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K.L. Parker Gaddis 1 and J.B. Cole 2,* 1 Department of Animal Sciences 2 Animal Genomics and Improvement University of Florida Laboratory Gainesville,

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Presentation on theme: "K.L. Parker Gaddis 1 and J.B. Cole 2,* 1 Department of Animal Sciences 2 Animal Genomics and Improvement University of Florida Laboratory Gainesville,"— Presentation transcript:

1 K.L. Parker Gaddis 1 and J.B. Cole 2,* 1 Department of Animal Sciences 2 Animal Genomics and Improvement University of Florida Laboratory Gainesville, FL 32611-0920 Agricultural Research Service, USDA kristen.parkergaddis@ars.usda.gov Beltsville, MD 20705-2350 john.cole@ars.usda.gov Genome-wide association study of fertility traits in dairy cattle using high-density single nucleotide polymorphism marker panels

2 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (2) Introduction Increased production associated with decreased fertility Decreased fertility associated with increased culling Expensive problem to manage Each lost pregnancy costs ~$550 (De Vries 2006)

3 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (3) Materials & Methods Traits: Daughter pregnancy rate (DPR) Heifer conception rate (HCR) Cow conception rate (CCR) Trivariate analysis (e.g., VanRaden et al., 2014) Deregressed PTA from National Dairy Database

4 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (4) Materials & Methods SNP chips Illumina Bovine SNP50 BeadChip (50K) BovineHD Genotyping BeadChip (HD) After editing 60,671 markers included in 50K analysis 312,614 markers included in HD analysis Populations (n = 25,000) Cows only Bulls only Bulls and cows

5 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (5) Materials & Methods GWAS GEMMA version 0.94 (GWAS) Enrichment analyses SNP assigned to closest gene with 25 kbp on the UMD3.1 assembly GO (GOstats) & DAVID, MeSH (meshr) Conducted in R version 3.2.1 Cytoscape (version 3.2.1) Enrichment Map (version 2.0.1)

6 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (6) Results – Bull GWAS CCR – 50K

7 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (7) Results – Bull GWAS CCR – HD HD analysis able to pick up peaks that were not identified with the 50K chip

8 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (8) Results – Bull GWAS Genes significant in HD GWAS and previous studies CCR BTA22APPL1Adaptor protein, phosphotyrosine interaction, PH domain & leucine zipper containing 1 DPR BTA3PER2Period-circadian clock 2 HCR BTA3PER2Period-circadian clock 2 BTA11LTBP1Latent transforming growth factor beta binding protein TRIVARIATE BTA1ITGB5Integrin, beta 5 BTA2CALCRLCalcitonin receptor-like

9 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (9) Results – Cow GWAS CCR – HD

10 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (10) Results – Cow GWAS TRIVARIATE BTA1ST6GAL1ST6 beta-galactosamide alpha-2,6-sialyltransferase 1 BTA2FN1fibronectin 1 BTA5ATP5G2ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C2 (subunit 9) BTA6GCgroup-specific component (vitamin D binding protein) BTA16NR5A2nuclear receptor subfamily 5, group A, member 2 BTA17LIFleukemia inhibitory factor BTA17OSMoncostatin M BTA17KDM2Blysine (K)-specific demethylase 2B BTA18CEACAM1carcinoembryonic antigen-related cell adhesion molecule 1 BTA18HPNhepsin BTA23CLIC5chloride intracellular channel 5 BTA28VDAC2voltage-dependent anion channel 2 BTA29CDKN1Ccyclin-dependent kinase inhibitor 1C (p57, Kip2)

11 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (11) Results – Bull & Cow GWAS CCR – HD The combined population GWAS also showed peaks that were not identified with only cows or only bulls

12 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (12) Results – New QTL from Cow & Bull GWAS CCR BTA10PDE8BPhosphodiesterase 8B ……… ……… ……… ……… ……… ……… ……… ……… ……… ……… ………

13 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (13) Results – Consistent signals across traits DPR – HD

14 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (14) Results – Consistent signals across traits HCR – HD

15 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (15) Results – Consistent signals across traits Trivariate – HD

16 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (16) Gene Ontology Enrichment Gene ontology (GO) enrichment analysis attempts to identify biological functions shared by a group of genes (Ashburner et al., 2000) Genes of interest (P < 0.05 in the GWAS) compared against a background set (all annotated genes within 25 kb of a SNP) GO enrichment analysis performed using DAVID (Huang et al., 2009a, b)

17 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (17) GO Results - Bulls Positive regulation of acrosome reaction (GO:2000344) Nervous system development (GO:0007399) Embryonic placenta development (GO:001892) Embryonic heart tube development (GO:0035050) Developmental maturation (GO:0021700)

18 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (18) GO Results – Bulls & Cows Positive regulation of acrosome reaction (GO:2000344) Ovarian follicle development (GO:0001541) Mating behavior (GO:0007617) Ovulation cycle (GO:0042698) Activation of meiosis involved in egg activation (GO:0060466)

19 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (19) Common GO Network Networks identified in both bull and cow analyses

20 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (20) Results GO enrichment map – bulls compared to cows Networks identified in only bull analyses (Bulls, HD, trivariate) Networks identified in only cow analyses (Cows, HD, CCR)

21 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (21) MeSH Term Enrichment Medical subject headings (MeSH) vocabulary associates terms with articles in MEDLINE that are then mapped to genes (e.g., Morota et al., 2015) Genes of interest (P > 0.05 in the GWAS) compared against a background set (all annotated genes within 25 kb of a SNP) MeSH enrichment analysis performed using meshr (Tsuyuzaki et al., 2015)

22 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (22) Results MeSH – Cows, DPR, Phenomena & Processes

23 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (23) Results MeSH – Bulls, CCR, Anatomy

24 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (24) Discussion 50K QTL also identified using HD data Different QTL identified using different training sets (e.g., bull vs. cow) Multivariate results consistent with univariate analyses GO and MeSH enrichment analyses confirm that GWAS correctly identifying genes associated with fertility

25 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (25) Conclusions Key processes involved in fertility include Oocyte maturation and development Ovulation, mating behavior, and fertilization Embryonic development How do we include networks in selection programs? Selection for functional units rather than single genes

26 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (26) Acknowledgments The Council on Dairy Cattle Breeding (Bowie, MD) provided data used in this study under USDA Nonfunded Cooperative Agreement 58-1245-3-228N. This research was supported by: USDA-NIFA AFRI Grant No. 2013-68004-20365, “Improving Fertility of Dairy Cattle Using Translational Genomics” USDA-ARS project 1265-31000-101-05, “Improving Genetic Predictions in Dairy Animals Using Phenotypic and Genomic Information”

27 Parker Gaddis and Cole 2015 ADSA-ASAS Joint Annual Meeting, Orlando, FL, July 14, 2015 (27) Questions? http://gigaom.com/2012/05/31/t-mobile-pits-its-math-against-verizons-the-loser-common-sense/shutterstock_76826245/

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