The Human Cystathionine β-Synthase (CBS) Gene: Complete Sequence, Alternative Splicing, and Polymorphisms

• Published in: Genomics (San Diego, Calif.) Calif.), 1998-09, Vol.52 (3), p.312-324
• Main Authors: Kraus, Jan P., Oliveriusová, Jana, Sokolová, Jitka, Kraus, Eva, Vlček, Čestmı&́r, de Franchis, Raffaella, Maclean, Kenneth N., Bao, Liming, Bukovská, Gabriela, Patterson, David, Pačes, Václav, Ansorge, Wilhelm, Kožich, Viktor
• Format: Article
• Language: English
• Subjects: Alternative Splicing - genetics; Alu Elements - genetics; Base Sequence; Binding Sites - genetics; Biological and medical sciences; Cloning, Molecular; Cystathionine beta-Synthase - genetics; European Continental Ancestry Group; Exons - genetics; Fundamental and applied biological sciences. Psychology; Genes. Genome; Humans; Minisatellite Repeats - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Polymorphism, Genetic - genetics; Promoter Regions, Genetic - genetics; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Transcription Factors - genetics
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1998.5437

Cystathionine β-synthase [CBS;l-serine hydro-lyase (adding homocysteine), EC 4.2.1.22] catalyzes the first committed step of transsulfuration and is the enzyme deficient in classical homocystinuria. In this report, we describe the molecular cloning and the complete nucleotide sequence of the human CBS gene. We report a total of 28,046 nucleotides of sequence, which, in addition to the CBS gene, contains ∼5 kb of the 5′ flanking region. The human CBS gene contains 23 exons ranging 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 alternatively used promoter regions that are GC rich (∼80%) and contain 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 ofAlurepeats, which may predispose this gene to deleterious rearrangements. Additionally, we report on a number of DNA sequence repeats that are polymorphic in North American and European Caucasians.