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

What will mapping What will mapping the genome mean to the genome mean to

the industry?the industry?

Clare A. Gill, Ph.D.Department of Animal Science

Texas A&M University

OutlineOutline Current Status of the Bovine Genome Current Status of the Bovine Genome

MapMap International Bovine BAC Map ConsortiumInternational Bovine BAC Map Consortium

Strategy for Genome SequencingStrategy for Genome Sequencing

Industry ApplicationsIndustry Applications

30 pairs of chromosomes

10-30m

Bovine Genome

30 pairs of chromosomes

3,000,000,000 base pairs

30,000 - 50,000 genes

Genes make up less than10% of the genome

Base changes can affectphenotype

Bovine Genome

Mapping

Sequencing

Bioinformatics

Genetic Linkage map of bovine chromosome 1

BM6438

BM4307

TGLA57

RM95

BL28

BM1312

TGLA49

BM6506

CSSM32

MAF46

INRA117

DIK70

URBO14

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

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

BAC FingerprintsBAC Fingerprints http://www.bcgsc.bc.ca/projects/bovine_mapping/http://www.bcgsc.bc.ca/projects/bovine_mapping/

The current database contains 294,652The current database contains 294,652 clonesclones 45,000 Angus BACs contributed by TAMU45,000 Angus BACs contributed by TAMU >1000 loci mapped using TAMU library>1000 loci mapped using TAMU library

280,000 BACs will be end sequenced280,000 BACs will be end sequenced 100,000 BAC ends will be contributed by TAMU100,000 BAC ends will be contributed by TAMU

Cattle is the only animal species that will have the BAC Cattle is the only animal species that will have the BAC Map completed prior to genomic sequencingMap completed prior to genomic sequencing

BAC End SequencingBAC End Sequencing

International BAC Map International BAC Map Consortium MembersConsortium MembersUSDA-MARCUSDA-MARC INRAINRA

BCGSCBCGSC AgResearchAgResearch

TIGRTIGR Roslin InstituteRoslin Institute

Baylor College of MedicineBaylor College of Medicine CSIROCSIRO

Texas A&M UniversityTexas A&M University

University of AlbertaUniversity of Alberta plus researchers fromplus researchers from

University of IllinoisUniversity of Illinois Brazil & JapanBrazil & Japan

DNA Markers = DNA Markers = BookmarksBookmarks

Sequence = Words on Page

The Bovine Genome Project

From Green (2001) Nat. Rev. Genet. 2: 573-583.

Bovine Genome Sequencing Initiative

White Paper submitted to NIHGibbs, Weinstock, Kappes, Schook, Skow & WomackHIGH 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 HealthBenefits to Human Health

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

Will be invaluable to study host-pathogen interactions for Will be invaluable to study host-pathogen interactions for food safety (e.g. E. coli O157-H7, Salmonella and Listeria) food safety (e.g. E. coli O157-H7, Salmonella and Listeria) and agents that affect food security and human health (e.g. and agents that affect food security and human health (e.g. Foot and Mouth Disease, Mad Cow Disease)Foot and Mouth Disease, Mad Cow Disease)

Benefits to the Cattle IndustryBenefits 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)