title: The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms.
abstract: Cystathionine beta-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 approximately 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 (approximately 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 of Alu repeats, 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.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80262, USA. JAN.KRAUS@UCHSC.edu
authors.forename: J P
authors.initials: JP
authors.lastname: Kraus
authors.forename: J
authors.initials: J
authors.lastname: Oliveriusová
authors.forename: J
authors.initials: J
authors.lastname: Sokolová
authors.forename: E
authors.initials: E
authors.lastname: Kraus
authors.forename: C
authors.initials: C
authors.lastname: Vlcek
authors.forename: R
authors.initials: R
authors.lastname: de Franchis
authors.forename: K N
authors.initials: KN
authors.lastname: Maclean
authors.forename: L
authors.initials: L
authors.lastname: Bao
authors.lastname: Bukovsk
authors.forename: D
authors.initials: D
authors.lastname: Patterson
authors.forename: V
authors.initials: V
authors.lastname: Paces
authors.forename: W
authors.initials: W
authors.lastname: Ansorge
authors.forename: V
authors.initials: V
authors.lastname: Kozich
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D020087:Alu Elements / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics; D044465:White People
chemical_list: D014157:Transcription Factors; D003541:Cystathionine beta-Synthase