CYP2D6: novel genomic structures and alleles
CYP2D6: novel genomic structures and alleles
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DOI：
10.1097/fpc.0b013e3283317b95
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发表时间：
2009-10-01
影响因子：
2.6
通讯作者：
Black, John L.
中科院分区：
文献类型：
--
作者：
Kramer, Whitney E.;Walker, Denise L.;Black, John L.
目的CYP 2D 6是一个多态性基因。已观察到其被删除、被复制和经历涉及CYP 2D 7假基因和周围序列的重组事件。本研究的目的是发现干扰临床基因分型平台的CYP 2D 6重组体的基因组结构。方法通过长距离PCR扩增单个基因、PCR片段分析、等位基因特异性引物延伸试验、PCR扩增片段分析结果描述了新的等位基因、基因组结构和这些结构的DNA序列。在50例CYP 2D 6基因重复或倍增的DNA样本中，有49例检测到两个等位基因，而含有重复或倍增的染色体上有相同的串联等位基因。结论发现了几个新的CYP 2D 6等位基因和基因组结构，为CYP 2D 6基因分型提供了依据。研究结果表明，导致CYP 2D 6复制和繁殖的重组事件是由于减数分裂期间染色体间交换以外的机制造成的。药物遗传学和基因组学19：813-822（C）2009年威科健康|利平科特威廉姆斯&威尔金斯。
Objective CYP2D6 is a polymorphic gene. It has been observed to be deleted, to be duplicated and to undergo recombination events involving the CYP2D7 pseudogene and surrounding sequences. The objective of this study was to discover the genomic structure of CYP2D6 recombinants that interfere with clinical genotyping platforms that are available today.Methods Clinical samples containing rare homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals and two different alleles were analyzed by long-range PCR amplification of individual genes, PCR fragment analysis, allele-specific primer extension assay, and DNA sequencing to characterize alleles and genomic structure.Results Novel alleles, genomic structures, and the DNA sequence of these structures are described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene duplications or multiplications where two alleles were detected, the chromosome containing the duplication or multiplication had identical tandem alleles.Conclusion Several new CYP2D6 alleles and genomic structures are described which will be useful for CYP2D6 genotyping. The findings suggest that the recombination events responsible for CYP2D6 duplications and multiplications are because of mechanisms other than interchromosomal crossover during meiosis. Pharmacogenetics and Genomics 19:813-822 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.