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

Kraus, Jan P.; Oliveriusová, Jana; Sokolová, Jitka; Kraus, Eva; Vlček, Čestmı ́r; Franchis, R. de; Maclean, Kenneth N.; Bao, Liming; Bukovská, Gabriela; Patterson, David; Pačes, Václav; Ansorge, Wilhelm; Kožich, Viktor

doi:10.1006/geno.1998.5437

Cited by 125 publications

(114 citation statements)

References 32 publications

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“…39 The human cystathionine betasynthase gene uses multiple transcription initiation sites to yield at least five mRNA isoforms differing at their 5′ ends. 40 The original protein of A. flavus cystathionine beta-synthase was composed of four exons but the AS protein had only two exons with alternative 5′ sites (Supplementary Figure 1). Peptide TRTSDLPSTLQPHEQK (spectrum see Supplementary Figure 1) confirmed the boundaries and linkup of the two exons for the AS protein, where peptides AIVAGAGTGGTITGLSR and DYN-FGKDDVVVVILPDSIR showed the original protein used different splice sites and translation activity occurred in the intron of the AS protein.…”

Section: Resultsmentioning

confidence: 99%

Detection of Alternative Splice Variants at the Proteome Level in Aspergillus flavus

et al. 2010

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Identification of proteins from proteolytic peptides or intact proteins plays an essential role in proteomics. Researchers use search engines to match the acquired peptide sequences to the target proteins. However, search engines depend on protein databases to provide candidates for consideration. Alternative splicing (AS), the mechanism where the exon of pre-mRNAs can be spliced and rearranged to generate distinct mRNA and therefore protein variants, enable higher eukaryotic organisms, with only a limited number of genes, to have the requisite complexity and diversity at the proteome level. Multiple alternative isoforms from one gene often share common segments of sequences. However, many protein databases only include a limited number of isoforms to keep minimal redundancy. As a result, the database search might not identify a target protein even with high quality tandem MS data and accurate intact precursor ion mass. We computationally predicted an exhaustive list of putative isoforms of Aspergillus flavus proteins from 20 371 expressed sequence tags to investigate whether an alternative splicing protein database can assign a greater proportion of mass spectrometry data. The newly constructed AS database provided 9807 new alternatively spliced variants in addition to 12 832 previously annotated proteins. The searches of the existing tandem MS spectra data set using the AS database identified 29 new proteins encoded by 26 genes. Nine fungal genes appeared to have multiple protein isoforms. In addition to the discovery of splice variants, AS database also showed potential to improve genome annotation. In summary, the introduction of an alternative splicing database helps identify more proteins and unveils more information about a proteome.

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Section: Resultsmentioning

confidence: 99%

Detection of Alternative Splice Variants at the Proteome Level in Aspergillus flavus

et al. 2010

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“…The human CBS gene is located at chromosome 21q22.3 (Munke et al 1988), and it was not too long ago that the entire CBS gene was cloned (Kraus et al 1998). The coding sequence comprises from exon 1 to exon 14 and exon 16.…”

Section: Introductionmentioning

confidence: 99%

“…The 5¢ UTR of the messenger RNA CBS gene is composed of one of the alternatively spliced exons of -1a to -1e in addition to the invariably present exon 0. Exons 16 and 17 comprise 3¢ UTR (Chasse et al 1995;Kraus et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria

Lee

Yoo

et al. 2005

J Hum Genet

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Homocystinuria is an autosomal recessive inborn error of metabolism that is most often caused by mutation in the cystathionine beta-synthase (CBS) gene. Patients may develop serious clinical manifestations such as lens dislocation, mental retardation, osteoporosis, and atherothrombotic vascular disease. Over 100 mutations have been reported, but so far, none have been reported in Korea. Mutation analysis of the CBS gene in six Korean patients with homocystinuria was performed by direct sequencing. Eight mutations were identified, including four known mutations (T257M, R336C, T353M, and G347S) and four novel mutations (L154Q, A155V, del234D, and A288T). All patients were compound heterozygotes. To characterize these mutations, normal or mutated forms of CBS were cloned into pcDNA3.1 expression vector followed by transfection into mammalian cells for transient expression. Whereas the expression levels of mutant proteins were comparable to that of normal control, enzyme activities of all the mutant forms were significantly decreased. In addition, a novel single nucleotide polymorphism, R18C, was identified, which showed onethird to two-thirds the enzyme activity of wild type and 1% of the allele frequency in normal control. The spectrum of mutations observed in Korean patients bears less resemblance to those observed in Western countries.

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“…Moreover, the mutations found in each patient were also analyzed in parental genomic DNA samples. In patients 3, 5 and 6 we examined also four polymorphisms in the CBS gene (c. 699C>T, c.1080C>T, c.1985T>C, and a 31bp VNTR polymorphism in intron 13 as described by Kraus et al, 1998). The alleles carrying novel mutations were cloned into the expression cassettes derived from plasmid pHCS3.…”

Section: Methodsmentioning

confidence: 99%

“…Novel mutations are indicated in bold. 3 Mutations were localized in exons and introns according to a previous report on gene organization (Kraus et al, 1998). All mutations observed in cDNA were verified in genomic DNA samples by sequencing using numbering system as described above and/or by analysis of restriction fragment length polymorphisms (RFLP); -, the mutation abolishes the restriction site; +, the mutation forms a novel site for the indicated restriction endonuclease.…”

Section: Novel Mutation C1039+1g>tmentioning

confidence: 99%

Identification and functional analysis of two novel mutations in the CBS gene in Polish patients with homocystinuria

et al. 2004

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Homocystinuria due to cystathionine β-synthase (CBS) deficiency is an inherited disorder of homocysteine transsulfuration, which manifests by neurological, vascular and connective tissue involvement. So far, 130 pathogenic mutations have been recognized in the CBS gene. We examined 10 independent alleles in Polish patients suffering from CBS deficiency, and we detected four already described mutations (c.1224-2A>C, c.684C>A, c.833T>C, and c.442G>A) and two novel mutations (c.429C>G and c.1039+1G>T). The pathogenicity of the novel mutations was demonstrated by expression in E.coli. This is the first published communication on mutations leading to CBS deficiency in Poland.

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

Cited by 125 publications

References 32 publications

Detection of Alternative Splice Variants at the Proteome Level in Aspergillus flavus

Detection of Alternative Splice Variants at the Proteome Level in Aspergillus flavus

Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria

Identification and functional analysis of two novel mutations in the CBS gene in Polish patients with homocystinuria

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