The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection.

Searching for genomic evidence of positive selection has been hailed as an attractive strategy for identifying functional polymorphisms. Here, we demonstrate the feasibility of identifying functional polymorphism at the MRP1 gene locus using this strategy. The 190 kDa MRP1 protein is an efflux pump that regulates the accumulation of xenobiotics and drugs in cells. Functional sequence variations within this gene might account, in part, for inter-individual and population differences in drug response. To identify single nucleotide polymorphisms (SNPs) within the MRP1 gene with potentially important functional significance, we scanned for genomic signatures of recent positive selection at this locus in approximately 480 individuals sampled from the Chinese, Malay, Indian, European-American and African-American populations. The genetic profile of SNPs at this locus revealed high haplotype diversity and weak linkage disequilibrium (LD). Despite this weak LD, major allele G of SNP 5'FR/G-260C contained within a high frequency haplotype exhibited extended haplotype homozygosity across 135 kb in European-Americans. Using two independent genomic tests, long-range haplotype (LRH) test and the F(ST) statistic, we found statistical evidence of positive selection for this allele in the European-American population. When this SNP was recapitulated in an in vitro MRP1 promoter-reporter assay, significantly lower activity was observed from the G-containing promoter when compared with the C-containing promoter in all four cell lines that we tested (P<0.01). These observations confirm the power of this strategy in identifying functionally different alleles of genes and suggest that the different alleles at this SNP locus in the MRP1 gene may account, in part, for inter-individual variations and population differences in drug response.[1]

References

  1. A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Wang, Z., Wang, B., Tang, K., Lee, E.J., Chong, S.S., Lee, C.G. Hum. Mol. Genet. (2005) [Pubmed]
 
WikiGenes - Universities