Twenty mutations at the rhesus CRH locus were in linkage disequilibrium (LD, D′) with -2232 C>G, and roughly 15% of individuals in the NIH population were heterozygous at these sites (MAF = 8%). Sequencing of the regions containing each polymorphic site in this haplotype demonstrated that these 21 markers were in perfect LD in multiple macaque populations, in which they also occurred at similar frequencies. Neutral sites in LD with an allele maintained by selection have a better chance of remaining in the population 51, 52. The persistence of the two divergent rhCRH haplotypes over time may suggest that they have been subject to selection such that at least one of the alleles on each background is being selected–possibly in a particular environmental context–while the rest are hitchhiking. The effects of the H2 haplotype on our intermediate phenotypes (i.e., decreased 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
