ABCA2 p.Ala1541Gly
| Predicted by SNAP2: | A: D (53%), C: D (53%), D: D (59%), E: N (53%), F: D (71%), G: D (63%), H: N (57%), I: D (59%), K: N (57%), L: D (63%), M: D (53%), N: N (57%), P: D (63%), Q: D (53%), R: D (59%), S: N (66%), V: D (53%), W: D (85%), Y: D (66%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, V: N, W: D, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Signatures of recent positive selection at the ATP... Hum Mol Genet. 2007 Jun 1;16(11):1367-80. Epub 2007 Apr 5. Wang Z, Wang J, Tantoso E, Wang B, Tai AY, Ooi LL, Chong SS, Lee CG
Signatures of recent positive selection at the ATP-binding cassette drug transporter superfamily gene loci.
Hum Mol Genet. 2007 Jun 1;16(11):1367-80. Epub 2007 Apr 5., [PMID:17412754]
Abstract [show]
Members of the ATP-binding cassette (ABC) superfamily of transporters have been implicated as major players in drug response. Single nucleotide polymorphisms (SNPs) in the ABC transporter genes may account for variation in drug response between individuals. Given the abundance of SNPs within the human genome, identification of functionally important SNPs is difficult. Here, we utilized signatures of recent positive selection (RPS) to identify SNPs in ABC genes that have potential functional significance by using the long-range-haplotype test to search for signatures of RPS at 18 ABC genes involved in drug transport. From the genotype data of these 18 ABC genes in four populations extracted from the HapMap database, at least one SNP in each of these genes displayed genomic signatures of RPS in at least one population. However, only 13 SNPs in 10 ABC genes from three populations retained statistical significance after Type I error reduction. The functional significance of six of these RPS SNPs, including those that failed multiple testing correction (MTC), has been reported previously. We experimentally confirmed a functional effect for two SNPs, including one that failed to show evidence of RPS after MTC. These observations suggest that Type I error reduction may inadvertently increase Type II error. Although the remaining positively selected SNPs have yet to be functionally validated, our study illustrates the feasibility of using this strategy to identify SNPs within 'adaptive' genes that may confer functional effect, prior to testing their roles in individual/population drug response variation or in complex disease susceptibility.
Comments [show]
None has been submitted yet.
No. Sentence Comment
66 Hence, a total of 32 SNPs were found to display RPS, most of them being selected only in a single population except for SNPs e35/T5562C in ABCA2, e21/G2677T/A in ABCB1, e9/C504T in ABCB4 and i1/T1541G and i14/A473C in ABCC11, which showed RPS in two populations (Table 2).
X
ABCA2 p.Ala1541Gly 17412754:66:194
status: NEW71 Interestingly, the major T and A alleles of SNPs i1/T1541G and i14/A473C, respectively, in ABCC11 that showed RPS in both the YRI and CEU (Table 2) were found to be fixed in the CHB and JPT (Supplementary Material, Table S2).
X
ABCA2 p.Ala1541Gly 17412754:71:52
status: NEW