GENOMIC STRUCTURE AND ORGANIZATION OF THE HUMAN RBAT GENE (SLC3A1)

Cystinuria is an autosomal recessive disorder of amino acid transport, manifesting as three phenotypes (I, II, and III). An amino acid trans port gene, rBAT, is responsible for cystinuria, Mutation and linkage a nalyses have demonstrated the disease to be heterogeneous, with rBAT b eing the defective gene in type I cystinuria, The genomic structure of the human rBAT gene (HGMW-approved symbol SLC 3A1) has been establish ed via two strategies: (i) construction of two different genomic libra ries by subcloning the Mega-YAC921B6 (CEPH), containing rBAT, in Lambd a ZAP and screening using rBAT cDNA and different PCR products; and (i i) generation and sequencing of genomic fragments by long PCR using rB AT cDNA-derived primers, The rBAT gene spans approximately 45 kb and c onsists of 10 exons, The introns range from 500 to 13,000 bp. All spli ce sites conform to the GT/AG rule. The promoter region has been furth er analyzed, and a predicted TATA box 98 bp upstream of the first codi ng ATG was identified, In addition an Alu repeat has been detected 72 bp upstream of the predicted TATA box. (C) 1996 Academic Press, Inc.