Monogenetic - PowerPoint Presentation

Slide1

Monogenetic disorders and their implications for conservation breeding programs – a practical example from the Noriker horse breed

T. Druml und G. Brem 27th DAGENE Meeting 22nd to 24th April 2016

Institut für Tierzucht und

GenetikSlide2

PSSM Polysaccharide storage myopathyFirstly documented by Valberg 1992 – in 9 Quarter Horse related horsesIn 1997 PSSM firstly was diagnosed in 8

Draft horses (age 2 to 21 years) Diagnosis: 1. Histology 2. Clinical Symptoms

Quarter Horse: severe Symptoms, severe rhabdomyolysis, inability to

rise

– in

combination

with

RYR1 Gene

Warmblooded

horses

:

muscleatrophy

, back

problems

Draft

horse

:

overt

weakness

,

muscleatrophy

and

training-intoleranceSlide3

GYS1 gene mutationBased on muscle histology PSSM Type1 was associated with a point mutation in the GYS1 gene by McCue et al. in 2008Association

of the mutation with PSSM Type1 ranging from 65% to 87%Mutation was detected in a big

variety of breeds (Quarter Horse, Warmblooded horses

,

Draft

horses

,

Ponies

)

Age

of

the

mutation

is

1.200

to

1.500

years

In 2010

the

gene

test

was

patented

and

is

commercially

promoted

-

effects

on

breeding

of

endangered

horse

breeds

–

draft

horsesSlide4

Screening for the GYS1 mutation in draft horses breeds

Number GYS1 carrier/NCarrier

freq.%Quarter Horse1

22/335

6.6

Percheron

1

93/149

62.0

Belgier158/14939.0Shire Horse11/1950.5Clydesdale10/480.0Trekpaard117/2374.0Comtois170/8880.0Breton132/5163.0Haflinger29/5018.0Haflinger325/10823.0Noriker343/13033.0Cob Normand420/5338.0

Carrier

frequencies

in diverse

horse

breeds

1

McCue;

2

Schwarz et al. 2011;

3

Van der Hoven 2013;

4

Larcher

et al. 2008Slide5

GYS1 genotype frequencies NorikerIn total 2166 Noriker horses (1.649 foals; 208 breeding stallions; 309 breeding mares) were typed in 2014 for the GYS1

locusCarrier freq. ranging from 0.16 to 0.40

N0

1

2

Carriers

Bay

424

288

120160,32Chestnut434260139350,40Roan86582440,33Black535378146110,29Tobiano292360,21Leopard spotted1411192110,1616491126456670,32

Number

of

genotyped

Noriker

foals

born

in 2013

and

2014

structured

by

coat

colour

and

Gys1

genotype

and

carrier

frequencies

. Slide6

GYS1 genotype frequencies NorikerGYS1 carrier frequencies ranging from 4% to 62% in 518 breeding animals (stallions!)

N0

12

Carrier tot.

Carrier

stallions

Carrier

mares

Bay

135884160,350,380,33Chestnut99425070,580,620,54Roan3828910,260,320,21Black2021455250,280,310,26Tobiano5410,200,20-Leopard Sp.393630,08

0,04

0,17

518

343

156

19

0,44

Number

of

genotyped

Noriker

breeding

stallions

and

mares

structured

by

coat

colour

and

Gys1

genotype

and

carrier

frequencies

. Slide7

GYS1 genotype frequencies NorikerBay Chestnut Black Roan Leopard sp.

foalsmaresstallionsSlide8

GYS1 and inbreeding and gene pool01

2Bay4,92

5,124,54

Chestnut

6,05

6,34

6,81

Roan

4,70

4,434,58Black4,894,755,00Tobiano4,684,56Leopard spotted4,884,292,84Mean inbreeding structured by coat colour cohorts and GYS1 genotype for foals born in 2014

N

founders

effective

founders

effective

ancestors50%

Gene

pool

explained

by

n=

All

156010461124518Leopard spotted136636120259Chestnut335734883212Roan875811253212Bay4248161043714Black5358391154216

Gentic diversity parameters for the foal cohort of the year 2014 structured by coat colour

Inbreeding effect

Purging effectSlide9

GYS1 genotype frequencies stallions – sire linesN stallions

in %01

2Carrier frequencyDiamant

22

0,13

7

14

1

0,68

Elmar240,142130,13Schaunitz250,151960,24Nero330,20161430,52Vulkan650,38422030,3516911055770,38GYS1 genotype frequencies in 169 active

Noriker

breeding

stallions

by

sire

line

Carrier

frequenc

y

in all

breeding

stallions

(0.38 ) is higher than the overall mean (0.32) Diamant sire line 68% carriers!Elmar sire line (traditional Leopard spotted sire line) lowest carrier (13%) proportionGYS1 is mostly segregating in chestnut families involving chestnut Diamant and Nero stallionsSlide10

Genpool chestnutRGen-anteilGenan-teil kum

.NameVaterMutter

GFarbeGeb.

