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Breeding and genomics in ILRI biosciences
research
Steve Kemp
ILRI BioSciences Day, Nairobi, 27 November 2013
Livestock diversity
Livestock diversity

Genome sequence
determines characteristics:
• Disease resistance
• Drought tolerance
• Productivity
Livestock diversity
Genome sequence MOSTLY determines
characteristics, but what determines
productivity in a given system?
•
•
•
•

Genetics ?
Feed ?
Health ?
Management ?

That is a meaningless
question!
Disease resistance

Boran

N’Dama

Bovins
Cattle
Glossines
Tsetse
Bovins et Glossines
Cattle and tsetse
Contribution of 10 genes from Boran and N’Dama
cattle to reduction in degree of trypanosomosis
Boran (relatively susceptible)

15
10
5
0
-5
-10
-15

N’Dama (tolerant)

15
10
5
0
-5
-10
-15

The N’Dama and Boran each contribute trypanotolerance alleles at 5
of the 10 most significant QTL, indicating that a synthetic breed could
have even higher tolerance than the N’Dama.
Alignment of N’Dama ARHGAP15 with
homologues
H

P mutation at AA282

Cow NDama
KFITRRPSLKTLQEKGLIKDQIFGSPLHTLCEREKSTVPRFVKQCIEAVEK
Cow Boran
KFITRRPSLKTLQEKGLIKDQIFGSHLHTLCEREKSTVPRFVKQCIEAVEK

Human
KFISRRPSLKTLQEKGLIKDQIFGSHLHTVCEREHSTVPWFVKQCIEAVEK
Pig
Chicken

KFITRRPSLKTLQEKGLIKDQIFGSHLHTVCERENSTVPRFVKQCIEAVEK
KFISRRPSLKTLQEKGLIKDQIFGSHLHLVCEHENSTVPQFVRQCIKAVER

Salmon
KFISRRPSMKTLQEKGIIKDRVFGCHLLALCEREGTTVPKFVRQCVEAVEK
N'Dama (n = 35) Boran (n = 28)
Gene frequency
282P-Allele
0.990
0.125
282H-Allele
0.010
0.875
Alignment of N’Dama ARHGAP15 with
homologues
That mutationof AA282
H
P piece at work

took a lot of time and money.

Cow NDama
What has it really achieved?
KFITRRPSLKTLQEKGLIKDQIFGSPLHTLCEREKSTVPRFVKQCIEAVEK
Cow Boran
KFITRRPSLKTLQEKGLIKDQIFGSHLHTLCEREKSTVPRFVKQCIEAVEK

Human
KFISRRPSLKTLQEKGLIKDQIFGSHLHTVCEREHSTVPWFVKQCIEAVEK
Pig
Chicken

KFITRRPSLKTLQEKGLIKDQIFGSHLHTVCERENSTVPRFVKQCIEAVEK
KFISRRPSLKTLQEKGLIKDQIFGSHLHLVCEHENSTVPQFVRQCIKAVER

Salmon
KFISRRPSMKTLQEKGIIKDRVFGCHLLALCEREGTTVPKFVRQCVEAVEK
N'Dama (n = 35) Boran (n = 28)
Gene frequency
282P-Allele
0.990
0.125
282H-Allele
0.010
0.875
The technology behind such ‘gene discovery’ has
been transformed
The technology behind such ‘gene discovery’ has
been transformed
The technology behind ‘gene delivery’ has NOT
been transformed
It is not rocket science!
But that does not mean it is easy..
…and we need a complete pipeline
The pipeline is therefore incomplete
Genome sequence is now easy to obtain.

Phenotype information is now HARDER to obtain.
We need both.
Breeding and genomics in ILRI biosciences research
The technology behind ‘gene delivery’ has NOT
(entirely) been transformed
TALENS technology.

Is somewhere along that pipeline and allows us to perform
‘precision crossbreeding’, or gene editing.
We can now swap alleles at 100 genes in one go.
But we don’t have 100 candidate SNPs, because the
pipeline is dry.

But we do have 2!
We need to re-establish a genetics pipeline.
We need to re-establish a genetics pipeline
Sequence

Conserve
Phenotype
Function

Deliver to an animal
Deliver to the user

What traits?
What species?
What breeds?
What target systems?
Where to look for
variation?
Livestock diversity

A cow is mostly non-cow:
•Rumen sequence PARTLY
Genome
•Skin
determines characteristics:
•Milk
• Disease resistance
•Soil
• Drought tolerance
• Productivity
Metagenomes play a role and interact
with each other.
So ‘describing a cow, suddenly became
much more fun.

