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10/15/2018
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Prosser, October 2018
Dairy Genomics Update
Colorado State University, University of Florida, The Ohio State University, Cornell University, University of Illinois , Urbana‐Champaign, University of Wisconsin, Texas A&M University, Ross University
P Pinedo, J Santos, G Schuenemann, R Bicalho, R Chebel, K Galvao, R Gilbert, S Rodrigez‐Zas, G Rosa, C Seabury, J Fetrow, W Thatcher
Where we are coming from:
The problem
Genetic Selection for Fertility?
Matching Fertility and Genomics?
Sharing our results
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Preg rateAI rate
ConceptionRisk
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Reasons for this trend on declining dairy fertility?
o Anovulation
o Reduced fertilization
o Embryonic survivalLucy, 2001; VanRaden et al., 2004; Hare et al., 2006; Walsh et al., 20116
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Embryonic survival:
In women: 40‐60% of embryos lost
between fertilization and birth (Jarvis, 2016, 2017)
In dairy cows: 36% of embryos lost between d19 & d62 (Wiltbank et al., 2016)
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At least in part….
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Refocusing…
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Source: CDCB 201810
H
S
F
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The Elevation of an Industry, 2015 11
The producer’s mindset
1950’s trade show display (Michigan)
The key
Adopting Artificial Insemination
The Elevation of an Industry, 2015 12
The producer’s mindset is changing
1950’s trade show display (Michigan)
Non‐traditional traits
Use of genomics at the farm
The key
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Genetic Selection and Improved Fertility? It's not That Simple
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How much of the variation is due to genetics?
Getting the right data
Negative association with production?1
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3
Some pending questions…..
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Matching Fertility and Genomics:Sharing our results
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Genomic Selection for Improved Fertility of Dairy Cows with Emphasis on Cyclicity and Pregnancy
NIFA‐AFRI funded5 years
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Colorado State University, Cornell University, U. of Florida, U. of Minnesota, U. of Wisconsin, U. of Illinois at Urbana‐Champaign, Texas A&M AgriLife Research, Texas A&M University, The
Ohio State University
Pinedo PJ, Santos JE, Galvao K, Seabury C, Rosa JM, Bicalho RC, Gilbert RO, Schuenemann G, Chebel R, Thatcher
W, Rodriguez‐Zas S, Fetrow J
Award # 2012-02115 NIFA AFRI Translational Genomics for Improved Fertility of
Animals
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What was done?18
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11,733 cows calving in 16 farms located in 4 regions
• Cows calving from Nov 2012 to Oct 2014
• Warm season: May – July
• Cool season: Oct ‐ Dec
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Calvingrelated problems
7dDIM
BCS + BHBA +Metritis
Clinical Endometritis
28 DIM 35 DIM
BCSLamenessUS (CL)
Pregnancy Check
Re‐Check
32d post AI
60dpost AI
49 DIM
US (CL)
Prospective Approach
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Standardized definitions and times
Preg loss
And monthly milk yield!
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1. Develop a fertility database with genotypes and phenotypes based on direct measures of fertility in Holstein cows
Why?The objectives
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n = 11,733
+
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High‐density DNA analysis platform (777k)(n=3,600)
Identify the genes responsiblefor the trait or genetic markers close to the genes
How?
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2. Identify SNPs associated with fertility traits by use of genome‐wide analyses (GWAS)
3. To obtain genomic breeding values for selection for improved fertility
Why?The objectives
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Which are the successful cows?What is different in these cows?
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To put it simple…
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The effect of suboptimal health
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First lesson
0
5
10
15
20
25
30
Freq
uen
cy (%)
Health event26
22%27% 26%
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0
5
10
15
20
25
30
Freq
uen
cy (%)
Health event27
~45% of the dairy cows are diagnosed with a problem in the first 60 DIM
REP
Dystocia, twins, retained fetal membranes, metritis, and
clinical endometritis
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OTHSubclinical ketosis, mastitis, displaced abomasum, and
pneumonia
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REP 1
0.740.67
0.550.47
0
0.2
0.4
0.6
0.8
1
1.2
0 1 2 3 ≥ 4
Odds Ratio
Number of reproductive disorders events
OR for resumption of ovarian cyclicity (d50)
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OTH1
0.81
0.64
0.43
0
0.2
0.4
0.6
0.8
1
1.2
0 1 2 ≥3
Odds Ratio
Number of health events
OR for resumption of ovarian cyclicity
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1
0.750.70
0.670.46
0
0.2
0.4
0.6
0.8
1
1.2
0 1 2 3 ≥ 4
Odds Ratio
Number of repro disorders events
OR for pregnancy at first AI
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REP
1 0.920.81
0.52
0
0.2
0.4
0.6
0.8
1
1.2
0 1 2 ≥3
Odds Ratio
Number of health events
OR (95% CI) for pregnancy at first AIOTH
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0
0.5
1
1.5
2
2.5
3
0 1 2 3 ≥ 4
Odds ratio
Number of repro disorders events
11.42
1.771.65
2.50
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REP
Mean farm incidence of LAM (≥3) was 11.9%
Frequencies (%) for lameness scores
n = 11,733 cows
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1-2 ≥3
Normal (NOR) Lame (LAM)
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Lame (LAM)
Lame (LAM)
Gone?
