What will mapping the genome mean to the industry?

1. What will mapping the genome mean to the industry? Clare A. Gill, Ph.D. Department of Animal Science Texas A&M University

2. Outline • Current Status of the Bovine Genome Map • International Bovine BAC Map Consortium • Strategy for Genome Sequencing • Industry Applications

3. 10-30m 30 pairs of chromosomes

4. Bovine Genome 30 pairs of chromosomes 3,000,000,000 base pairs 30,000 - 50,000 genes Genes make up less than 10% of the genome Base changes can affect phenotype

5. Mapping Sequencing Bovine Genome Bioinformatics

6. Genetic Linkage map of bovine chromosome 1 BM6438 TGLA49 INRA117 DIK70 RM95 BM4307 TGLA57 BM1312 BM6506 CSSM32 BL28 MAF46 URBO14

8. http://www.marc.usda.gov/genome/htmls/LinkageMap

11. Grisart et al. (2001) Genome Res. 12: 222-231

13. BAC Fingerprints • http://www.bcgsc.bc.ca/projects/bovine_mapping/ • The current database contains 294,652clones • 45,000 Angus BACs contributed by TAMU • >1000 loci mapped using TAMU library • 280,000 BACs will be end sequenced • 100,000 BAC ends will be contributed by TAMU • Cattle is the only animal species that will have the BAC Map completed prior to genomic sequencing BAC End Sequencing

14. International BAC Map Consortium Members USDA-MARC INRA BCGSC AgResearch TIGR Roslin Institute Baylor College of Medicine CSIRO Texas A&M University University of Alberta plus researchers from University of Illinois Brazil & Japan

16. DNA Markers = Bookmarks Sequence = Words on Page

17. The Bovine Genome Project From Green (2001) Nat. Rev. Genet. 2: 573-583.

18. Bovine Genome Sequencing Initiative • White Paper submitted to NIH • Gibbs, Weinstock, Kappes, Schook, Skow & Womack • HIGH PRIORITY STATUS • Objectives: • Sequence the bovine genome to 6x coverage. • Identify 100,000 single nucleotide polymorphisms (SNPs) • Use comparative information from cattle to identify new genes and • novel regulatory elements in humans, mice and rats. • Understand how genetic variation contributes to diverse phenotypes • and disease • Understand genetic interactions with environmental factors

19. COMPARATIVE TRIANGULATION

20. Informing Human Biology • Cattle have already played an extensive role in physiological and • biochemical research pertaining to human health • Understanding reproductive and pituitary hormones • Bovine insulin to treat human diabetes (Sanger et al. 1955) • Anticoagulant, Warfarin, in cattle with sweet clover disease • (Stahmann et al., 1941) • Identification of parathyroid hormone (Collip, 1925) • Demonstration of leuteotrophic effect of leutinizing hormone • (Wiltbank et al., 1961) • Growth promoting effect of growth hormone (Evans & Long, 1921) • Lactational effects of GH demonstrated in dairy cattle • Reproductive Techniques • superovulation, oocyte culturing, in-vitro fertilization • embryo maturation, transfer and freezing

21. Benefits to Human Health • The bovine model is relevant to human health research priorities such as obesity, female health, osteoporosis, and communicable diseases. • Will be invaluable to study host-pathogen interactions for food safety (e.g. E. coli O157-H7, Salmonella and Listeria) and agents that affect food security and human health (e.g. Foot and Mouth Disease, Mad Cow Disease)

22. Availability of the genome sequence will significantly reduce • the time needed to develop genetic tests • Novel therapeutics or management strategies could be • developed to leverage the underlying genetic information for • improved production efficiency • Will ultimately allow us to understand how networks of genes • interact with each other and the environment to affect animal • physiology (e.g. reproductive efficiency, bone structure, • growth rates, fat deposition, heat tolerance, pathogen resistance) Benefits to the Cattle Industry