Gene expression arrays
Figure 11.3 Recombinant inbred lines for mapping expression quantitative trait loci. A pair of chromosomes is shown for each of two parental inbred strains from whom recombinant inbred lines are generated by repeated sib mating. This produces mosaics of the original parental genomes and definition of underlying important genetic variation when integrated with gene expression profiling data. Reprinted by permission from Macmillan Publishers Ltd: Nature Genetics (Broman 2005), copyright 2005.
Such studies have been very important in advancing our understanding of this field and the underlying complexities of genetic variation modulating gene expression. The further work of Kruglyak and colleagues in yeast, for example, highlighted the large range of variance explained by genetic variation, even for highly heritable traits, with a median of 27% reported (Brem and Kruglyak 2005). Large effects of eQTLs appear rare with the majority of transcripts mapping to weak eQTLs. Inheritance is complex with only 3% of highly heritable transcripts showing linkage consistent with a single locus; for half of such transcripts, modelling suggests more than five eQTLs are involved (Brem and Kruglyak 2005). It was also striking that interactions between eQTLs are a prominent feature on the analysis of yeast when a two stage approach is taken, analysing primary then secondary eQTLs with such pairs of loci involved in inheritance of 57% of transcripts (Brem et al. 2005). Such epistatic effects (Section 13.2.3) are important and care is needed in the choice of analytical approach as the effects seen with the secondary loci were modest, and two-thirds would not be detected without the two stage approach (Brem et al. 2005).
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