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1 Kratka povijest Opća procjena funkcionalnih osobina – TMI – biljezenje svojstava zdravlja Genomska procjena Metode – uzgojni program – Uzgoj u srodstvu Biljezenje svojstava zdravlja Gesundheitsmonitoring.Rind Short history Gen. evaluation for functional traits – TMI – health trait recording Genomic evaluation Methodology - breeding programme – inbreeding Health trait recording Gesundheitsmonitoring.Rind Sadržaj Content

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1

• Kratka povijest

� Opća procjena funkcionalnihosobina – TMI – biljezenjesvojstava zdravlja

• Genomska procjena

� Metode – uzgojni program –

� Uzgoj u srodstvu

• Biljezenje svojstava zdravlja

� Gesundheitsmonitoring.Rind

• Short history

� Gen. evaluation for functionaltraits – TMI – health traitrecording

• Genomic evaluation

� Methodology - breedingprogramme – inbreeding

• Health trait recording

� Gesundheitsmonitoring.Rind

Sadržaj Content

2

• Uzgojna procjena za funkcionalnudugovjecnost 95`

� Prva zemlja u svijetu!

• Predstavljena ukupna uzgojna vrijednost u 98`

� Miesenberger et al.

• Predstavljen RR-test daymodel 02`

� Emmerling und Lidauer

• Genetic evaluation forfunctional longevity in 95

� First country world-wide!

• Introduction of a total merit index in 98

� Miesenberger et al.

• Introduction of RR-testdaymodel in 02

� Emmerling und Lidauer

Prekretnice Milestones

• Predstavljanje pracenjazdravlja

� Bilježenje zdravstvenih svojstava

� Prve uzgojne procjene 10`

• Razvoj genomskeprocjene kod simentalca

� Prve službene procjene EBV u kolovozu 2011`

• Introduction of healthmonitoring

� Recording of health traits

� First genetic evaluations in 10

• Development of genomicevaluation in Fleckvieh

� First official genomic EBVs in August 2011

Prekretnice Milestones

3

Uzgojni trendovi Genetic Trends

65

70

75

80

85

90

95

100

105

110

115

90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05

Re

lati

vzu

chtw

ert

Geburtsjahrgang

GZW

MW

FIT

FW

otprilike 2.5 TMI bodova/godina ili 100 kg

mlijeka

• Strong genet. gains in milk

• Stable trends in fitness traits

• Jak genetski napredak u mlijeku

• Stabilan trend u funkcionalnim svojstvima

Uzgojni trendovi Genetic Trends

65

70

75

80

85

90

95

100

105

110

115

90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05

Re

lati

vzu

chtw

ert

Geburtsjahrgang

MW

ND

FRUm

ZZ

4

• Kontinuirane inovacije

• Kjuc: bilježenje, uzgojne procjene i uzgojni program

• Odlicni genetski napredak umlijeku

• Stabilni trendovi alineznacajan napredak u

funkcionalnim svojstvima

• Continuous innovations!

• Keys: recording, geneticevaluation and breedingprogramme

• Excellent genetic gains in milk

• Stable trends but no sub-

stantial gains in fitness traits

Zakljucci iz osvrta Conclusions from

review

• Austrija: Projektfinanciran od FFG

• Njemacka: FUGATO+ Projekt Genotrack

• Zajednicki izvorreferentnih bikova od2010` na ovamo

• Austria: Project financed byFFG

• Germany: FUGATO+ Project Genotrack

• Common pool of referencesires from 2010 onwards

Genomska selekcija Genomic selection

5

• Razvoj logistike,metodologije, vrednovanja podataka genotipova, GS-solver

• U službenoj fazi, mjesečneprocjene kandidata, trirekalibracije godišnje

• Službena primjena, kolovoz2011`

• Development of logistics, methodology, validation of genotype data, GS-solver

• In official phase, monthly estimation of candidates, three recalibrations per year

• Official implementation, August 2011

Primjena Implementation

Rinderdatenverbund (RDV) (LKV Bayern, ZuchtData)

Breeders Association•Application Form (AF)

•Blood tubes with Barcode

AUT: Delivery from farm to

AIT• DNA-Pep.

