Genomic Structure and Organization of the HumanrBATGene (SLC3A1)

Abstract

Cystinuria is an autosomal recessive disorder of amino acid transport, manifesting as three phenotypes (I, II, and III). An amino acid transport gene,rBAT,is responsible for cystinuria. Mutation and linkage analyses have demonstrated the disease to be heterogeneous, withrBATbeing the defective gene in type I cystinuria. The genomic structure of the humanrBATgene (HGMW-approved symbol SLC 3A1) has been established via two strategies: (i) construction of two different genomic libraries by subcloning the MegaYAC921B6 (CEPH), containingrBAT,in Lambda ZAP and screening usingrBATcDNA and different PCR products; and (ii) generation and sequencing of genomic fragments by long PCR usingrBATcDNA-derived primers. TherBATgene spans approximately 45 kb and consists of 10 exons. The introns range from 500 to 13,000 bp. All splice sites conform to the GT/AG rule. The promoter region has been further analyzed, and a predicted TATA box 98 bp upstream of the first coding ATG was identified. In addition anAlurepeat has been detected 72 bp upstream of the predicted TATA box.