Quantitative Trait Loci Studies

These findings were unexpected because previous studies had demonstrated that the y2 subunit is required for potentiation of GABAa receptor function by low concentrations of ethanol [2]. The y2 subunit gene is located within a definitely mapped quantitative trait locus (QTL) for acute alcohol withdrawal on mouse chromosome 11 [1]. Allelic variation was genetically... 

A major problem of such approaches is that they have extremely low statistical power. For example, for a tightly linked marker (0 = 0) to trait-related locus which in turn accounts for as much as 15% of the variance in the quantitative trait (Fa = 0.15) Sham et al. (55) estimated that 5322 sib pairs would be needed. Although a number of twin cohorts with very extensive phenotyping exist (4) which could potentially be used for linkage studies, the low statistical power involved renders them less attractive for mapping QTLs. 

Each of the Quantitative Trait Loci (QTL) studies had unique features that maximised the potential for novel locus discovery but makes comparisons difficult. The first source of variation was the choice of mouse strains. Three different combinations were used CAST x NZW (F2 intercross) [55, 56], CAST x SJL (F2 intercross) [57] and C57 x RIII (reciprocal backcross and F2 intercross) [57, 59]. Using only two strains of mice in a cross simplifies the analysis but limits the number of potential alleles compared to those expected in an outbred population. The use of closely related laboratory strains also limits the potential for detecting variation. The second source of variation was the choice of prion strain. Across all... 

---