CRHR1 is located in a region, 17q21.31, which was recently described (Pennisi, 2008) as “one of the most structurally complex and evolutionarily dynamic regions of the genome.” A nearby gene, microtubule-associated protein tau (MAPT), first (Hutton et al. 1998) drew research attention to this area as a result of accumulating evidence (Pittman et al. 2006; Pastor et al. 2004) for association with risk of progressive supranuclear palsy (PSP), a neurodegenerative disease in which tau-positive neurofibrillary tangles are present. Additional examination (Pastor et al. 2004; Stefansson et al. 2005) revealed the existence of an extremely large linkage disequilibrium (LD) block spanning ~1.5 Mb extending across 5 adjacent genes (including MAPT and CRHR1). Two haplotypes, termed H1 and H2, have been described; the H2 haplotype contains an ~970 kb inversion that prevents recombination in H1/H2 heterozygotes (Stefansson et al. 2005). The H1 haplotype, present in all populations [H2 is found predominately in those of European ancestry (Stefansson et al. 2005)], is associated with increased risk for PSP and other neurologic disorders (Pastor et al. 2004; Skipper et al. 2004; Cruts et al.
