PGI markers for fertility and reproductive longevity: An opportunity to improve replacement rates

1
PGI markers for fertility and reproductive
longevity An opportunity to improve
replacement rates

• Dr Hein van der Steen
• CEO of PGI
• Truro, Nova Scotia

2
Solving the Problem of High Replacement Rates in
Dairy Herds
1. Selection for milk production, inbreeding,
larger herds and poorer management
3
Buying and selling cows?
Target?
By chance 12 months figure
Robert Moore, Valacta, January 2009
4
Number of cows reaching a certain lactation
number, 1st calving in 1980 or 1994, US
Difference 6 months herd life
145 /cow/ year
Lactation number
Hare et al. (2006) JDS 89(9)3713-3720
5
Culling rate, CDN (2008)
Annual incr. 9 x 0.96 8.6 12Lact 10.6
Profit -261/cow/yr
6
The Solution

• PGI has identified genes that affect Fertility
  and RL

• PGI will use the genes to develop genetic
  markers for FRL

• Those with a major impact on fertility and
  stayability will be combined in an index that
  predicts the FRL of the cow

• The best calves can be kept as herd replacements
  or sold at a premium

• The best cows can be used to produce herd
  replacements

• Using sexed semen and embryo technology will
  improve the value of the marker index

7
Underlying Technology

• Livestock markers

• Human markers

• Drug discovery IP

8
Mouse versus Cow
Mouse 30 Generations
Cattle (US data) 3 Generations
Lactation
9
Mouse versus Cow
0 70
400 days
Control mouse
1
2
3
4
5
Selection line mouse
1
3
2
4
5
6
7
8
9
10
Improved fertility and RL
0 1 2 3 4 5
6 7 8 9 years
Cows RR 50 Cows RR 25
1
2
1
2
4
3
Use information from mouse model to improve cattle
10

• The Benefits
• of
• Extended Reproduction

11
The Genetics of Stayability

• how much of stayability is genetic?

• how much of this in turn is associated
  specifically with RL? 

• RL/stayability is a complex trait - heritability
  ranges
• from .05 to .50, depending on how it is defined
  and
• the relative influence of the genetic and
  environmental
• factors that affect it

Genetics and management both good cows are
culled for production reasons before RL becomes
a bottleneck gtgtgt the
heritability is low
As the genetic value for RL deteriorates due to
selection for milk production, poorer management
due to larger herd size, poorer stockmanship,
etc, the genetic value in RL does get expressed
gtgtgt its heritability is higher
12
Impact of Replacement Rate on of 2nd versus
3rd Lactation
30 35
40 45 50

13
Financial impact of change in RR
Better reproductive longevity More
lactations/cow Reduced replacement
costs Increased milk production
14
The Value

• Improved stayability through
• Use of the marker index for herd replacement
  strategy
• Use of semen from bulls with high marker index
  for FRL

• Decrease of involuntary culling
• Increase of voluntary culling
• Longer herd life and more optimal
  replacement strategy

15
RL ET and Sexed Semen

• Improved Fertility and Reproductive Longevity
  results in higher success rate with AI, sexed
  semen and ET
• Sexed semen and ET create an opportunity to use
  the (very) best cows for the production of
  replacement heifers
• ET creates an opportunity to produce surplus
  heifers with high FRL-index values for sale

16
Balance the role of semen and herd strategy

• Semen
• Accuracy of PTA for production is high
• Accuracy of FRL-marker Index is medium
• Cows
• Accuracy of PTA for production is medium
• Accuracy of FRL-marker Index is medium
• So more emphasis on FRL at herd level

17
How to develop the marker index for fertility and
reproductive longevity?

• PGI has license for embryo survival gene (STATA5)
  from WARF (U of Wisconsin)
• IVF, wrong genotype 30 ES
• IVF, correct genotype 60 ES
• PGI has identified RL genes using the mouse model
• 50 Candidate genes for FRL

18
Holstein project

• SNP marker discovery and 1st stage validation
• 2nd Stage validation
• Marketing

Phase I
Phase II
Marketing
Mouse
19
Phase-1 SNP discovery and 1st stage validation
. . .
50 genes

Number of cows
Number of bulls
L
H
L
H
Poor Good
Poor
Good Fertility and RL
Fertility and RL
20
Phase-1 SNP discovery and 1st stage validation
H/L pools
50 genes

Sequencing
ALL markers for the 50 genes Allele frequency
contrasts between H and L pools
1.0 0.8 0.6 0.4 0.2 0.0
M1 M2 M3 M10,000
Gene variant 1
H L
21
Phase-2 Individual validation

• 386 most promising SNPs
• 3,000 bulls, 3000 cows
• DNA and Data
• Association analyses
• Genes that have impact
• Markers to exploit the gene effects
• Marker panel for commercial use

22
PGI marker panel for FRL versus genomic selection
Impact of FRL marker panel
Impact genomic selection
0
Genetic Progress Milk Production Traits
Old program
Old GS
Old GS FRL panel
Negative 0 positive
Genetic progress fertility and RL
23
Use of FRL marker panel
Replacement strategy Optimal improved Busi
ness strategy result
Reverse the negative trend