Experimental validation of in silico predicted KCNA1, KCNA2, KCNA6 and KCNQ2 genes for association studies of peripheral nerve hyperexcitability syndrome in Jack Russell Terriers

Van Poucke, Mario; Vanhaesebrouck, An E.; Peelman, Luc J.; Van Ham, Luc

doi:10.1016/j.nmd.2012.01.008

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Volume 22, Issue 6 , Pages 558-565, June 2012

Experimental validation of in silico predicted KCNA1, KCNA2, KCNA6 and KCNQ2 genes for association studies of peripheral nerve hyperexcitability syndrome in Jack Russell Terriers

Mario Van Poucke
- Department of Nutrition, Genetics, and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- Corresponding author. Address: Laboratory for Animal Genetics, Heidestraat 19, B-9820 Merelbeke, Belgium. Tel.: +32 9 2647806; fax: +32 9 2647849.
- They contributed equally to this work.
An E. Vanhaesebrouck
- Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- Queen’s Veterinary School Hospital, Cambridge University, CB3 0ES, UK
- They contributed equally to this work.
Luc J. Peelman
- Department of Nutrition, Genetics, and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Luc Van Ham
- Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium

Received 22 August 2011; received in revised form 9 January 2012; accepted 16 January 2012. published online 16 February 2012.

Abstract

KCNA1, KCNA2, KCNA6 and KCNQ2 are associated with peripheral nerve hyperexcitability in humans. In order to determine if these genes are also involved in Jack Russell Terriers with a similar syndrome characterized by myokymia and neuromyotonia, their predicted canine orthologs were first validated experimentally. They were found either incompletely or even incorrectly annotated, mainly due to gaps in the canine genomic sequence and insufficient transcript data. Canine KCNQ2 was found to contain 20 coding exons, of which three are not described in humans. It encodes for at least 14 different transcript variants in the frontal cortex of a single dog, of which only four are also described in humans. Mutation detection in Jack Russell Terriers diagnosed with peripheral nerve hyperexcitability revealed no pathogenetic relevant structural mutations. However, the four missense sequence variations and the 14 transcript variants of KCNQ2 will contribute to the study of the functional diversity of voltage-gated potassium channels.

Keywords: Gene prediction error, Myokymia, Neuromyotonia, Transcript variant, Voltage-gated potassium channel