• Storage

DNA – Lab (AIT)

SNP – Lab

(GeneControl)

Pla

tes

(24

er-

un

its)

(ext

ract

ed

DN

A)

Betrieb

TAApplication Form

Blood tube(Barcode)

Farm/BreederDEU: Central collection and shipping via

GeneControl to AIT

Interface:

Rinderdatenverbund (RDV) –

lab data base

Results:

gdZW, goZW

HB-DB SNP-DB

gdZW | goZW

Validation (LfL)

Genetic Evaluation Centers

Logisticki aspekti

(nach F. Reinhardt, und C. Egger-Danner)

Logistical Aspects

6

• x • DYDs and deregressedproofs as phenotypes

• G-BLUP for all traits� no substantial superiority

of Bayesian approaches

• Theoretical reliabilities obtained from model solutions

• Blending using index approach suggested by VanRaden

x Methodology

Genomski protok

podaci

rezultata

SNP podaci

genomische ZWSgenomska procjena

konvencionalna

procjena

direktna genomska

vrijednost gdZWkonvencionalna EBV

DYD; deregressed proof

genomiski optimizirana

vrijednost goZW

pedigre podaci

Genomic workflow

7

• Svi bikovi

• Genotipizirani bikovi

• AI bulls

• Genotyped bulls

Genotipski izvor Genotype pool

75-90% svih dostupnih bikova

Pouzdanosti Reliabilities

100

110

120

130

140

150

160

30 40 50 60 70 80 90 99

Datenreihen1

Datenreihen3

66% Confidence Int.

95% Confidence Int.

pedigree index genomic EBV proven EBV

130

uzg

ojn

a

vri

jed

no

st

Pouzdanost uzgojne

vrijednosti

8

Merkmal | Svojstvo PI-Si goZW-Si ∆∆∆∆ Si

GZW | Uk.uzg.vrijedn. 38 62 24 (63%)

MW | indeks mlijeka 38 64 26 (68%)

FW | indeks mesa 31 60 29 (94%)

FIT | indeks fitnesa 31 59 28 (90%)

ND | dugovjecnost 24 47 23 (96%)

FRM | plodnost mat. 24 44 20 (83%)

FU | noge i papci 28 55 27 (96%)

EU | vime 30 58 28 (93%)

Nivo pouzdanosti Reliability gain in

candidates

• Nivo pouzdanosti manji u usporedbi sa Holsteinom����Ne

• Funkcionalna svojstva pokazujurelativno velik napredak u pouzdanosti

• Reliability gains lower as compared to Holstein ����Ne

• Fitness shows larger relative gain in reliability

konventioneller ZWconventional EBVkonventioneller ZWconventional EBV

Pedigreeindexpedigree index

konventioneller ZWkonvencionalniEBV

Pedigreeindexpedigre indeks

genomischer ZW (goZW)genomskiEBV (goZW)

2 Punkte2 boda

Genetski trendovi (TMI) Genetic trends (TMI)

• Dobar genetski napredak kod mladih bikova

• PI over estimates by ~ 2 pnts

• Good genetic gain in young bulls

• PI over estimates by ~ 2 pnts

9

ZW Stiere GJ 02-05EBV bulls BY 02-05

ZW Stiere GJ 02-05EBV bulls BY 02-05goZW Wartestiere GJ 06-09goZW bulls BY 06-09

ZW Stiere GJ 02-05EBV bulls BY 02-05

goZW Kandidaten GJ 10-11goZW candidates BY 10-11

goZW Wartestiere GJ 06-09goZW bulls BY 06-09

top 10% of candidates selected

Odabranih 10% vrhunskih

kandidata

(nach R. Emmerling)

goZW po grupama

bikova

goZW by bull group

• no GS ���� Referenca� Trenutni uzgojni program� TMI + direktna svojstva zdravlja

