building the genomics toolbox for a livestock genome - james kijas
DESCRIPTION
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
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