Marco Groth and Karol Szafranski contributed equally to this work.
High-resolution mapping of the 8p23.1 beta-defensin cluster reveals strictly concordant copy number variation of all genes†
Article first published online: 9 MAY 2008
© 2008 Wiley-Liss, Inc.
Volume 29, Issue 10, pages 1247–1254, October 2008
How to Cite
Groth, M., Szafranski, K., Taudien, S., Huse, K., Mueller, O., Rosenstiel, P., Nygren, A. O.H., Schreiber, S., Birkenmeier, G. and Platzer, M. (2008), High-resolution mapping of the 8p23.1 beta-defensin cluster reveals strictly concordant copy number variation of all genes. Hum. Mutat., 29: 1247–1254. doi: 10.1002/humu.20751
Communicated by Graham Taylor
- Issue published online: 23 SEP 2008
- Article first published online: 9 MAY 2008
- Manuscript Accepted: 14 JAN 2008
- Manuscript Received: 17 OCT 2007
- Wilhelm Sander Stiftung. Grant Number: 2005.045.1
- Bundesministerium für Bildung und Forschung. Grant Numbers: 0313652D, 01GS0426, 01GR0504
- Deutsche Forschungsgemeinschaft. Grant Numbers: Hu 498/3-1, SFB617
- copy number variation;
- multiplex ligation-dependent probe amplification;
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 0,1–8, 2008. © 2008 Wiley-Liss, Inc.