Kringen Marianne K, Stormo Camilla, Grimholt Runa M, Berg Jens P, Piehler Armin P
Department of Pharmacology, Oslo University Hospital, Ullevål, Oslo, Norway.
BMC Res Notes. 2012 Aug 9;5:425. doi: 10.1186/1756-0500-5-425.
The ATP-binding cassette transporter ABCC6 gene is located on chromosome 16 between its two pseudogenes (ABCC6P1 and ABCC6P2). Previously, we have shown that ABCC6P1 is transcribed and affects ABCC6 at the transcriptional level. In this study we aimed to determine copy number variations of ABCC6, ABCC6P1 and ABCC6P2 in different populations. Moreover, we sought to study the transcription pattern of ABCC6 and ABCC6 pseudogenes in 39 different human tissues.
Genomic DNA from healthy individuals from five populations, Chinese (n = 24), Middle East (n = 20), Mexicans (n = 24), Caucasians (n = 50) and Africans (n = 24), were examined for copy number variations of ABCC6 and its pseudogenes by pyrosequencing and quantitative PCR. Copy number variation of ABCC6 was very rare (2/142; 1.4%). However, one or three copies of ABCC6P1 were relatively common (3% and 8%, respectively). Only one person had a single copy of ABCC6P2 while none had three copies. In Chinese, deletions or duplications of ABCC6P1 were more frequent than in any other population (9/24; 37.5%). The transcription pattern of ABCC6P2 was highly similar to ABCC6 and ABCC6P1, with highest transcription in liver and kidney. Interestingly, the total transcription level of pseudogenes, ABCC6P1 + ABCC6P2, was higher than ABCC6 in most tissues, including liver and kidney.
Copy number variations of the ABCC6 pseudogenes are quite common, especially in populations of Chinese ancestry. The expression pattern of ABCC6P2 in 39 human tissues was highly similar to that of ABCC6 and ABCC6P1 suggesting similar regulatory mechanisms for ABCC6 and its pseudogenes.
ATP结合盒转运蛋白ABCC6基因位于16号染色体上，介于其两个假基因（ABCC6P1和ABCC6P2）之间。此前，我们已表明ABCC6P1可转录并在转录水平上影响ABCC6。在本研究中，我们旨在确定不同人群中ABCC6、ABCC6P1和ABCC6P2的拷贝数变异情况。此外，我们试图研究ABCC6及其假基因在39种不同人体组织中的转录模式。
通过焦磷酸测序和定量PCR检测了来自五个群体（中国人（n = 24）、中东人（n = 20）、墨西哥人（n = 24）、白种人（n = 50）和非洲人（n = 24））健康个体的基因组DNA中ABCC6及其假基因的拷贝数变异。ABCC6的拷贝数变异非常罕见（2/142；1.4%）。然而，ABCC6P1的一个或三个拷贝相对较为常见（分别为3%和8%）。只有一人有ABCC6P2的单拷贝，而无人有三个拷贝。在中国人群中，ABCC6P1的缺失或重复比其他任何群体都更频繁（9/24；37.5%）。ABCC6P2的转录模式与ABCC6和ABCC6P1高度相似，在肝脏和肾脏中的转录水平最高。有趣的是，在包括肝脏和肾脏在内的大多数组织中，假基因ABCC6P1 + ABCC6P2的总转录水平高于ABCC6。
ABCC6假基因的拷贝数变异相当常见，尤其是在有中国血统的人群中。ABCC6P2在39种人体组织中的表达模式与ABCC6和ABCC6P1高度相似，表明ABCC6及其假基因具有相似的调控机制。
