Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21818326
TITLE
A non-synonymous mutation in the canine Pkd1 gene is associated with autosomal dominant polycystic kidney disease in Bull Terriers.
ABSTRACT
Polycystic Kidney Disease is an autosomal dominant disease common in some lines of Bull Terriers (BTPKD). The disease is linked to the canine orthologue of human PKD1 gene, Pkd1, located on CFA06, but no disease-associated mutation has been reported. This study sequenced genomic DNA from two Bull Terriers with BTPKD and two without the disease. A non-synonymous G>A transition mutation in exon 29 of Pkd1 was identified. A TaqMan® SNP Genotyping Assay was designed and demonstrated the heterozygous detection of the mutation in 47 Bull Terriers with BTPKD, but not in 102 Bull Terriers over one year of age and without BTPKD. This missense mutation replaces a glutamic acid residue with a lysine residue in the predicted protein, Polycystin 1. This region of Polycystin 1 is highly conserved between species, and is located in the first cytoplasmic loop of the predicted protein structure, close to the PLAT domain and the second transmembrane region. Thus, this change could alter Polycystin 1 binding or localization. Analytic programs PolyPhen 2, Align GVGD and SIFT predict this mutation to be pathogenic. Thus, BTPKD is associated with a missense mutation in Pkd1, and the application of this mutation specific assay could reduce disease transmission by allowing diagnosis of disease in young animals prior to breeding.
DATE PUBLISHED
2011
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/02/15
accepted 2011/06/28
epublish 2011/07/27
entrez 2011/08/06 06:00
pubmed 2011/08/06 06:00
medline 2011/12/13 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gharahkhani P Gharahkhani Puya P School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
O'Leary CA O'Leary Caroline A CA
Kyaw-Tanner M Kyaw-Tanner Myat M
Sturm RA Sturm Richard A RA
Duffy DL Duffy David L DL
INVESTIGATORS
JOURNAL
VOLUME: 6
ISSUE: 7
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2011
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Lab Invest. 1999 Oct;79(10):1311-23 10532593
Cites Cell. 1996 Dec 13;87(6):979-87 8978603
Cites Aust Vet J. 1999 Jun;77(6):361-6 10812399
Cites Eur J Hum Genet. 2000 May;8(5):353-9 10854095
Cites Hum Mol Genet. 2000 Nov 1;9(18):2617-27 11063721
Cites Biochim Biophys Acta. 2000 Dec 15;1535(1):21-35 11113628
Cites Am J Hum Genet. 2001 Jan;68(1):46-63 11115377
Cites Genet Test. 2000;4(4):365-70 11216660
Cites J Clin Invest. 1997 Jan 15;99(2):194-9 9005987
Cites Bioessays. 1997 Feb;19(2):137-45 9046243
Cites Am J Physiol. 1997 Apr;272(4 Pt 2):F451-9 9140045
Cites Nat Genet. 1997 Oct;17(2):179-81 9326937
Cites J Cell Biol. 1998 Jan 12;140(1):211-21 9425168
Cites Annu Rev Cell Dev Biol. 1997;13:119-46 9442870
Cites Vet Pathol. 1998 Jan;35(1):77-81 9545140
Cites Genet Anal. 1999 Feb;14(5-6):143-9 10084106
Cites J Cell Biol. 1999 Mar 8;144(5):1019-31 10085298
Cites Acta Med Scand Suppl. 1957;328:1-255 13469269
Cites J Small Anim Pract. 2004 Nov;45(11):563-7 15553195
Cites Hum Mol Genet. 2004 Dec 15;13(24):3069-77 15496422
Cites J Mol Med (Berl). 2005 Aug;83(8):638-46 15772804
Cites J Am Soc Nephrol. 2007 Jul;18(7):2143-60 17582161
Cites FASEB J. 2007 Dec;21(14):3974-85 17606808
Cites Hum Mutat. 2008 Nov;29(11):1342-54 18951461
Cites Kidney Int. 2009 Apr;75(8):848-55 19165178
Cites Anim Genet. 2009 Aug;40(4):543-6 19397527
Cites J Biol Chem. 2009 Nov 20;284(47):32942-9 19759016
Cites Int J Cancer. 2010 Jul 1;127(1):239-44 19876913
Cites J Am Soc Nephrol. 2001 Apr;12(4):834-45 11274246
Cites Aust Vet J. 2001 Mar;79(3):181-4 11301745
Cites Hum Mol Genet. 2001 Oct 1;10(21):2385-96 11689485
Cites Am J Pathol. 2002 Mar;160(3):973-83 11891195
Cites Kidney Int. 2002 May;61(5):1588-99 11967008
Cites Anim Genet. 2003 Oct;34(5):358-61 14510672
Cites J Am Soc Nephrol. 2004 Oct;15(10):2548-55 15466259
Cites Vet Pathol. 1980 Jul;17(4):436-42 7385577
Cites Nucleic Acids Res. 1988 Feb 11;16(3):1215 3344216
Cites Kidney Int. 1993 Mar;43(3):522-34 8455352
Cites Lancet. 1994 Apr 2;343(8901):824-7 7908078
Cites J Med Genet. 1994 Feb;31(2):115-20 8182715
Cites Mol Biol Cell. 1996 Aug;7(8):1209-24 8856665
Cites Mol Med. 1996 Nov;2(6):702-11 8972485
Cites Mamm Genome. 2000 Feb;11(2):120-30 10656926
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Amino Acid Sequence
Animals
Base Sequence
Computational Biology
DNA Mutational Analysis
Dog Diseases genetics
Dogs genetics
Exons genetics
Genetic Predisposition to Disease genetics
Humans genetics
Mutation genetics
Polycystic Kidney, Autosomal Dominant veterinary
Polymorphism, Single Nucleotide genetics
Sequence Alignment genetics
TRPP Cation Channels genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 TRPP Cation Channels
0 polycystic kidney disease 1 protein
OTHER ID's
OTHERID SOURCE
PMC3144903 NLM