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Breeding and genomics in ILRI biosciences research

  • 1. Breeding and genomics in ILRI biosciences research Steve Kemp ILRI BioSciences Day, Nairobi, 27 November 2013
  • 3. Livestock diversity Genome sequence determines characteristics: • Disease resistance • Drought tolerance • Productivity
  • 4. Livestock diversity Genome sequence MOSTLY determines characteristics, but what determines productivity in a given system? • • • • Genetics ? Feed ? Health ? Management ? That is a meaningless question!
  • 6. Contribution of 10 genes from Boran and N’Dama cattle to reduction in degree of trypanosomosis Boran (relatively susceptible) 15 10 5 0 -5 -10 -15 N’Dama (tolerant) 15 10 5 0 -5 -10 -15 The N’Dama and Boran each contribute trypanotolerance alleles at 5 of the 10 most significant QTL, indicating that a synthetic breed could have even higher tolerance than the N’Dama.
  • 7. Alignment of N’Dama ARHGAP15 with homologues H P mutation at AA282 Cow NDama KFITRRPSLKTLQEKGLIKDQIFGSPLHTLCEREKSTVPRFVKQCIEAVEK Cow Boran KFITRRPSLKTLQEKGLIKDQIFGSHLHTLCEREKSTVPRFVKQCIEAVEK Human KFISRRPSLKTLQEKGLIKDQIFGSHLHTVCEREHSTVPWFVKQCIEAVEK Pig Chicken KFITRRPSLKTLQEKGLIKDQIFGSHLHTVCERENSTVPRFVKQCIEAVEK KFISRRPSLKTLQEKGLIKDQIFGSHLHLVCEHENSTVPQFVRQCIKAVER Salmon KFISRRPSMKTLQEKGIIKDRVFGCHLLALCEREGTTVPKFVRQCVEAVEK N'Dama (n = 35) Boran (n = 28) Gene frequency 282P-Allele 0.990 0.125 282H-Allele 0.010 0.875
  • 8. Alignment of N’Dama ARHGAP15 with homologues That mutationof AA282 H P piece at work took a lot of time and money. Cow NDama What has it really achieved? KFITRRPSLKTLQEKGLIKDQIFGSPLHTLCEREKSTVPRFVKQCIEAVEK Cow Boran KFITRRPSLKTLQEKGLIKDQIFGSHLHTLCEREKSTVPRFVKQCIEAVEK Human KFISRRPSLKTLQEKGLIKDQIFGSHLHTVCEREHSTVPWFVKQCIEAVEK Pig Chicken KFITRRPSLKTLQEKGLIKDQIFGSHLHTVCERENSTVPRFVKQCIEAVEK KFISRRPSLKTLQEKGLIKDQIFGSHLHLVCEHENSTVPQFVRQCIKAVER Salmon KFISRRPSMKTLQEKGIIKDRVFGCHLLALCEREGTTVPKFVRQCVEAVEK N'Dama (n = 35) Boran (n = 28) Gene frequency 282P-Allele 0.990 0.125 282H-Allele 0.010 0.875
  • 9. The technology behind such ‘gene discovery’ has been transformed
  • 10. The technology behind such ‘gene discovery’ has been transformed
  • 11. The technology behind ‘gene delivery’ has NOT been transformed It is not rocket science! But that does not mean it is easy.. …and we need a complete pipeline
  • 12. The pipeline is therefore incomplete Genome sequence is now easy to obtain. Phenotype information is now HARDER to obtain. We need both.
  • 14. The technology behind ‘gene delivery’ has NOT (entirely) been transformed TALENS technology. Is somewhere along that pipeline and allows us to perform ‘precision crossbreeding’, or gene editing. We can now swap alleles at 100 genes in one go. But we don’t have 100 candidate SNPs, because the pipeline is dry. But we do have 2! We need to re-establish a genetics pipeline.
  • 15. We need to re-establish a genetics pipeline Sequence Conserve Phenotype Function Deliver to an animal Deliver to the user What traits? What species? What breeds? What target systems? Where to look for variation?
  • 16. Livestock diversity A cow is mostly non-cow: •Rumen sequence PARTLY Genome •Skin determines characteristics: •Milk • Disease resistance •Soil • Drought tolerance • Productivity Metagenomes play a role and interact with each other. So ‘describing a cow, suddenly became much more fun.