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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
Author(s) -
Linnebank Michael,
Homberger Anja,
Kraus Jan Peter,
Harms Erik,
Kozich Viktor,
Koch Hans Georg
Publication year - 2001
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.36
Subject(s) - haplotype , biology , genetics , cystathionine beta synthase , loss of heterozygosity , single nucleotide polymorphism , genotyping , allele , gene , genotype , microbiology and biotechnology , amino acid , methionine
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.