Optimiziranje

uzgojnog programa

Optimization of

breeding programme

• no GS ���� Reference� Current breeding programme� TMI + direct health traits

Testanteil in %Osjemenjivanje mladim

bikovima

Jungstiere als TSV Mladi bikovi kao bikovski

ocevi

GS-BASIS 40 0

GS-1 40 50

GS-2 70 0

GS-3 70 50Egger-Danner und Willam, 2011

10

Novčani genetski

napredak i GI

Monetary genetic

gain and GI

0

1

2

3

4

5

6

0

20

40

60

80

100

120

140

1 2 3 4 5

mon ZW/Jahr in % GI in Jahren

aktuellesZuchtprogramm

Trenutni uzgojni program

40% TA;0% JS-TSV

GS-BASIS

40% TA;50% JS-TSV

GS - 1

70% TA;50% JS-TSV

GS - 3

70% TA;0% JS-TSV

GS - 2

+19% +25% +23% +29%

Egger-Danner und Willam, 2011

0

10

20

30

40

50

60

70

80

1 2 3 4 5

Milch Fleisch Fitness

Napredak u raznim

svojstvima

Gains in different

trait blocks

11% 13,8% 14,4% 15,1%

aktuelles Zuchtprogramm

Trenutni uzgojni program

40% TA;0% JS-TSV

GS-BASIS

40% TA;50% JS-TSV

GS - 1

70% TA;50% JS-TSV

GS - 3

70% TA;0% JS-TSV

GS - 2

14,7%

Egger-Danner und Willam, 2011

11

FV-Calibration:

birth years 1990-2008

ΔF=0,38%/5 years

IBS-Matrix

Uzgoj u srodstvu Inbreeding

•Nadjeno u literaturi :• 1% povećanja uzgoja u srodstvu po

generaciji. �Ne=50• Nema teoretske baze!

• Found in literature:• 1% increase in inbreeding per

gen. �Ne=50• No theoretical basis!

• EBV weights 3 info-sources:

• High weight on w1 ����

stronger inbreeding!

• High weight on Mendelian Sampling ���� reduced inbreeding rate

PROGwPAwa

PROGwYDwPAwa

**ˆ

bullsfor traitsproductionmilk

***ˆ

21

321

+=

++=

Mendelian Sampling Term

• EBV weights 3 izvorainformacija:

• Veci naglasak na w1 ���� veciuzgoj u srodstvu!

• Veci naglasak na mendelejevom uzorkovanju���� manji postotak uzgoja u srodstvu

Uzgoj u srodstvu Inbreeding

12

• genomic: Information on Mendelian Sampling for young bulls ����SNP-Markers

• how much? size of calibration, Ne, marker spacing, quality(R²) of EBVs

• relative weight on pedigree reduced ����less inbreeding

• genomika: Informacije na mendelejevom uzorkovanju za mlade bikove ����SNP-Markers

• Koliko puno? Veličina kalibracije, Ne, smjestajmarkera, kvaliteta(R²) EBV-a

• Smanjeni utjecaj pedigrea����manje uzgoja u srodstvu.

Uzgoj u srodstvu Inbreeding

• ‚Outcross‘: gEBV allows to test candiates with interesing pedigree even with lower parent average

• Need to genotype many candidates

• ‚Outcross‘: gEBV dopusta testiranje kandidata sa interesantnim pedigreom iako su roditelji manjeg prosjeka

• Potrebno genotipiziratimnogo zivotinja

Uzgoj u srodstvu Inbreeding

13

• GS-young sires replace proven bulls as elite sires and 2nd crop bulls

• R² levels substantially reduced: 60-70% instead >90%

• Thus larger relative weight on pedigree

• Increases inbreeding rate

• GS-mladi bikovi zamjenjuju provjerene bikove kao elitni bikovi i crop 2nd crop bikovi

• R² nivo znacajno se reducira: 60-70% umjesto >90%

• To povecava utjecaj pedigrea na UV

• Povecanje uzgoja u srodstvu

Uzgoj u srodstvu Inbreeding

• GS shortens generationinterval

• even at constant ΔF rates/gen. �larger ΔF/year

• Egger-Danner a. Willam:

base scenario 5,6 yrs.

