Abstract: Genome-wide association studies (GWAS) was recently used to identify SNPs in a genomic region on chromosome 4 that associate with serum urate levels and gout. The present disclosure shows that human ATP-binding cassette, subfamily G, 2 (ABCG2), encoded by the ABCG2 gene contained in this region, is a hitherto unknown urate efflux transporter. The present disclosure further shows that native ABCG2 is located in the brush border membrane of kidney proximal tubule cells, where it mediates renal urate secretion. Introduction of the mutation Q141K encoded by the common SNP rs2231142 by site-directed mutagenesis resulted in reduced urate transport rates compared to wild-type ABCG2. Data from a population-based study of 14,783 individuals support rs2231142 as the causal variant in the region and show highly significant associations with urate levels and gout.

Abstract: Genome-wide association studies (GWAS) was recently used to identify SNPs in a genomic region on chromosome 4 that associate with serum urate levels and gout. The present disclosure shows that human ATP-binding cassette, subfamily G, 2 (ABCG2), encoded by the ABCG2 gene contained in this region, is a hitherto unknown urate efflux transporter. The present disclosure further shows that native ABCG2 is located in the brush border membrane of kidney proximal tubule cells, where it mediates renal urate secretion. Introduction of the mutation Q141K encoded by the common SNP rs2231142 by site-directed mutagenesis resulted in reduced urate transport rates compared to wild-type ABCG2. Data from a population-based study of 14,783 individuals support rs2231142 as the causal variant in the region and show highly significant associations with urate levels and gout.

Abstract: The invention relates to compositions and methods of treating cystic fibrosis. More specifically, this invention relates to the use the AAV vectors and constructs to provide gene therapy to cystic fibrosis patients.

Abstract: Cystic fibrosis (CF) is the most common fatal autosomal recessive disease in the U.S. and is principally caused by the DF508 mutation the CFTR gene. The principal site of morbidity and mortality for this disease is the lung. We have used genomic and proteomic methods to identify ubiquitin carboxy terminal hydrolase-1 (UCHL1) as a biomarker for cystic fibrosis. Both gene expression and cognate protein expression are massively upregulated in CF lung epithelial cells. We suggest that this gene can be useful in the assembly of a diagnostic or prognostic chip for CF, or as a target for therapeutic intervention.