THE HUMAN CYSTATHIONINE BETA-SYNTHASE (CBS) GENE - COMPLETE SEQUENCE,ALTERNATIVE SPLICING, AND POLYMORPHISMS

Cystathionine P-synthase [CBS; L-serine hydro-lyase (adding homocystei ne), EC 4.2.1.22] catalyzes the first committed step of transsulfurati on and is the enzyme deficient in classical homocystinuria, In this re port, we describe the molecular cloning and the complete nucleotide se quence of the human CBS gene. We report a total of 28,046 nucleotides of sequence, which, in addition to the CBS gene, contains similar to 5 kb of the 5' flanking region. The human CBS gene contains 23 exons ra nging from 42 to 209 bp. The 5' UTR is formed by 1 of 5 alternatively used exons and 1 invariably present exon, while the 3' UTR is encoded by exons 16 and 17. We also describe the identification of two alterna tively used promoter regions that are GC rich (similar to 80%) and con tain numerous putative binding sites for Sp1, Ap1, Ap2, and c-myb, but lack the classical TATA box. The CBS locus contains an unusually high number of Alu repeats, which may predispose this gene to deleterious rearrangements. Additionally, we report on a number of DNA sequence re peats that are polymorphic in North American and European Caucasians, (C) 1998 Academic Press.