Pamela Xing Yi Soh1, Juliana Maria Marin Cely1, Sally-Anne Mortlock1, Christopher James Jara1, Rachel Booth1, Siria Natera2, Ute Roessner2, Ben Crossett3, Stuart Cordwell1,3, Mehar Singh Khatkar4, Peter Williamson5. 1. School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, Australia. 2. Metabolomics Australia, School of BioSciences, University of Melbourne, Parkville, Australia. 3. Sydney Mass Spectrometry, Charles Perkins Centre, University of Sydney, Sydney, Australia. 4. Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, Australia. 5. School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, Australia. p.williamson@sydney.edu.au.
Abstract
INTRODUCTION: German shepherd dogs (GSDs) are a popular breed affected by numerous disorders. Few studies have explored genetic variations that influence canine blood metabolite levels. OBJECTIVES: To investigate genetic variants affecting the natural metabolite variation in GSDs. METHODS: A total of 82 healthy GSDs were genotyped on the Illumina CanineHD Beadchip, assaying 173,650 markers. For each dog, 74 metabolites were measured through liquid and gas chromatography mass spectrometry (LC-MS and GC-MS) and were used as phenotypes for genome-wide association analyses (GWAS). Sliding window and homozygosity analyses were conducted to fine-map regions of interest, and to identify haplotypes and gene dosage effects. RESULTS: Summary statistics for 74 metabolites in this population of GSDs are reported. Forty-one metabolites had significant associations at a false discovery rate of 0.05. Two associations were located around genes which encode for enzymes for the relevant metabolites: 4-hydroxyproline was significantly associated to D-amino acid oxidase (DAO), and threonine to L-threonine 3-dehydrogenase (LOC477365). Three of the top ten haplotypes associated to 4-hydroxyproline included at least one SNP on DAO. These haplotypes occurred only in dogs with the highest 15 measurements of 4-hydroxyproline, ranging in frequency from 16.67 to 20%. None of the dogs were homozygous for these haplotypes. The top two haplotypes associated to threonine included SNPs on LOC477365 and were also overrepresented in dogs with the highest 15 measurements of threonine. These haplotypes occurred at a frequency of 90%, with 80% of these dogs homozygous for the haplotypes. In dogs with the lowest 15 measurements of threonine, the haplotypes occurred at a frequency of 26.67% and 0% homozygosity. CONCLUSION: DAO and LOC477365 were identified as candidate genes affecting the natural plasma concentration of 4-hydroxyproline and threonine, respectively. Further investigations are needed to validate the effects of the variants on these genes.
INTRODUCTION: German shepherd dogs (GSDs) are a popular breed affected by numerous disorders. Few studies have explored genetic variations that influence canine blood metabolite levels. OBJECTIVES: To investigate genetic variants affecting the natural metabolite variation in GSDs. METHODS: A total of 82 healthy GSDs were genotyped on the Illumina CanineHD Beadchip, assaying 173,650 markers. For each dog, 74 metabolites were measured through liquid and gas chromatography mass spectrometry (LC-MS and GC-MS) and were used as phenotypes for genome-wide association analyses (GWAS). Sliding window and homozygosity analyses were conducted to fine-map regions of interest, and to identify haplotypes and gene dosage effects. RESULTS: Summary statistics for 74 metabolites in this population of GSDs are reported. Forty-one metabolites had significant associations at a false discovery rate of 0.05. Two associations were located around genes which encode for enzymes for the relevant metabolites: 4-hydroxyproline was significantly associated to D-amino acid oxidase (DAO), and threonine to L-threonine 3-dehydrogenase (LOC477365). Three of the top ten haplotypes associated to 4-hydroxyproline included at least one SNP on DAO. These haplotypes occurred only in dogs with the highest 15 measurements of 4-hydroxyproline, ranging in frequency from 16.67 to 20%. None of the dogs were homozygous for these haplotypes. The top two haplotypes associated to threonine included SNPs on LOC477365 and were also overrepresented in dogs with the highest 15 measurements of threonine. These haplotypes occurred at a frequency of 90%, with 80% of these dogs homozygous for the haplotypes. In dogs with the lowest 15 measurements of threonine, the haplotypes occurred at a frequency of 26.67% and 0% homozygosity. CONCLUSION:DAO and LOC477365 were identified as candidate genes affecting the natural plasma concentration of 4-hydroxyproline and threonine, respectively. Further investigations are needed to validate the effects of the variants on these genes.
Authors: David Leander Petersen; Jens Berthelsen; Andreas Willerslev-Olsen; Simon Fredholm; Sally Dabelsteen; Charlotte Menné Bonefeld; Carsten Geisler; Anders Woetmann Journal: Tumour Biol Date: 2017-07
Authors: Amaury Vaysse; Abhirami Ratnakumar; Thomas Derrien; Erik Axelsson; Gerli Rosengren Pielberg; Snaevar Sigurdsson; Tove Fall; Eija H Seppälä; Mark S T Hansen; Cindy T Lawley; Elinor K Karlsson; Danika Bannasch; Carles Vilà; Hannes Lohi; Francis Galibert; Merete Fredholm; Jens Häggström; Ake Hedhammar; Catherine André; Kerstin Lindblad-Toh; Christophe Hitte; Matthew T Webster Journal: PLoS Genet Date: 2011-10-13 Impact factor: 5.917
Authors: Christopher L Campbell; Claude Bhérer; Bernice E Morrow; Adam R Boyko; Adam Auton Journal: G3 (Bethesda) Date: 2016-11-08 Impact factor: 3.154
Authors: Atiyeh Peiravan; Francesca Bertolini; Max F Rothschild; Kenneth W Simpson; Albert E Jergens; Karin Allenspach; Dirk Werling Journal: PLoS One Date: 2018-07-20 Impact factor: 3.240