Transcript loca 38

Reporting of Haplotypes with
Recessive Effects on Fertility
Paul VanRaden, Dan Null, Katie Olson, Jana Hutchison
Animal Improvement Programs Lab, Beltsville, MD
National Association of Animal Breeders, Columbia, MO
[email protected]
2011
2007
Introduction
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Five haplotypes with recessive
effects on fertility discovered
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Additive effects small and in EBVs
All populations already carry these
At least 19 countries have ‘health’
laws excluding carriers of defects
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Only countries that test are banned?
Import restrictions make little sense
Interbull annual meeting, Norway, August 2011 (2)
Paul VanRaden
2011
Recessive Defect Discovery
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Check for homozygous haplotypes
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•
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7 to 90 expected but none observed
5 of top 11 confirmed as lethal
936 to 52,449 carrier sire by carrier
MGS fertility records
3.0% to 3.7% lower conception rates
Some slightly higher stillbirth rates
Confirmed Brachyspina same way
Interbull annual meeting, Norway, August 2011 (3)
Paul VanRaden
2011
Haplotypes Affecting Fertility
Chromosome
Location
BTA
Mbase
%
HH1
5
62-68
4.5
Pawnee Farm Arlinda Chief
HH2
1
93-98
4.6
Willowholme Mark Anthony
HH3
8
92-97
4.7
Glendell Arlinda Chief,
Gray View Skyliner
JH1
15
11-16
23.4
Observer Chocolate Soldier
BH1
7
42-47
14.0
West Lawn Stretch Improver
Name
Carrier
Freq Earliest Known Ancestors
Interbull annual meeting, Norway, August 2011 (4)
Paul VanRaden
2011
Additive and Nonadditive Effects
on nonreturn rates or full gestation conception
Additive
Hapl- Effect
Sire x MGS Interaction
otype
CR
NR60 NR100 NR140 CR280
CVM
-0.12
-0.9
-1.5
-1.9
-2.9
BY
HH1
HH2
HH3
JH1
BH1
-0.46
-0.35
-0.36
-0.36
-2.22
-0.98
-2.2
-1.1
-1.7
-3.1
-3.7
-2.5
Interbull annual meeting, Norway, August 2011 (5)
-2.3
-1.6
-3.0
-3.4
-3.7
-3.7
-2.3
-2.0
-2.9
-3.4
-3.6
-2.9
-2.5
-3.1
-3.0
-3.2
-3.7
-3.4
Paul VanRaden
2011
Carrier Bulls with High Fertility
Haplo-
Conception Rates
type
BY
HH1
HH2
Bull
Ramos
Lucius
Colby
HH3
JH1
BH1
O-Man
Country
Payoff
Service Sire Heifer
N/A
+0.1
+3.1
+2.5
+2.2
+5.2
+0.6
-0.5
+1.5
Interbull annual meeting, Norway, August 2011 (6)
+2.1
+2.7
+1.5
Cow
+5.2
+2.5
+5.4
+3.5
+3.2
+3.4
Paul VanRaden
2011
Using Crossovers to Fine Map
75 marker haplotype (50K), about 5 Mbases
Source
Combined
With
Source
Suspect
Area
Carrier
Possible
Interbull annual meeting, Norway, August 2011 (7)
Paul VanRaden
2011
Crossovers used in Fine Mapping
Crossover haplotypes
Haplotype
That
combined
with
source
Within
suspect
area
That
contained
suspect
area
SNPs in
suspect
area
BY
10
66
31
28
HH1
8
51
26
39
HH2
9
38
15
25
HH3
3
54
0
70
JH1
10
22
19
17
BH1
0
4
0
74
Interbull annual meeting, Norway, August 2011 (8)
Paul VanRaden
2011
Detection Without Haplotyping
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3 methods to detect carriers:
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Use all genotypes and pedigrees
One at a time (ignore pedigree)
Find and test for causative mutation
Without vs. with haplotyping
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2.5% false positive, 0.05% false neg
Similar to Georges et al (2010)
Brachyspina haplotype test
Interbull annual meeting, Norway, August 2011 (9)
Paul VanRaden
2011
Detection with 3K Genotypes
500 carriers, 500 noncarriers, with imputation
BY
HH1
False
positive
(%)
0.0
0.4
False
negative
(%)
2.2
6.4
Error rate
(%)
1.1
3.4
HH2
HH3
JH1
0.0
0.2
0.4
1.8
2.8
6.4
0.9
1.5
3.4
Haplotype
Interbull annual meeting, Norway, August 2011 (10)
Paul VanRaden
2011
Conclusions
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Recessive defects found in each
breed (HH1, HH2, HH3, JH1, BH1)
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Officially reported in August
Most embryo losses < 60 days
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Breeders should select for fertility,
not against individual defects, and
mate carriers to noncarriers
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Crossovers used for fine mapping
Interbull annual meeting, Norway, August 2011 (11)
Paul VanRaden
2011