GS 3 scenario 4,3 yrs

• +30% ΔF/year

Uzgoj u srodstvu Inbreeding

• x

14

• e.g.: ‘Runs of Homozygosity’ �long homozygous segments

Nove mjere

uzgoja u srodstvu

New Measures of

Inbreeding

• e.g.: ‘Runs of Homozygosity’ �long homozygous segments

Ge

ne

rati

on

en

Nove mjere

uzgoja u srodstvu

New Measures of

Inbreeding

15

• Ferenakovic´ et al. (2011): short ROH blocks allow to identify old inbreeding:

• inbreeding levels up to 8.5% estimated (cf. FPED=1,3%)

• breed comparison shows much shorter ROH blocks in FV as compared to BV

Nove mjere uzgoja

u srodstvu

• Maximizing genetic gain while restricting ∆∆∆∆ F

• Software - input

• selection candiates, gEBVs

• Pedigree

• Software - output

• selected candidates frequency of use, mating lists, ∆F, ∆G,

• OGC maximises long term ∆∆∆∆G

Optimum Genetic Contribution(Woolliams und Meuwissen, 93; Meuwissen , 97)

• x

16

Optimum Genetic Contribution(Woolliams und Meuwissen, 93; Meuwissen , 97)

‘conservation’ : many bulls evenly used

‘balanced’ : best bulls more heavily used

‘intensive’ : very best bulls massively used

gene

tski

napr

edak

Povecanje uzgoja u srodstvu

Optimum Genetic Contribution(Woolliams und Meuwissen, 93; Meuwissen , 97)

gene

tic G

ain

Povecanje uzgoja u srodstvu

balanced’ : best bulls more heavily used

���� Optigene

Project

lower ∆G in short term,larger ∆G in long term

17

• GS – novi alat� GS funkcionira na simentalcu, iako

nije isti R² nivo kao kod holsteina

• Ubrzava uzgoj�koji je uzgojni cilj?

�jos je u razvoju

• Uzgoj u srodstvu� Bolja kontrola, ali kraci

generacijski interval

� Neto efekt GS-a ostaje nejasan

� Treba obratiti paznju na ! (nova

molekularna mjerenja , OGC )

• GS – a new tool� GS is working in Fleckvieh,

although no same R² level as in Holstein

• Speeds up breeding�what is the breeding goal?

�Under development

• Inbreeding� better control but shorter

generation interval

� net effect of GS remains unclear

� needs to be taken care of ! (newmolecular measures, OGC)

Zakljucak Conclusions

• Genomska lavina� HD podaci 777.000 SNP po zivotinji

� Dosljedni podaci

� Pohranjivanje i statistickomodeliranje je vrlo izazovno

• Fenotip je kralj!� Svi imaju genotip

� Temeljito i jasno vodjenje podataka je kljucno za optimalnu upotrebu upotrebu genotipa

• Genomic data avalanche� HD data 777.000 SNP per animal

� Sequence data

� Storage, and statistical modeling isvery challenging

• Phenotype is King!� Everyone has genotypes

� Thorough and broad data recordingis essential for optimal use ofgenotypes

Zakljucak Conclusions

18

Gesundheitsmonitoring Rind: Vodjenje podataka o zdravlju za potrebe

vodjenja stada i uzgoj

Gesundheitsmonitoring Rind

nepromjenjeno Osrednji napredak Jak napredak

Breeding goals of breeders fromFIH breeders association

(Questionaire 1/2009 (N=700, 33% of Members), Miesenberger)

