Detection of Copy Number Variation by SNP-Allelotyping

Abstract

Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by an abnormal copy number variation (CNV) with a trisomy of chromosome 17p12. The increase of the DNA-segment copy number is expected to alter the allele frequency of single nucleotide polymorphism (SNP) within the duplicated region. We tested whether SNP allele frequency determined by a Sequenom MassArray can be used to detect the CMT1A mutation. Our results revealed distinct patterns of SNP allele frequency distribution, which reliably differentiated CMT1A patients from controls. This finding suggests that this technique may serve as an alternative approach to identifying CNV in certain diseases, including CMT1A.

Keywords::

• Charcot-Marie-Tooth disease type-1A
• copy number variation
• peripheral myelin protein-22
• single nucleotide polymorphism

Acknowledgement

Authors would like to thank Dr. Trey Langley for providing valuable information about multiple PCR technique, and also wish to thank the technical assistance from Ms. Audra Hamilton, Ms. Sezgi Arpag, Ms. Chelsea Bacon and Vanderbilt Technologies for Advanced Genomics (VANTAGE) core.

Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This study is, in part, supported by grants from NINDS (NS066927 and NS081364), the National Center for Advancing Translational Sciences (CTSA award UL1TR000445) to J.L. and NINDS/ORD 5U54NS065712 to M.E.S.

Supplementary material available online

Supplementary Table 1.