Genetic mapping of distal femoral, stifle, and tibial radiographic morphology in dogs with cranial cruciate ligament disease.
Animals
Anterior Cruciate Ligament
/ diagnostic imaging
Body Size
/ genetics
Chromosome Mapping
Coenzyme A Ligases
/ genetics
Dog Diseases
/ diagnostic imaging
Dogs
Femur
/ diagnostic imaging
Genome-Wide Association Study
Genotype
Growth Hormone
/ genetics
Insulin Receptor Substrate Proteins
/ genetics
Joint Diseases
/ genetics
Myosin Heavy Chains
/ genetics
Osteoarthritis
/ genetics
Repressor Proteins
/ genetics
Tibia
/ diagnostic imaging
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
22
12
2018
accepted:
14
09
2019
entrez:
18
10
2019
pubmed:
18
10
2019
medline:
14
3
2020
Statut:
epublish
Résumé
Cranial cruciate ligament disease (CCLD) is a complex trait. Ten measurements were made on orthogonal distal pelvic limb radiographs of 161 pure and mixed breed dogs with, and 55 without, cranial cruciate partial or complete ligament rupture. Dogs with CCLD had significantly smaller infrapatellar fat pad width, higher average tibial plateau angle, and were heavier than control dogs. The first PC weightings captured the overall size of the dog's stifle and PC2 weightings reflected an increasing tibial plateau angle coupled with a smaller fat pad width. Of these dogs, 175 were genotyped, and 144,509 polymorphisms were used in a genome-wide association study with both a mixed linear and a multi-locus model. For both models, significant (pgenome <3.46×10-7 for the mixed and< 6.9x10-8 for the multilocus model) associations were found for PC1, tibial diaphyseal length and width, fat pad base length, and femoral and tibial condyle width at LCORL, a known body size-regulating locus. Other body size loci with significant associations were growth hormone 1 (GH1), which was associated with the length of the fat pad base and the width of the tibial diaphysis, and a region on CFAX near IRS4 and ACSL4 in the multilocus model. The tibial plateau angle was associated significantly with a locus on CFA10 in the linear mixed model with nearest candidate genes BET1 and MYH9 and on CFA08 near candidate genes WDHD1 and GCH1. MYH9 has a major role in osteoclastogenesis. Our study indicated that tibial plateau slope is associated with CCLD and a compressed infrapatellar fat pad, a surrogate for stifle osteoarthritis. Because of the association between tibial plateau slope and CCLD, and pending independent validation, these candidate genes for tibial plateau slope may be tested in breeds susceptible to CCLD before they develop disease or are bred.
Identifiants
pubmed: 31622367
doi: 10.1371/journal.pone.0223094
pii: PONE-D-18-36665
pmc: PMC6797204
doi:
Substances chimiques
Insulin Receptor Substrate Proteins
0
Repressor Proteins
0
Growth Hormone
9002-72-6
Myosin Heavy Chains
EC 3.6.4.1
Coenzyme A Ligases
EC 6.2.1.-
long-chain-fatty-acid-CoA ligase
EC 6.2.1.3
Banques de données
Dryad
['10.5061/dryad.266k4']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0223094Subventions
Organisme : NIAMS NIH HHS
ID : R21 AR055228
Pays : United States
Organisme : NIGMS NIH HHS
ID : R24 GM082910
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
PLoS Genet. 2011 Oct;7(10):e1002316
pubmed: 22022279
Canine Genet Epidemiol. 2017 Mar 24;4:4
pubmed: 28352471
J Small Anim Pract. 2011 Jul;52(7):347-52
