HUMAN MUTATION 28(5), 441^450, 2007 443 TABLE 1. Diversity Indices and Di¡erent Estimators of Y (for a Sample of 80 InitiallyAscertained Chromosomes) BTN3A2 CAT CCND1 CCNE1 CDC25A CDKN1A CDKN1B CDKN2A CX3CR1 E2F1 FEN1 FGB GPX2 GPX3 GSS GSTM3 GSTM4 GSTP1 HDAC1 HTR2A IL1A MICA RB1 SKP2 SMAD3 SMAD4 TFDP1 TGFB1 k 9 8 11 3 7 13 11 7 17 5 6 11 17 10 9 7 9 12 11 13 4 17 6 3 5 2 4 9 S 14 7 13 2 7 11 10 8 16 4 5 13 16 11 9 6 10 13 12 18 3 15 5 2 5 2 8 9 G 0.57 0.74 0.62 0.10 0.34 0.76 0.78 0.35 0.86 0.43 0.55 0.80 0.74 0.64 0.73 0.70 0.73 0.71 0.67 0.71 0.67 0.87 0.44 0.10 0.72 0.03 0.28 0.62 L 2032 2092 1606 844 1664 1597 2012 2069 1987 1925 1992 1951 2077 2157 1931 1951 1780 2060 2029 2053 2008 2164 1963 1934 1366 1725 939 2012 d (%) 1.09 1.81 1.28 1.25 1.69 1.53 1.29 0.90 1.25 1.09 0.86 0.91 0.90 1.05 1.26 1.09 1.11 1.38 1.55 1.58 1.26 2.12 0.98 1.00 1.53 1.03 1.92 1.31 YS 2.84 1.41 2.62 0.40 1.41 2.22 2.02 1.61 3.23 0.81 1.01 2.62 3.23 2.25 1.82 1.21 2.02 2.62 2.42 3.63 0.60 3.04 1.01 0.40 1.01 0.40 1.62 1.82 Yp 2.20 1.65 1.43 0.10 0.38 3.18 1.60 0.58 4.03 0.48 0.61 2.06 2.27 2.61 1.59 1.38 2.14 4.11 1.03 2.39 0.99 1.61 0.53 0.10 1.32 0.05 0.83 2.18 YH 5.62 0.69 0.99 0.00 0.01 2.58 0.42 0.03 6.07 0.08 0.30 1.72 2.98 7.61 2.45 3.99 1.59 5.10 2.39 6.84 0.31 0.26 0.06 0.00 0.32 0.00 0.05 1.74 5 1 3 1 3 0 2 2 2 2 3 5 6 2 3 2 2 0 5 6 0 5 1 0 0 2 0 4 YF Yhom 0.98 2.17 1.25 0.08 0.37 2.42 2.74 0.41 5.01 0.55 0.91 3.09 2.17 1.31 2.11 1.82 2.05 1.89 1.52 1.83 1.58 5.38 0.59 0.08 1.94 0.02 0.29 1.25 Yk 2.42 2.02 3.23 0.46 1.66 4.16 3.23 1.66 6.32 1.01 1.32 3.23 6.32 2.89 2.40 1.66 2.40 3.68 3.23 4.16 0.73 6.41 1.32 0.46 1.01 0.22 0.73 2.42 Ma 5 1 1 0 0 2 1/0 0 6 0 0 1 2 6 2 3 1 5 2 5 0 0 0 0 0 0 0 2 aNumber of mutational steps from ancestral to the observed major haplotype (i.e., allelic class of the most frequent haplotype). b(1) indicates the presence of only one recombinant haplotype (see Supplementary Fig.1). cLevel of signi¢cance as from ARLEQUIN; FST values were calculated for an extended sample of 80 genotyped individuals. Po0.05. Po0.01. Po0.001. ns, not signi¢cant. Fst (%)c Four- gamete testb Total sample Non- African sample (1) (1) 1 1 1 1 (1) 1 1 (1) ns 7.9 ns ns 7.5 3.7 7.5 7.1 11.4 ns 18.7 11.4 15.1 7.4 3.4 9.3 ns 5.7 18.6 1.9 13.5 3.5 3.9 3.7 ns 7.7 10.6 ns ns 8.5 ns ns 8.2 ns 6.9 6.7 7.8 ns 9.8 9.9 18.5 ns ns 6.4 ns 2.1 ns ns 4.7 3.9 ns ns ns ns 7.0 ns v. 7.1 (StatSoft Inc., Tulsa, OK) were used to evaluate distributions and in correlation analyses. Coalescent simulations [Hudson, 1990] were performed under a selectively neutral model using the Cosi program of Schaffner et al. [2005] (www.broad.mit.edu/personal/sfs/cosi). We carried out these simulations using mutation rates defined by the average polymorphic site’s density and N 5 10,000 to obtain distributions of: 1) the number of haplotypes carrying distinct numbers (m 5 0, 1, 2, etc.) of new alleles; 2) the frequencies of the ancestral haplotypes; and 3) the major haplotypes among different classes of haplotypes defined by the number of new alleles, m, that they carry. In addition to simulations under the standard model without recombination, we studied the effect of recombinations, as well as demographic expansion and/or population bottleneck as used by Akey et al. [2004]. RESULTS Diversity Data In a group of 28 protein-coding genes (Supplementary Table S1), we characterized genetic variations in their promoter regions, defined arbitrarily as 2-kb segments upstream of the transcription start sites [see Kim et al., 2005]. Transcriptional start sites were defined based on the mRNA sequence versions (REFSEQ) listed in Supplementary Table S1. DNA polymorphisms were first ascertained by dHLPC, combined with DNA sequencing, in a panel of 40 genomic samples representing individuals of sub- Saharan African, Native American, European, Middle Eastern, and Southeast/East Asian descent [Sinnett et al., 2006]. All variants reported here were genotyped and thus independently reconfirmed by ASO hybridization in the same panel of 40 individuals. We observed 254 simple polymorphisms, 243 sub- stitutions, and 11 indels. The sequence contexts of each of the reported polymorphisms, as well as their ‘‘rs’’ identifiers, are provided in Supplementary Table S2, while the corresponding reconstructed haplotypes (see Materials and Methods) are listed in Supplementary Table S3. HWE was primarily tested as an additional means of checking the quality and consistency of our genotypes [e.g., Fan et al. 2002]. As a result, and after correcting for multiple testing [Storey, 2002] (see Materials and Methods), we found three polymorphisms in the CX3CR1 segment showing significant departure from the HWE (see below). Different diversity indices and other characteristics of the analyzed loci are presented in Table 1, which also includes per segment Fst values for the whole population sample and considering only non-African groups. Geographic distribution of haplotypes is given within haplotype networks shown in Supplementary Figure S1. On average, we observed nine segregating sites (S 5 9.174.6) and a similar number of haplotypes Human Mutation DOI 10.1002/humu