Future Research in Genomics

Curt Van Tassell

AIPL Centennial Celebration

November 28, 2008

USDA Genomics Blueprint

Science to Practice

• Genome-enabled animal selection

Build a Better Black Box

New and Improved!

Phenotype?? Genotype!!

Predicted Genetic Merit

Holstein Genome Selection (August 2008)

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Predictor Bulls

Gap Bulls

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Cows

Numbers continue to increase

Reliability Gain by Breed

Trait HO JE BS

Net merit 23 9 3

Milk 23 11 0

Fat 33 15 5

Protein 22 4 1

Fat % 43 41 10

Protein % 34 29 5

Science to Practice• Genome-enabled animal selection

• Precision mating systems

– Embryonic selection– Non-additive genetic effects

• Cow data

• Precision Management Systems– Merial, Pfizer??

• Animal identity and traceability– Low density-SNP project

Low Density-SNP Project

• Collaboration with Illumina• 384 SNP assay using pooling

– ~96 dedicated to pedigree verification/traceability– 378 for genetic prediction

• Stages of development– Alpha – test of multiplex– Beta – 1-3 Groups Genotyping ~20K samples– Commercialization ~300K+/yr

• Implications– Obviate need for pedigree– Increase heritability of phenotypes?!

Discovery Science• Gene discovery

– Deleterious recessives– Causative mutations

Deleterious Recessives

Deleterious Recessives: Strategy

• Identify affected and closely related unaffected: case – control population

• Identify region as narrowly as possible• Obtain DNA for these animals• Fragment and label DNA• Recover for specific region in genome• DNA sequence using next-generation instrument• Total cost ~ $10,000 for DNA work• Proof of concept

– Build infrastructure– Next time more rapid`

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Causative Mutations

Discovery Science• Gene discovery

– Deleterious recessives– Causative mutations

• Functional genomics– Ongoing – e.g., gene atlas, microarrays– Next-generation sequencing

• Host-Pathogen interaction– Mastitis– Rumen microbes

• “Meta-genomics”

• Systems biology– The big picture

Gene Atlas Vitals

• 7.2 million tag types• ~85% of all tags map to genome• 6.5 % of the tag types map to within gene

boundaries• 61 % of the tags that map within gene

boundaries map to a single gene• Majority of genes show evidence of

alternative splicing

Tissue Specificity

Only in liverOf juvenile

Only in fetal adrenal

BGA Gbrowse Views

Infrastructure• Genomic tools

– Selection tools– Inbreeding management

• Databases and bioinformatics– Build large federated databases– Share information

• Animal resource populations– Large centralized populations– “Falconer” flock model, NPB

• Education and training– Critical!!

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USDA/CSREES/NRIUSDA/CSREES/NRI2006-35616-166972006-35616-166972006-35205-168882006-35205-168882006-35205-167012006-35205-16701

USDA/ARSUSDA/ARS1265-31000-081D1265-31000-081D1265-31000-090-00D1265-31000-090-00D5438-31000-073D5438-31000-073DAIPL LaboratoriesAIPL Laboratories

Paul Van RadenPaul Van RadenGeorge WiggansGeorge Wiggans

Merial, LtdMerial, LtdStewart BauckStewart Bauck

Bull Studs/NAABBull Studs/NAABABS GlobalABS GlobalAccelerated GeneticsAccelerated GeneticsAlta GeneticsAlta GeneticsCRI/GenexCRI/GenexSelect SiresSelect SiresSemex AllianceSemex AllianceTaurus ServiceTaurus Service

MARCMARCTim SmithTim SmithMark AllanMark AllanRenee GodtelRenee GodtelLinda FlathmanLinda FlathmanKevin TennillKevin TennillKevin BeaversKevin BeaversBob LeeBob LeeSteve SimcoxSteve SimcoxTara McDaneldTara McDaneld

MissouriMissouriJerry TaylorJerry TaylorBob SchnabelBob SchnabelStephanie McKayStephanie McKayJae Woo KimJae Woo KimMatt McClureMatt McClureMegan RolfMegan Rolf

Jared DeckerJared Decker

Acknowledgements

BARCBARCTad SonstegardTad SonstegardLakshmi MatukumalliLakshmi MatukumalliPaul VanRadenPaul VanRadenJeff O’ConnellJeff O’ConnellGeorge WiggansGeorge WiggansJohn ColeJohn ColeSteven SchroederSteven SchroederLarry ShadeLarry ShadeDan NullDan NullAlicia BertlesAlicia Bertles

IlluminaIlluminaMarylinn MunsonMarylinn MunsonCindy Taylor LawleyCindy Taylor LawleyChristian HaudenschildChristian Haudenschild