The Genom of Homo sapiens.pdf

HAPLOTYPE EXPRESSION ASSOCIATIONS 93multiple comparison corrected p value for this associationis 0.0025 (i.e., –10 log [0.0025] = 26).A total of 19 of the 22 genes had data in the replicationset. Of these, the most significant marker in the originaldata set was also significant in the replication set in sevencases (AIM1, CHKL, DDX17, DDX3, DNM1L, MUT,and PLEK). All but one of the genes (UROD) had at leastone significant marker in the replication set. Most ofthese markers are simple (1 or 2 SNPs) and most have arelatively good balance between the number of individualsin the Marker(+) and Marker(–) groups.Many individual SNPs in these genes displayed strongassociations (raw p≤0.001) with the corresponding expressionlevels. These are summarized in Table 2. This tablegives the gene, the location of the SNP, the allele frequency,and significance scores in the original and replicationsets. It also indicates genes for which we observed asignificant association with more than one of the probes forthat gene on the Affymetrix HG-U133A chip. For SNPs,12 genes showed significant associations with at least oneSNP in both the original and replication sets (AIM1,DDX17, ENTPD1, HBS1L, HMG14, LOC51103, MUT,PEX6, PLEK, RNPS1, UROD, and VAMP8). When wecombine the haplotype and single SNP markers, there isstrong evidence for replicated significant associations in 15of the 22 genes (AIM1, CHKL, DDX17, DDX3, DNM1L,ENTPD1, HBS1L, HMG14, LOC51103, MUT, PEX6,PLEK, RNPS1, UROD, and VAMP8), and there is moderateevidence in an additional 4 genes.trans-Acting Variation in a TranscriptionFactor: ZNF295To find potential novel transcription factors, we lookedfor gene loci whose variants were associated with differentialexpression of a much larger number of genes thana typical locus. One of the most extreme cases we foundwas the gene ZNF295 (GenBank accession AP001745.1),which codes for a largely uncharacterized zinc finger protein.We saw 1,291 unique associations with ZNF295with permutation-corrected p values