High-Resolution Mapping of the 8p23.1 Beta-Defensin Cluster Reveals Strictly Concordant Copy Number Variation of All Genes
High-Resolution Mapping of the 8p23.1 Beta-Defensin Cluster Reveals Strictly Concordant Copy Number Variation of All Genes
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DOI：
10.1002/humu.20751
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发表时间：
2008-10-01
期刊：
影响因子：
3.9
通讯作者：
Platzer, Matthias
中科院分区：
文献类型：
--
作者：
Groth, Marco;Szafranski, Karol;Platzer, Matthias
人类基因组的一个意想不到的特征是个体之间的高度结构变异性。通常，基因组的大区域表现出结构多态性，并且许多在其丰度上有所不同。然而，需要准确的方法来表征和分型这种拷贝数变异（CNV）。人类8p23.1区域的防御蛋白簇是研究得最好的CNV区域之一，因为它与先天免疫、炎症和癌症具有潜在的临床相关性。该区域可分为两个亚簇，其中主要含有α -或β -防御素基因。先前评估个体拷贝数的研究给出了不同的结果，关于整个防御蛋白簇是不同的还是只有特定的基因。我们应用多重连接依赖探针扩增（MLPA）技术测量了42个样本的防御蛋白位点拷贝数。数据显示，在每个个体中，β -防御素集群内的所有10个基因座的拷贝数都是严格一致的，而α -防御素集群内的7个基因座在每条染色体上一致地发现了单拷贝。唯一的例外是DEFA3，它位于α -防御蛋白簇内，并且被发现在个体间拷贝数也不同。防御素群的绝对拷贝数从2到9不等，DEFA3群的绝对拷贝数从0到4不等。包括HapMap样本在内的cnv型个体是公开的，可以作为确定绝对拷贝数的通用参考。在此基础上，MLPA是一种可靠的介质检测技术。到8p23.1防御蛋白CNV在不同临床表型关联研究中的高通量分型。植物学报29(10),1247-1254,2008。(c) 2008 Wiley-Liss, Inc。
One unexpected feature of the human genome is the high structural variability across individuals. Frequently, large regions of the genome show structural polymorphisms and many vary in their abundance. However, accurate methods for the characterization and typing of such copy number variations (CNV) are needed. The defensin cluster at the human region 8p23.1 is one of the best studied CNV regions due to its potential clinical relevance for innate immunity, inflammation, and cancer. The region can be divided into two subclusters, which harbor predominantly either alpha- or beta-defensin genes. Previous studies assessing individual copy numbers gave different results regarding whether the complete beta defensin cluster varies or only particular genes therein. We applied multiplex ligation-dependent probe amplification (MLPA) to measure defensin locus copy numbers in 42 samples. The data show strict copy number concordance of all 10 loci typed within the beta-defensin Cluster in each individual, while seven loci within the alpha,defensin cluster are consistently found as single copies per chromosome. The exception is DEFA3, which is located within the alpha-defensin cluster and was found to also differ in copy number interindividually. Absolute copy numbers ranged from two to nine for the beta-defensin cluster and zero to four for DEFA3. The CNV-typed individuals, including HapMap samples, are publicly available and may serve as a universal reference for absolute copy number determination. On this basis, MLPA represents a reliable technique for medium. to high-throughput typing of 8p23.1 defensin CNV in association studies for diverse clinical phenotypes. Hum Mutat 29(10), 1247-1254, 2008. (c) 2008 Wiley-Liss, Inc.