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Chunk #11 — Methods — Computational haplotype-based genetic mapping

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From mouse to man: the 5-HT3 receptor modulates physical dependence on opioid narcotics.
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Haplotype-based computational genetic analysis of the phenotypic data was performed as previously described [11,14,24,25]. This technique has been used recently to identify genes associated with a number of different murine phenotypic traits including opioid narcotic drug responses [9,13-15]. In brief, allelic data from multiple inbred strains were analyzed and a haplotype block map of the mouse genome was constructed. Only a limited number of haplotypes – typically 2, 3, or 4 – are present within a haplotype block. This analysis identifies haplotype blocks in which the haplotypic strain grouping within a block correlates with the distribution of phenotypic data among the inbred strains analyzed. To do this, a P value that assesses the likelihood that genetic variation within each block could underlie the observed distribution of phenotypes among the inbred strains is calculated as described using analysis of variance [11,12]. The phenotypic data were evaluated using the average value for each strain, obtained by assessing eight mice per strain. The haplotype blocks are then ranked based upon the calculated P value. When this computational analysis was performed, the haplotype map