Building the genomics toolbox for a livestock genome - James Kijas

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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.

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James Kijas FOAM March 2014

Building the genomics toolbox

for a livestock genome

What makes individuals different?

+ E

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

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

2004 2005 2006 2007 2008 2009 2010 2011 2012

Shotgun Sanger based BAC physical map

Chicken

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)

GWAS for Disease

23 cases 23 controls

Test and remove PITX3 mutants through breeding

Selection Sweeps

Evolution

11 K years

200 years

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?

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?

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?

Conservation & Management

Food security & Productivity

Breeding & Adaptation

Disease Prevention

2. What is the objective?

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

yes

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

Conclusions - tools and their applications

- criteria for planning how to populate the toolbox

Thanks The International Sheep Genomics Consortium

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