Evidence map›Paper›PMID 29566674›Full record

ArticleBMC genetics2018

A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.

Frédéric Ancot, Philippe Lemay, Susan P Knowler, Karen Kennedy, Sandra Griffiths, Giunio Bruto Cherubini, Jane Sykes, Paul J J Mandigers, Guy A Rouleau, Clare Rusbridge and 1 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 32 citations in OpenAlex.

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  11. An initial genome-wide investigation of protein-losing enteropathy in Gordon setters: Exploratory observations.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2021
    Article
  12. A Deletion inGenes · 2020
    Article
  13. Chiari malformation type I: what information from the genetics?Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2019
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 3 countries.

Frédéric AncotDepartment of Neurosciences, CHU Sainte Justine Research Center, University of Montréal, 3175 Cote-Sainte-Catherine, Room 3.17.006, Montreal, QC, H3T 1C5, Canada.
Philippe LemayDepartment of Neurosciences, CHU Sainte Justine Research Center, University of Montréal, 3175 Cote-Sainte-Catherine, Room 3.17.006, Montreal, QC, H3T 1C5, Canada.
Susan P KnowlerSchool of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7AL, UK.
Karen KennedyDepartment of Medical Imaging, London Health Sciences Centre, London, ON, N6A 5A5, Canada.
Sandra GriffithsStone Lion Veterinary Hospital, 42 High Street, Wimbledon, SW19 5AU, UK.
Giunio Bruto CherubiniDick White Referrals, Six Mile Bottom, Cambridgeshire, CB8 0UH, UK.
Jane SykesThames Valley Veterinary Services, London, ON, N6A 4V2, Canada.
Paul J J MandigersDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584, CM, The Netherlands.
Guy A RouleauMontreal Neurological Institute and McGill University, Montreal, QC, H3A 2B4, Canada.
Clare RusbridgeSchool of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7AL, UK.
Zoha KibarDepartment of Neurosciences, CHU Sainte Justine Research Center, University of Montréal, 3175 Cote-Sainte-Catherine, Room 3.17.006, Montreal, QC, H3T 1C5, Canada. zoha.kibar@recherche-ste-justine.qc.ca.ORCID 0000-0002-6743-049X
Centre Hospitalier Universitaire Sainte-Justine · CAUniversity of Surrey · GBLondon Health Sciences Centre · CAMontreal Neurological Institute and Hospital · CAThames Valley Children's Centre · CAUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSyringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance.

resultsWe identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development.

conclusionsWe identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.

Indexed as

Genetic LociAnimalsArnold-Chiari MalformationCranial Fossa, PosteriorDog DiseasesDogsGenome-Wide Association StudyHaplotypesMagnetic Resonance ImagingPainPolymorphism, Single NucleotideSyringomyeliaChiari malformationCKCS dog breedCranial MRI measurementsSyringomyeliaWhole genome association study

Identifiers

PMID29566674
PMCPMC5865342
OpenAlexW2804862207

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.