Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and...

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Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart Ducro Piter Bijma René van Weeren Hans van Tartwijk KWPN

Transcript of Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and...

Page 1: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Defining osteochondrosis and its

genetic background

Ilse van GrevenhofAnimal Breeding and Genomics Centre

Bart Ducro

Piter Bijma

René van Weeren

Hans van Tartwijk

KWPN

Page 2: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

What is OC?

Health problem in horses

Disturbance of ossification

In joints of young growing animals

Previous studies show prevalences vary 7% – 64%

Definition OC

Number of joints, radiographs, locations

Preselected data sample

Page 3: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Aims

Assess prevalences Joint level

Animal level

Stallion level

Study relationship Left and right joint

Flattenings and fragments

Genetic parameters Heritabilities

Genetic correlations

Page 4: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Materials

Dutch Warmblood population

2005/ 2006

OC was scored in 811 yearlings

After ‘point of no return’ (~12 months)

Randomly selected sample

Yearlings descended from 32 stallions

22 - 28 yearlings per stallion

Young and old stallions

Dressage and show jumping stallions

Page 5: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Methods

Scored on categorical scale A to E (Dik et al., 1999)

A = Ideal

B = Smooth flattened bone structure

C = Irregular flattened bone structure

D = Small bony fragment

E = Large bony fragment

Page 6: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Material and methods

OC scored on: 8 joints

14 radiographs

28 locations

Stifle Left 5 locations

Right 5 locations

Hock Left 7 locations

Right 7 locations

Fetlock 1 location

Page 7: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Methods: transformation to continuous scale

Aims: Estimate heritabilities and relationships

Problem: Observations are categorical

Needed: Transformation of categorical to continuous scale

Method: Based on prevalences

Result: 3 continuous traits FLAT

FRAG

ALL (FLAT + FRAG)

For each joint

For the entire animal (all joints combined)

Page 8: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Results

Animal level

Worst animal had 11 out of 28 ‘ideal’ locations

Best animal had 28 out of 28 ‘ideal’ locations

Joint Percentage of animals with fully ‘ideal’ joints

Stifle 61%

Hock 69%

Fetlock 65%

Total 30%

Page 9: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Results

Sire level

Mean: 30% of yearlings show fully ‘ideal’ joints

Worst stallion had 12% of yearlings with fully ‘ideal’ joints

Best stallion had 58% of yearlings with fully ‘ideal’ joints

No difference between show jumping/ dressage stallions

Page 10: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Are there prospects for breeding?

Sires (n=32)

Phe

noty

pic

SD

Standardized EBV of sires (All joints combined)

-0.470.33

~58%

~12%

Page 11: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Cluster analysis

Relationships

Reduction of variables

Based on correlation matrix

Page 12: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

ALLHock

Front

Hind

Fetlock

Flat

Flat

Stifle

Frag

Front

Hind

Flat

FragR

L

R

L

R

Frag

L

R

L

R

L

L

L

R

L

R

R

1.0 0.20.6Proportion of variance explained

Page 13: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Cluster analysis

Clustering order:

Left and right joints most similar

FLAT and FRAG less similar

Joints least similar

Reduction from 16 to 6 variables

~0.63

Page 14: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Conclusions

Prevalences (% not ideal)

Varies between joints

Cluster analyses indicated:

Left and right joints can be combined in analyses

FLAT and FRAG should be separated in analyses

Large differences between stallions

Results hard to compare with literature

Definition OC

Number of joints, radiographs, locations

Page 15: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Statistical model

OC = µ + sex + vet + age + year + animal + e

OC is the continuous FLAT, FRAG or ALL for a joint or the entire animal

REsidual Maximum Likelihood (REML)

Pedigree N = 7799

Page 16: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Heritabilities

Joint h2 ALL (SE)

h2 FLAT (SE)

h2 FRAG (SE)

Animal 0.23 (0.09) 0.08 (0.06) 0.22 (0.09)

Stifle joint 0.05 (0.05) 0.07 (0.06) 0.02 (0.04)

Hock joint 0.36 (0.11) 0.15 (0.08) 0.26 (0.09)

Fetlock

joints

0.14 (0.08) 0.08 (0.10) 0.06 (0.07)

Page 17: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Heritabilities

Do we need to score left and right joints?

Heritabilities of left and right joints were highly similar

Combined h2 is higher (increase with 16%)

Do we need to score from A-E or will binary (0/1) do?

h2 entire animal: 0.23 0.15

Page 18: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Genetic correlations

Genetic correlation in entire animal

FLAT and FRAG was 0.80 (± 0.25)

Genetic correlations between joints

Stifle and hock joints: 0.59

Fetlock and other joints: 0.09 - 0.26

Page 19: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Which joints are relevant for breeding?

Stifle joint

High prevalence

High clinical relevance (low prognosis surgical treatment)

High SE for genetic correlation with hock joint (0.59 0.37)

Hock joint

High prevalence of fragments

High heritable

Fetlock joint

Intermediate heritable

Low genetic correlations (no correlated response)

Page 20: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Are both FLAT and FRAG relevant for breeding?

FLAT and FRAG

Although rg between FLAT and FRAG is high (0.80)

SE is large (0.25)

Heritabilities are substantially different

Page 21: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

What can be concluded?

For breeding, OC should be recorded in:

All 4 joints

Flattenings and fragments

Left and right joints

Scored in >2 categories

Page 22: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart
Page 23: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Linear OC value

0

0,1

0,2

0,3

0,4

-3 -2 -1 0 1 2 3

y-axis: probability

x-axis: standard deviation

part belonging to

percentage of

category A

A

B

CD E

-0.23

Page 24: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Locations Stifle

1. Lateral femoral trochlea

2. Medial femoral trochlea

3. Sulcus distal femur

4. Patella

5. Other locations

Hock 1. Sagittal ridge of distal tibia

2. Lateral trochlea of talus

3. Medial trochlea of talus

4. Lateral malleolus of tibia

5. Medial malleolus of tibia

6. Base of talus

7. Other locations

Fetlock Proximodorsal part of the sagittal ridge of 3rd metacarpal/metatarsal bone

Page 25: Defining osteochondrosis and its genetic background · 2010-11-26 · Defining osteochondrosis and its genetic background Ilse van Grevenhof Animal Breeding and Genomics Centre Bart

Radiographs

Stifle

Lateromedial

Anterior-posterior lateral oblique

Hock

Anterior-posterior

Lateromedial

Anterior-posterior lateral oblique

Fetlock

Lateromedial