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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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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

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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