Haplotyping of wild type and I278T alleles of the human cystathionine beta-synthase gene based on a cluster of novel SNPs in IVS12.
Haplotyping of wild type and I278T alleles of the human cystathionine beta-synthase gene based on a cluster of novel SNPs in IVS12.
复制标题
DOI：
10.1002/humu.36
复制
发表时间：
2001-04-01
期刊：
影响因子：
3.9
通讯作者：
Koch, H G
中科院分区：
文献类型：
--
作者：
Linnebank, M;Homberger, A;Koch, H G
同型胱氨酸尿症最常见的原因是胱硫醚β-合酶（CBS）缺乏。我们发现IVS 12是CBS基因的一个多态热点，并报道了5个新的单核苷酸多态性（SNP）：g.13514G>A，g.13617A>G，g.13715C>T，g.13800G>A和g.13904C>T。分析50个未受影响的和无关的德国血统的受试者的对照DNA样本，观察到的杂合性频率分别为0.02，0.36，0.18，0.36，和0.36，分别。这些多态性标记组合成四种不同的IVS 12单倍型A1、A2、B1和B2，频率分别为0.75、0.01、0.15和0.09，观察到的总杂合性频率为0.38。该单倍型系统和SNP c.699用于分析受最普遍的CBS突变c.833T>C（外显子8; I278 T）影响的10个等位基因。我们发现，I278 T等位基因分离，至少有两个不同的单倍型，其特征在于上游和下游的多态性位点，而不是共享一个共同的祖先单倍型。即使在种族背景非常相似的患者中，这也是一个显著的发现。新的单倍型系统可能有助于未来CBS基因进化的研究，并可能适合于受同型胱氨酸尿症影响的家族的基因分型。
Homocystinuria is most frequently due to deficiency of cystathionine beta-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.