Uzgojni ciljevi uzgajivaca od FIH uzgojnih udruga

(anketa 1/2009 (700,33% clanova), Misenberger

19

Which bulls are thebreeders using? - FV Austria

Ukupni uzgojni indeks -TMI

Mlijecni index Mesni indeks Fitnes indeks

Koje bikove uzgajivacikoriste

System torecord

diagnostic data

Improve health bybreeding

Improve health by herd management

Health reportsfarmers

Health reportsveterinarians

Breeding value estimation

Project “Health Monitoringin Cattle” (2006-2010)

Ciljane grupe: Farme sa biljezenjem rezultata – volontersko sudjelovanje!

Projekt „Nadziranje zdravlja stoke” (2006-2010)

20

Diagnoses data -from receipt to data base

Veterinarien

AAA-receiptdiagnosis

diagnosis AAA-receipt - copy

Farmer Employee performance

recording organisation

manual recording

RDV-database

health reports

interfaceVET-programme

New – standardisation of diagnosis

with consent of farmer

50 % electronically transmitted

Podaci dijagnoze-od izvora do baze podataka

Standardisation ofdiagnoses

Austrian-wide code – published by theMinistry of Health in 04-2006

... on-site diagnose samo od strane veterinara...trenutno nema laboratorijskih rezultata.

Standardizacija dijagnozaAustrijski –obuhvatni kod-objavljen od starne Ministarstva

zdravstva u travnju 2006.

21

Official document on use of drugs

Podaci koji se vode:Broj farme, broj zivotinje, diagnoza

farme, datum dijagnoze, broj veterinara

Upotreba lijekova po austrijskom zakonu mora biti evidentirana!

Sluzbeni dokument o upotrebi lijkova

78

1

33

3744

55

79

76

GMON Participation % of all

farms under recordingtotal 13.191 farms

Auswertung: November 2010

GMON % sudjelovanja od

svih farmi pod kontrolom

22

•12/10: prve službene uzgojne vrijednosti za svojstva zdravlja

•svojstva:

Rani poremecaji plodnosti (0-30dana)

Cisticni jajnici (30-150 dana pp)

mastitis: -10 do 150 dana pp)

Mlijecna groznica: -10 do 10 danapp

•Svojstva zdravlja: dio su sluzbenog uzgojnog programa austrijskog simentalca, smedjeg i sivog goveda

• 12/10: first official breedingvalues on health traits

•traits:

early fertility disorders (0-30days)

cystic ovaries (30-150 days pp)

mastitis: -10 bis 150 days pp)

milk fever: -10 bis 10 days pp

•health traits: part of officialbreeding programmes in Austrian Fleckvieh, Braunvieh andGrauvieh

Genomska

procjenagenetic evaluation

Top-flop lista top-flop list

16,8

7,3

0

2

4

6

8

10

12

14

16

18

Flop-20 Top-20

Mas

titis

(%)

9,0

2,7

0

1

2

3

4

5

6

7

8

9

10

Flop-20 Top-20

früh

e F

ruch

tbar

keits

stör

unge

n (%

)

11,1

1,8

0

2

4

6

8

10

12

Flop-20 Top-20

Zys

ten

(%)

10,7

1,7

0

2

4

6

8

10

12

Flop-20 Top-20

Milc

hfie

ber (

%)

Znacajne genetske razlike izmedju bikova!

ea

rly

fe

rtil

ity

dis

ord

ers

(%

)

• diagnosticki odnos kceri od 20 vrhunskih i bikova sa zacelja liste

Flop-20 Top-20

Flop-20 Top-20Flop-20 Top-20

Flop-20 Top-20

mil

k f

ev

er(

%)

cyst

ic o

va

rie

s (%

)m

ast

itis

(%

)

