CSF CRH but increased plasma ACTH) are consistent with our in vitro findings, which demonstrated the loss of a GRE half-site and decreased sensitivity to corticosteroids. However, as we did not sequence beyond the boundaries of this haplotype, we do not know whether there is another functional marker in LD with -2232 G, nor do we know about the block size, which might provide further evidence for selection. That being said, several studies in humans 53, 54 have shown there to be evidence for selection at the CRH locus, in which, similar to the rhesus macaque, we have observed alternative, yin-yang haplotype clades (Figure 2). As in the rhesus macaque, the major human CRH haplotypes have been shown to vary in terms of their in vitro promoter activity, and among the observed differences are those pertaining to glucocorticoid-sensitivity20.
