

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