building the genomics toolbox for a livestock genome - james kijas

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James Kijas FOAM March 2014 Building the genomics toolbox for a livestock genome

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Researchers motivated to identify genes that control differences between individuals rely on a genomics toolbox. Really useful tools include i) a reference genome assembly ii) information about where the genes and other features reside inside that genome assembly and iii) a way to collect large scale data describing the differences between genomes from different individuals. A team inside CSIRO has been developing each of these tools for the sheep genome, and putting them to work to understand what contributes to variation in production traits (eg wool growth and meat quality). The talk will focus on the approach taken over the last 5 years to build the various components of the toolkit. This has consequences for the development of genomic resources in other species which may currently have fewer available tools.

TRANSCRIPT

Page 1: Building the genomics toolbox for a livestock genome - James Kijas

James Kijas FOAM March 2014

Building the genomics toolbox

for a livestock genome

Page 2: Building the genomics toolbox for a livestock genome - James Kijas

What makes individuals different?

+ E

Page 3: Building the genomics toolbox for a livestock genome - James Kijas

Linkage Map

Reference Genome

Gene Expression Array

SNP Genotyping Array

What is the most useful component to put into the toolbox? Focus on two components

Genome Re-sequencing

Broad Institute

Page 4: Building the genomics toolbox for a livestock genome - James Kijas

Tellam Ingham McWilliam Dalrymple

Jiang Yu Kijas

Dalrymple McWilliam

2004 2005 2006 2007 2008 2009 2010 2011 2012

Chicken Sheep Cattle Pig Goat

Comparative genome

Page 5: Building the genomics toolbox for a livestock genome - James Kijas

2004 2005 2006 2007 2008 2009 2010 2011 2012

Shotgun Sanger based BAC physical map

Chicken

Page 6: Building the genomics toolbox for a livestock genome - James Kijas

2005 2006 2007 2008 2009 2010 2011 2012 2013

Comparative genome

Sheep DNA Fragments

NG Sequencing

340K mutations

2014

Reference Assembly v3.1

Under Review (Science)

Page 7: Building the genomics toolbox for a livestock genome - James Kijas

GWAS for Disease

23 cases 23 controls

Test and remove PITX3 mutants through breeding

Page 8: Building the genomics toolbox for a livestock genome - James Kijas

Selection Sweeps

Page 9: Building the genomics toolbox for a livestock genome - James Kijas

Evolution

11 K years

200 years

Page 10: Building the genomics toolbox for a livestock genome - James Kijas
Page 11: Building the genomics toolbox for a livestock genome - James Kijas

What is the most useful component to put into the toolbox? Should we build a SNP chip or a Reference Genome first?

1. Do we have the skills, time and cash? 2. What is the objective? 3. Is there a reference genome for a related lineage?

Page 12: Building the genomics toolbox for a livestock genome - James Kijas

Reference Genome SNP Genotyping Array Tool

Required Resources

Institutional Level Skim Sequence / RRL / Pooling Common analytical expertise Partner with a life science co. $ Thousands – 10s K

International Consortium Species Specific Physical Map - radiation hybrid map - optical map - linkage map - BAC library Deep Sequence High-end analytical expertise $ Millions

1. Do we have the skills, time and cash?

Page 13: Building the genomics toolbox for a livestock genome - James Kijas

Reference Genome SNP Genotyping Array Tool

Applications

Genetic Diversity Population Substructure Gene Flow Between Groups Breeding Programs GWAS for Major Genes

Genome Evolution Gene Regulation Proteomics Integration Platform

2. What is the objective?

Page 14: Building the genomics toolbox for a livestock genome - James Kijas

Conservation & Management

Food security & Productivity

Breeding & Adaptation

Disease Prevention

2. What is the objective?

Page 15: Building the genomics toolbox for a livestock genome - James Kijas

3. Is there a reference genome sequence for a related lineage?

yes

Page 16: Building the genomics toolbox for a livestock genome - James Kijas

3. Is there a reference genome sequence for a related lineage?

If no: - can still produce a SNP chip (all v all approach) - limited utility for some applications (eg GWAS)

- increases the rationale for building a reference genome assembly

Page 17: Building the genomics toolbox for a livestock genome - James Kijas

Conclusions - tools and their applications

- criteria for planning how to populate the toolbox

Thanks The International Sheep Genomics Consortium

Page 18: Building the genomics toolbox for a livestock genome - James Kijas