pubmed: 21651558
Stem Cells Dev. 2016 Dec 1;25(23):1808-1817
pubmed: 27733096
Physiol Genomics. 2018 Dec 1;50(12):1051-1058
pubmed: 30265593
J Biol Chem. 1999 Oct 29;274(44):31179-84
pubmed: 10531310
Dev Biol. 2014 Jan 1;385(1):67-82
pubmed: 24161523
Hum Mutat. 2003 Apr;21(4):424-40
pubmed: 12655557
J Am Vet Med Assoc. 2002 Nov 15;221(10):1426-9
pubmed: 12458611
BMC Genet. 2013 Jun 01;14:46
pubmed: 23725562
Vet Surg. 2015 Aug;44(6):777-83
pubmed: 26118493
Anim Genet. 2014 Aug;45(4):542-9
pubmed: 24835129
Biomaterials. 2019 Jun;206:87-100
pubmed: 30927715
Vet Surg. 2009 Jun;38(4):481-9
pubmed: 19538670
Hum Mutat. 2014 Feb;35(2):236-47
pubmed: 24186861
Int J Oncol. 2016 Jul;49(1):51-8
pubmed: 27176124
Sci Signal. 2011 Sep 6;4(189):rs8
pubmed: 21900206
Vet Comp Orthop Traumatol. 2017 May 22;30(3):178-183
pubmed: 28331933
Vet Surg. 2018 Nov;47(8):1009-1015
pubmed: 30303540
BMC Vet Res. 2017 Aug 14;13(1):235
pubmed: 28806971
Arthritis Res Ther. 2015 Nov 10;17:318
pubmed: 26555322
J Am Vet Med Assoc. 2006 Jan 1;228(1):61-4
pubmed: 16426167
Int Immunopharmacol. 2018 Jul;60:41-49
pubmed: 29702282
Am J Vet Res. 2009 Aug;70(8):1013-7
pubmed: 19645583
J Am Vet Med Assoc. 2001 Feb 1;218(3):363-6
pubmed: 11201561
Physiol Genomics. 2018 Jul 1;50(7):523-531
pubmed: 29676954
Nat Genet. 2012 Jun 17;44(7):821-4
pubmed: 22706312
J Am Vet Med Assoc. 2014 Feb 1;244(3):328-38
pubmed: 24432965
Anim Genet. 2007 Dec;38(6):634-8
pubmed: 17931399
Science. 2007 Apr 6;316(5821):112-5
pubmed: 17412960
J Am Vet Med Assoc. 2008 Jun 15;232(12):1818-24
pubmed: 18598150
Connect Tissue Res. 2014 Aug;55(4):275-81
pubmed: 24684544
Vet Surg. 2003 Jul-Aug;32(4):385-9
pubmed: 12866002
J Vet Sci. 2018 Sep 30;19(5):699-707
pubmed: 29929359
J Dairy Sci. 2010 Dec;93(12):5959-69
pubmed: 21094770
Clin Imaging. 2018 Jul - Aug;50:20-30
pubmed: 29253746
Biomed Res Int. 2019 Mar 31;2019:6390182
pubmed: 31049352
BMC Vet Res. 2018 May 16;14(1):161
pubmed: 29769086
J Vet Med Sci. 2006 Jul;68(7):675-9
pubmed: 16891779
PLoS One. 2017 Apr 5;12(4):e0173810
pubmed: 28379989
BMC Genet. 2018 Jun 26;19(1):39
pubmed: 29940858
Vet Surg. 2011 Oct;40(7):830-8
pubmed: 21906096
PLoS Genet. 2016 Feb 01;12(2):e1005767
pubmed: 26828793
Nature. 2010 Oct 14;467(7317):832-8
pubmed: 20881960
PLoS One. 2017 Jun 14;12(6):e0176932
pubmed: 28614352
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Nat Commun. 2016 Jan 22;7:10460
pubmed: 26795439
Vet J. 2017 Jul;225:35-41
pubmed: 28720297
J Am Vet Med Assoc. 2018 Sep 1;253(5):586-597
pubmed: 30110219
J Am Vet Med Assoc. 1999 Sep 15;215(6):811-4
pubmed: 10496133
Growth Horm IGF Res. 2016 Apr;27:7-17
pubmed: 26843472
Vet Surg. 2015 Jan;44(1):46-9
pubmed: 24902869
J Small Anim Pract. 2012 May;53(5):273-7
pubmed: 22489873
Scoliosis Spinal Disord. 2016 Apr 01;11:5
pubmed: 27299157
J Biol Chem. 2009 May 1;284(18):12266-75
pubmed: 19269977
Physiol Genomics. 2010 Oct;42A(2):79-88
pubmed: 20647382
PLoS Biol. 2010 Aug 10;8(8):e1000451
pubmed: 20711490
Mol Genet Genomics. 2017 Aug;292(4):789-794
pubmed: 28342042
PLoS Genet. 2017 Mar 3;13(3):e1006661
pubmed: 28257443
Canine Genet Epidemiol. 2017 Feb 2;4:2
pubmed: 28168039
J Am Vet Med Assoc. 1993 Oct 1;203(7):1016-9
pubmed: 8226247
J Am Vet Med Assoc. 2005 Nov 15;227(10):1604-7
pubmed: 16313037
Front Genet. 2018 Jun 22;9:217
pubmed: 29988410