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Haplotyping of wild type and I278T alleles of the human cystathionine β-synthase gene based on a cluster of novel SNPs in IVS12

  1. Michael Linnebank1,
  2. Anja Homberger1,
  3. Jan Peter Kraus2,
  4. Erik Harms1,
  5. Viktor Kozich3,
  6. Hans Georg Koch1,*

Article first published online: 2 APR 2001

DOI: 10.1002/humu.36

Issue

Human Mutation

Human Mutation

Special Issue: SNP 2000: Third International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis

Volume 17, Issue 4, pages 350–351, April 2001

Additional Information

How to Cite

Linnebank, M., Homberger, A., Kraus, J. P., Harms, E., Kozich, V. and Koch, H. G. (2001), Haplotyping of wild type and I278T alleles of the human cystathionine β-synthase gene based on a cluster of novel SNPs in IVS12 . Hum. Mutat., 17: 350–351. doi: 10.1002/humu.36

Author Information

  1. 1

    Universitaet Muenster, Klinik und Poliklinik für Kinderheilkunde, Germany

  2. 2

    University of Colorado, School of Medicine, Department of Pediatrics, Denver, CO

  3. 3

    Charles University, 1st Faculty of Medicine, Inst. of Inherited Metabolic Disorders, Praha, Czech Republic

*Klinik und Poliklinik für Kinderheilkunde, Albert-Schweitzer-Str. 33, D-48149 Muenster, Germany

  1. Communicated by Mark H. Paalman

  2. Online Citation: Human Mutation, Mutation in Brief #407 (2001) Online http://journals.wiley.com/1059-7794/pdf/mutation/407.pdf

Publication History

  1. Issue published online: 2 APR 2001
  2. Article first published online: 2 APR 2001
  3. Manuscript Accepted: 6 FEB 2001
  4. Manuscript Received: 28 NOV 2000

Funded by

  • Interdisziplinaeres Zentrum fuer Klinische Forschung (IZKF) Muenster. Grant Number: B2
  • the Ministry of Health of the Czech Republic. Grant Number: M/26-3
  • the Fogarty Foundation. Grant Number: R03 TW00989
  • NIH

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Keywords:

  • cystathionine b-synthase;
  • CBS;
  • homocystinuria;
  • haplotype;
  • SNP

Abstract

Homocystinuria is most frequently due to deficiency of cystathionine β-synthase (CBS). We identified IVS12 as a polymorphism hot spot of the human CBS gene and report five novel single nucleotide polymorphisms (SNPs): g.13514G>A, g.13617A>G, g.13715C>T, g.13800G>A, and g.13904C>T. Analyzing 50 control DNA samples of unaffected and unrelated subjects of German origin the observed frequencies of heterozygosity were 0.02, 0.36, 0.18, 0.36, and 0.36, respectively. These polymorphic markers were combined into four distinct IVS12-haplotypes A1, A2, B1, and B2, revealing frequencies of 0.75, 0.01, 0.15, and 0.09, respectively, with an observed overall frequency of heterozygosity at 0.38. This haplotype system and the SNP c.699 were employed in the analysis of ten alleles affected by the most prevalent CBS mutation, c.833T>C (exon 8; I278T). We found that the I278T alleles segregate with at least two distinct haplotypes characterized by upstream and downstream polymorphic sites instead of sharing a common ancestral haplotype. This was a remarkable finding even in patients with very similar ethnic background. The novel haplotype system may facilitate future studies on the evolution of the CBS gene and might be suited for genotyping of families affected by homocystinuria. Hum Mutat 17:350-351, 2001. © 2001 Wiley-Liss, Inc.

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