The High- and Low-Alcohol Preferring (HAP and LAP) mouse lines have been selectively bred for differences in alcohol preference. These lines are the only extant selectively bred mouse lines developed for alcohol preference. Therefore, they provide a unique opportunity to potentially confirm the QTLs putatively identified in the BXD RI studies or confirmed in the F2 verification studies. These lines will also provide an opportunity to examine syntenic regions in the mouse where QTLs have been provisionally identified in the Alcohol-Preferring and Non- preferring (P and NP) rat lines and the High and Low-Alcohol Drinking (HAD and LAD) rat lines. Because linkage disequilibrium is expected to be restricted to small regions very close to a QTL (approximately 1 to 2 cM) in the selection lines, it will be necessary to use a high density of markers to detect QTLs in regions where they are known to exist from other studies. The purpose of this effort is to obtain confirmatory evidence for the existence of QTLs, and to obtain much higher mapping resolution than is possible in F2 after that of Belknap et al. (1997) Evidence for the presence of QTLs is gained whenever the allele frequencies at a marker diverse significantly more in the two oppositely- selected lines than is expected by genetic drift and allele frequency estimation error. We also propose a similar analysis in the second replicate set, (the HAP2/LAP2) line staring in the 2nd generation. This will allow us to examine the progression of changes in allele frequency as the animals are being selected. The heterogenous stock from which the HAP and LAP lines were derived will likely result in the detection and mapping of novel QTLs not segregating in other animal lines, such as those derived from B6 and D2 progenitors (e.g., the BXD RI strains). Thus, we also propose to do a fun genome screen to search for novel QTLs by using F2 animals generated from a HAP1 X LAP1 cross. We will initially perform linkage analyses for the HAP1 X LAP1 F2 animals using a novel method developed by Haley and Knott (1994), specifically designed for linkage analysis in non-inbred animal lines. In addition, we will use a program designed for marker map development in human studies to create rat marker maps (CRI-MAP; Green, 1990) and we will use a recently developed variance component linkage analysis method which may be used for quantitative traits (Almasy & Blangero, 1998).
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| Bice, Paula J; Foroud, Tatiana; Carr, Lucinda G et al. (2006) Identification of QTLs influencing alcohol preference in the High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) mouse lines. Behav Genet 36:248-60 |
