Behavior Genetics

, 36:248 | Cite as

Identification of QTLs Influencing Alcohol Preference in the High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) Mouse Lines

  • Paula J. Bice
  • Tatiana Foroud
  • Lucinda G. Carr
  • Lili Zhang
  • Lixiang Liu
  • Nicholas J. Grahame
  • Lawrence Lumeng
  • Ting-Kai Li
  • John K. Belknap
Article

 

The High- and Low-Alcohol Preferring (HAP1/LAP1 and HAP2/LAP2) mouse lines were developed by selective breeding for differences in alcohol preference. They represent the only extant selectively bred mouse lines developed for this alcohol phenotype. Therefore, they provide a unique resource for QTL detection and mapping. Importantly, neither of the replicate lines is inbred and therefore, novel study designs can be employed to detect loci contributing to alcohol preference. Two independent studies, with very different approaches, were conducted in the HAP and LAP replicate lines. In Study 1, microsatellite markers were genotyped in the replicate HAP1/LAP1 and HAP2/LAP2 mice in QTL regions nominated by other mouse RI and F2 studies in order to detect divergence of allele frequencies in the two oppositely selected lines. Significant differences in allele frequencies were observed in the HAP1/LAP1 mice with markers on chromosome 9 (p<0.01). In the HAP2/LAP2 mice, significant differences in allele frequencies were identified on chromosomes 2 and 9 (p<0.01). In Study 2, a genome-wide screen was performed in a sample of 432 HAP1×LAP1 F2 animals and a QTL on chromosome 9 (LOD=5.04) was found which met criteria for genome wide significance (p<0.001). Gender specific analyses supported a greater effect of the QTL among female mice (LOD=5.19; p<0.0008) than male mice (LOD=1.19). This study provides additional evidence and confirmation that specific regions on chromosomes 9 and perhaps 2 are important for alcohol preference.

Keywords

Alcohol preference HAP and LAP mice QTL selective breeding 

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Paula J. Bice
    • 1
    • 6
  • Tatiana Foroud
    • 2
  • Lucinda G. Carr
    • 1
  • Lili Zhang
    • 1
  • Lixiang Liu
    • 2
  • Nicholas J. Grahame
    • 3
  • Lawrence Lumeng
    • 1
  • Ting-Kai Li
    • 4
  • John K. Belknap
    • 5
  1. 1.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of PsychologyIndiana University Purdue University at IndianapolisIndianapolisUSA
  4. 4.National Institute of Alcohol Abuse and AlcoholismBethesdaUSA
  5. 5.VA Medical Center (R&D5), and Department of Behavioral NeuroscienceOregon Health & Science UniversityPortlandUSA
  6. 6.Department of MedicineIndiana University School of MedicineIndianapolisUSA

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