To identify an appropriate control group for evaluating the frequency of W317X, we compared the genomewide genotyping data from the parents of the pedigree with data from 188 subjects of northern and western European (abbreviated as CEU), African, or Asian ancestry in the HapMap database, using a multidimensional scaling analysis.7 We found that the parents tightly cluster with CEU subjects (Fig. S1 in the Supplementary Appendix). Consequently, we genotyped 3000 control chromosomes from unrelated CEU persons. W317X was not found. Similarly, resequencing of the coding region of HDC in 720 patients with Tourette's syndrome and 360 controls not screened for psychiatric disorders revealed no additional nonsense variants and a total of three missense variants, one found in a patient and two in controls (Table S4 in the Supplementary Appendix). All were predicted, by means of standard bioinformatic algorithms (see the Supplementary Appendix), to affect protein function. Review of public databases identified one putative nonsense mutation, rs35490626; however, it did not meet validation criteria established by dbSNP, since it was not found in more than one sequence read and did not