GYS1

1

10,05

0,10

Mailing Vulkan XI

Steindorf Vulkan XFalle-PaulaHLRF.1962-27,550,18Vogl Vulkan XINeukirchen Vulkan XEindruck-FriedaHKB.1958-36,430,24Gulden Diamant XIIIGin Diamant XIISusiHDF.1992145,340,29Bichl-Vulkan IXGrünwald Vulkan VIIICäsara-PerlHDF.1953-54,900,34Schieder Vulkan XIVScharler Vulkan XIIIElger-PerlHLIF.

1978

-

6

4,04

0,38

Engelbert Vulkan XV

Ewald Vulkan XIV

GabyHDRF.

1990

1

7

3,45

0,42

Bandit Nero XI

Band Nero X

Galosche-Lora

HF.1982 83,320,45Steindorf Vulkan XBürgler-Vulkan IXGunda-LotteHF.1953-93,150,48Stock Nero VIIBeham Nero VIDoraHLEF.1959-102,930,51Recke Vulkan XIIIReeder Vulkan XIIEpoxi-OlgaHLEF.1977

-112,440,54Schimmer Vulkan XVIISchachl Vulkan XVIBambarde-PerleHF.20002122,390,56Zimmeröd Vulkan IXGrünwald Vulkan VIIIGodula-SpiagHB.1952-132,260,58Saalhof Nero VIIIHauser Nero VIIAlmfrau-OlgaHDB.1953-142,03

0,60

Pölsen Vulkan XVIPramet Vulkan XV

Weste-PerlH

F.

2001

1

15

1,87

0,62

Gapper Diamant XIGalan Diamant XErdapfel-ZittaHF.1980-161,760,64Taxer Vulkan XVTweng Vulkan XIVMette-LoreHF.1993-171,680,66Matrei Vulkan XIVMarion Vulkan XIIIFreiburg-ElsaHF.1991-181,390,67Rauch Vulkan XVRaut Vulkan XIVEllipse-LotteHF.1985-191,330,68Falz Vulkan VIIISchrempf Vulkan VIIKristmana-FanniHLIF.1941-250,990,75Zirrus Schaunitz XVIZethos Schaunitz XVGerritHF.20010

15.2%

of

genes

from

carriersSlide11

Genpool Leopard spottedRGen-anteilGenanteil kum.

NameVaterMutter

SFarbegeb.

GYS1

1

14,58

0,15

Lohninger Vulk. XV

Ramses Vulkan XIV

Krokus-FanniHSFT.1989-210,840,25Jank Elmar XLerch Elmar IXLenore-LuziHBAT.1963-37,700,33Toni Vulkan XIZehetner Vulkan XHasena-LoniHSFT.1968-45,770,39Stef Elmar XIIIFritz Elmar XIIFrancy-FortunaHSFT.1998054,750,44Prinz Elmar XIIPeter Elmar XIVerena-MirliHSFT.1977

-

6

4,41

0,48

Glück Elmar XIII

Garant Elmar XII

Marlene-Lotte

HSFT.

1997

0

7

3,53

0,52

Hoffeldhof Vulkan XVII

Hofmarkt Vulkan XVI

Melanie

HSFT.1998083,420,55Pongau Elmar XIVPrag Elmar XIIIOphir-LauraHSFT.2002092,800,58Franz Elmar XIIIFritz Elmar XIIWiese-FanniHR.19990102,720,61LoriRat Vulkan XIIIGebrüll-LoreSSB.1986-

112,400,63Jubel Elmar XIIJan Elmar XIViolaHSFT.20000122,240,65Robin Elmar XIIJan Elmar XIBiancaHSFT.1998-142,160,67Linox Vulkan XVIILino Vulkan XVITanja VPRHSFT.20000132,16

0,69Grenzland Vulkan XIV

Grundner Vulk. XIII

HaikeH

SFT.

1994

0

15

2,00

0,71

Remus Nero XIIRaab Nero XIÖlbad-SofiHSFT.1994-161,840,73Mosser Diamant XIMuff Diamant XAline-JuttaHMK.1974-171,830,75Resopal-OlgaFreund Elmar XIIIDiskus-FloraSR.1999 Gene proportions of the most important ancestors of the Leopard spotted strainSlide12

Leopard spotted families

Chestnut

familiesSlide13

Diamant sire linie

Genealogical

Structure?High Frequency

of

GYS1

mutation

in

two

dominating branchesSlide14

Elmar sire linieSlide15

Practical implicationsCarrier frequencies are highest in chestnut horses: stallions 62%; mares 54%; foals 40%Lowest in Leopard spotted horses: stallions

8%; mares 17%; foals 16%Inbreeding effect in chestnut horsesPurging effect in Leopard spotted

horsesImbalance in use of breeding animals in chestnuts

Bottleneck

in Leopard

spotted

gene

pooleSlide16

Practical implicationsTwo aspects in the conservation breeding program:Maintainance of sire linesMaintainance of

coat coloursConcerning these requirements:Genotyping of colts selected

for breedingOnly homozygous carriers will be excluded

Heterozygous

carrieres

are

allowed – if they are needed to maintain the genealogical branchSlide17

ConclusionsIn chestnut families the frequency of the GYS1 mutation should be loweredBroading up genealogical sire

linesForcing chestnut non-carrier linesBroading the genealogies –

decreasing the inbreedingAvoiding mass selection of

one

or

a

few

impact siresSlide18

Thank you for the attention