Quantitative trait loci (QTL) study identifies novel genomic regions associated to Chiari-Like Malformation in Griffon Bruxellois dogs
Philipe Lemay,1 Susan P. Knowler,2 Samir Bouasker,1 Yohann Nédélec,1 Simon Platt,3 Courtenay Freeman,3 Georgina Child,4 Luis B. Barreiro,1 Guy A. Rouleau,5 Clare Rusbridge 2,6 and Zoha Kibar1,
1CHU Sainte Justine Research Center and University of Montréal, 2 Fitzpatrick Referrals, Halfway Lane, Eashing, Godalming, Surrey, GU7 2QQ, 3 Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, 4 Small Animal Specialist Hospital, 1 Richardson Place North Ryde NSW 2113, Australia, 5 Montreal Neurological Institute and McGill University 6 School of Veterinary Medicine, Faculty of Health & Medical Sciences, Surrey, UK
We are excited and delighted to announce after four years hard work collecting DNA from Griffon Bruxellois from dedicated owners and worldwide, the genetics group headed by Dr Zoha Kibar at Sainte Justine Hospital Research Center and University of Montreal identified two DNA regions that were strongly associated with Chiari-like malformation in the dog. They used a quantitative trait locus (QTL) approach that linked DNA molecular markers with magnetic resonance imaging information gleaned by researcher Penny Knowler and neurologist Dr Clare Rusbridge (see here) This identified two novel genomic regions involved in development of the skull and has been associated with a disease linked to Chiari malformation in humans. The team is very excited by this finding because not only may it help dogs and breeders but it might help understand the condition in humans.
The research was published in the journal PLOS ONE: http://dx.plos.org/10.1371/journal.pone.0089816
To investigate the genetic complexity of the disease, a total of 14 quantitative skull and atlas measurements were taken and were tested for association to CM. Seven traits were found to be associated to CM and were subjected to a whole-genome association study. One of the two genomic region identified contains an excellent candidate gene called Sall-1 since its equivalent in humans is is mutated in Townes-Brocks syndrome which has previously been associated to CMI. The dog model is the only known naturally-occurring animal model for CMI in humans. Hence, gene identification studies in CM in the dog might provide an entry point for identification of novel genes and pathways involved in the pathogenesis of CMI in humans.
See the changes in the shape of the Griffon head with SM -here (u-tube looks blank at start)