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

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

30 pairs of chromosomes  m

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

Bovine Genome MappingSequencing Bioinformatics

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

Grisart et al. (2001) Genome Res. 12:

BAC Fingerprints The current database contains 294,652 clones The current database contains 294,652 clones 45,000 Angus BACs contributed by TAMU 45,000 Angus BACs contributed by TAMU >1000 loci mapped using TAMU library >1000 loci mapped using TAMU library 280,000 BACs will be end sequenced 280,000 BACs will be end sequenced 100,000 BAC ends will be contributed by TAMU 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 Cattle is the only animal species that will have the BAC Map completed prior to genomic sequencing BAC End Sequencing

International BAC Map Consortium Members USDA-MARCINRA BCGSCAgResearch TIGRRoslin Institute Baylor College of MedicineCSIRO Texas A&M University University of Albertaplus researchers from University of IllinoisBrazil & Japan

DNA Markers = Bookmarks Sequence = Words on Page

The Bovine Genome Project From Green (2001) Nat. Rev. Genet. 2:

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

COMPARATIVE TRIANGULATION

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

Benefits to Human Health The bovine model is relevant to human health research priorities such as obesity, female health, osteoporosis, and communicable diseases. 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) 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)

Benefits to the Cattle Industry 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)