23

Number of bulls with

official EBVs

0

20

40

60

80

100

120

140

160

180

200

1990 1992 1994 1996 1998 2000 2002 2004 2006

broj

Godina rodjenja

Mas

fFru

Zyst

Mifi

MA

EFD

CYS

MF

Broj bikova za

sluzbenim EBV-om

EBV correlations

MAS EFD CO MF

GZW -0,04 0,10 -0,04 -0,10

MW -0,32 0,01 -0,12 -0,25

FIT 0,36 0,22 0,14 0,09

Mkg -0,36 -0,04 -0,11 -0,26

ND 0,16 0,20 0,11 0,05

FRUm 0,24 0,16 0,22 0,06

ZZ 0,49 -0,03 0,04 0,15

DMG -0,19 -0,13 -0,13 -0,20

Euterboden 0,23 -0,03 -0,02 -0,06

EBV korelacije

06.06.2013

24

Farmamedian

Regijamedian

podrucjemedian

31.4% 13% 21%

Farma pripada doljnjoj cetvrtini farmi u tom podrucju

Dijagnosticki odnosmastitisa

Use of health data forfarm management

Upotreba podataka o zdravlju za vodjenje farme•Procjenjuje zdravstveni status stadau usporedbi sa drugim farmama u slicnim uvjetima (regija, podrucje)

•assess health status of herd relative to other farms under similar conditions (district, province)

48

Zdravstveni kartoni

Upotreba podataka o zdravlju za vodjenje farme

Use of health data forfarm management

25

• Uzgajivaci zele popraviti zdravlje krava

• Funkcionalna svojstva i svojstva zdravlja

• Kupci traze zdrave proizvode od zdravih krava

• Kvaliteta podataka je dovoljna da bi odrzala suvislost uzgojnih vrijednosti

• Redovno vodjenje podataka o zdravlju zahtjeva vece progenegrupe/bikovi su upotrebljiviji

• Breeders want to improvehealth of cows

• Health and fitness is stable but no relevant genetic gains

• Consumers ask for healthyproducts from healthy cows

• Data quality is sufficient toobtain meaningful breedingvalues

• Dense health data recordingneeded larger progenygroups/sire useful

Zakljucak Conclusions

AcknowledgementZahvala

Die Entwicklung wird in Zusammenarbeit von AT+DEU durchgeführt. Arbeitsgruppe Genomische Selektion: Vorsitz Götz (ITZ Grub)

Egger-Danner, Fürst, Mayerhofer, Schwarzenbacher

Gredler, Sölkner

Tanzler

Edel, Emmerling, Neuner (BY), + Hamann (BW)

Röhrmoser

Duda

Folgende Fördergeber unterstützen die Entwicklung der genomischen Zuchtwertschätzung in Österreich:

FFG (Österreichische Forschungsförderungsgesellschaft GmbH )

Bundesministerium für Land-, Forstwirtschaft, Umwelt u.Wasserwirtschaft

Förderverein für Biotechnologieforschung, DEU

26

• dem Bundesministerium für Land-, Forstwirtschaft, Umwelt und Wasserwirtschaft, dem Gesundheitsministerium und den Bundesländern für die finanzielle Unterstützung.

• den Projektpartnern für die wertvolle Unterstützung und gute Zusammenarbeit.

• den teilnehmenden Bauern und Tierärzten.

AcknowledgementZahvala

Lascaux Cave, France 14,000 B.C.

27

• Sequenz: 3 Mrd. Buchstaben (A,T,G,C) | Slijed

• >45 Mio. SNP bekannt |poznati

• HD-Chip

• 50K-Chip

• 3K-Chip

�1 Buchstabe / 1cm 1 Nukleotid/1 cm

���� 1 SNP / 66 cm

���� 1 SNP / 40 m

���� 1 SNP / 550 m

���� 1 SNP / 10 km

50K Bovine SNP Beadchip