Fertility?
Some traits looking interesting
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Lesson two
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Transrectal ultrasonography at 40±3 and54±3 d postpartum.
The presence of a corpus luteum was considered as indication for resumption of ovarian cyclicity
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Pinedo et al, 2018
If cycling at 50 DIM :
• Reduced days open (132 vs. 150 d)
• Higher pregnancy at first (OR = 1.92) and second (OR = 1.42) A.I.
• Lower culling after 50 DIM (OR = 0.79)
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Bacterial infection: Purulent uterine discharge (≥21 DIM)
Mean farm incidence of clinical
endometritis was 26%
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
Resumption ofovarian cyclicity
Pregnancy at firstAI
Pregnancy atsecond AI
Pregnancy loss atfirst AI
Odds Ratio
Effect (OR) of clinical endometritis on fertility
0.66 0.630.79
1.60
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Pregnancy at 1st AI
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Season
Parity
Retained placenta
Metritis
Lameness 35d
Clinical endometritis
Cyclic
LOW for cows in the lowest quartile (RI <0.26) MEDIUM (0.26 ≥ RI ≤ 0.39)
and HIGH (RI > 0.39)
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Freq
uenc
ies
(%) o
f Re
prod
ucti
ve O
utco
me
Num
ber
of D
ays
Ope
n
Days open
Any genomic associations?
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Lesson three
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BHB(SUBCLINICAL KETOSIS)
Proportion of Additive Genetic Variance Explained by Windows of 50 Adjacent SNPs Distributed by
Chromosomes for …
METRITIS
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Genetic Improvement of Dairy Cattle. C. J. Wilcox, D. W. Webb, and M. A. DeLorenza UF IFASMarti and Funk, 1994; Kadarmideen et al., 2003; Jamrozik et al., 2005
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
Milk Yield
Milk fat
Protein
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4
Conception rate
Reproductive Efficiency
Mastitis resistance
Dairy character
1/4
1/20
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Searching for genomic associations
DIM at estrush2 = 15%
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Milkh2 = 25%
Searching for genomic associations
Days openh2 = 14%
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Milkh2 = 25%
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16 genes on bovine chromosomes 1, 3, 6, 10, 11, 12, 14, 15, 22, and 29 were associated with the traits of interest.
Trait HeritabilityRetained placenta 9%
Metritis 6 ‐ 10%
Clinical Endometritis 10%
Resumption of cyclicity 7 ‐ 35%
Mastitis 5%
Days Open 10 ‐ 14%
Pregnancy 60 d after first AI 11 ‐ 20%
Reproductive index 12%
Brito et al., 201849
Genetic relationships among reproductive traits
Retained Placenta Metritis
Retained Placenta C. Endometritis
Lameness C. Endometritis
C. Endometritis Pregnant 60Cyclic Pregnant 60
Cyclic C. Endometritis
Brito et al., 201850
↑
↑
↑
↑
↑↑
↑
↑
↑
↑
↓
↓
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Lying time?
High milk yield
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Low milk yield
Eating time?
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Good transition
Bad transition
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Rumination time?
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Good transition
Bad transition
54Seabury et al., 2018
Good BCS HealthyCycling Pregnant MetritisPregnancy loss
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• Health during early lactation is key for fertility, milk yield, and survival
• Genetic variation is associated with reproductivetraits allowing for genomic selection for improved fertility
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• Interesting relationships and new traits to be explored
• More to come!
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• Co‐Investigators in Genomic Selection for Improved Fertility of Dairy Cows With Emphasis on Cyclicity and Pregnancy
• Dairy farmers in CA, NY, MN, WI, OH, FL, TX
• Undergrad and graduate students
This research was funded by USDA‐NIFA Agriculture and Food Research Initiative
Award # 2013-02115 NIFA AFRI Translational Genomics for Improved
Fertility of Animals
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??? !!
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Thanks!pinedop@colostate.edu 59
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