Genetics

Question 1

HCM: breeds

Answer 1

• Inherited in Maine Coon and Ragdoll
• Suggested to be inherited in Norwegian Forest Cat, Siberian, Sphynx, Bengals

Question 2

Maine coon HCM: inheritance

Answer 2

autosomal dominant

Question 3

Maine coon HCM: gene

Answer 3

• Mutation in Myosin Binding Protein C (MYBPC3) A31P
  o Cardiac sarcomeric protein
   Associated with familial HCM in Hu
  o Single base pair change → modify structure of protein → alter its ability to interact w other contractile proteins
  o Breed specific → not appear to be associated w HCM in other breeds

Question 4

Maine coon HCM: dz expression

Answer 4

o Inherited with incomplete penetrance and variable expressivity
 Not all cats w mutation will have disease or show same severity
 Homozygous are more likely to have dz and more severe form

• Not all Maine Coons with HCM have the same mutation
  o Likely to have >1 causative mutation

Question 5

Maine coon HCM: breeding

Answer 5

30% of Maine Coon tested have the mutation (WSU)
o Since high prevalence → cannot remove from breeding pool
 Could ↑ prevalence of other congenital defects/mutations
o Recommendation: careful if positive for mutation
 Remove homozygous cats
 Heterozygous should be monitored. If do not develop LVH → low dz penetrance

Question 6

Ragdoll HCM: inheritance

Answer 6

unknown

Question 7

Ragdoll HCM: mutation

Answer 7

• Mutation in Myosin Binding Protein C (MYBPC3) R820W
  o Located in different region of the gene (vs Maine Coon)
  o Breed specific

Question 8

Ragdoll HCM: dz expression

Answer 8

• Severity
  o Homozygous cats are severely affected → c/s <2yo
  o Heterozygous have mild form of dz
   Could only by pap muscle hypertrophy

Question 9

Ragdoll HCM: breeding

Answer 9

20% of Ragdolls tested have the mutation (WSU)
o Similar recommendations

Question 10

ARVC breeds

Answer 10

Boxer

Question 11

Boxer ARVC: inheritance

Answer 11

autosomal dominant with incomplete penetrance

Question 12

Boxer ARVC: gene

Answer 12

8 pair base deletion of striatin gene
o Striatin gene located in intercalated disc
 Colocalizes 3 desmosomal proteins: plakoglobin, plakophilin-2, desmoplakin
* Desmosome: helps to maintain structural integrity
o Myocytes adherence
o Withstand shear forces
 Abnormalities in desmosomal adherence → cardiomyocyte death, inflammation, fibrofatty replacement
 Involved in pathogenesis in Hu ARVC
o Chromosome 17

Question 13

Boxer ARVC: dz expression

Answer 13

o Homozygous: more severe form of dz
 ># of VPCs/24h
 Sudden death
 DCM form
o Not all dogs with striatin deletion develop the dz, variable severity (incomplete penetrance)

Question 14

Boxer ARVC: genetic testing/breeding

Answer 14

not known what % of Boxers have the mutation
o No mutation: could still develop dz since other mutations may participate
o Heterozygous dogs should be carefully evaluated for development of dz
 40-60% of dogs with this genotype will develop the dz
 Could be used for breeding with negative dog
o Homozygous dogs: removed from breeding pool

Question 15

DCM: breed

Answer 15

Doberman
Great Dane
Irish Wolfhound
Newfoundland
Portuguese Water Dog

Question 16

Doberman DCM: inheritance

Answer 16

autosomal dominant with incomplete penetrance

Question 17

Doberman DCM: gene

Answer 17

o Studied known mutations in Hu for DCM: desmin, delta-sarcoglycan, phospholamban, actin, lamin A/C, MYH7, troponin T, troponin C, CSRP3
 Not identified in Dobermans
o Pyruvate dehydrogenase kinase 4 (PDK4) gene:
 16 base pair deletion at the donor splice region of intron 10
 Regulatory role in cardiac energy metabolism
* Phosphorylation of pyruvate dehydrogenase → ↓ glucose oxidation when fatty acid oxidation is more efficient for energy production
* Fatty acid oxidation is the preferential form of E metabolism in healthy heart
 Studies: 18% of Dobermans are negative for mutation
* Not sole causative agent

Question 18

Doberman DCM: screening

Answer 18

Annual

Question 19

Doberman DCM: breeding

Answer 19

not recommended to breed affected individual

Question 20

Great Dane DCM: inheritance

Answer 20

X-linked
o Affected males are overrepresented

Question 21

Great Dane DCM: gene

Answer 21

o RNA expression of 2 cardiac transcripts: calstabin 2 and triadin
 Regulatory components of cardiac ryanodine receptor
 Alteration of cellular Ca2+ handling

Question 22

Irish Wolfhound DCM: inheritance

Answer 22

autosomal recessive with sex-specific alleles
o Male are overrepresented
o Develop dz at earlier age

Question 23

Irish Wolfhound DCM: gene

Answer 23

o Studies did not identified causative mutation
 Genetic markers on chromosome X
 Tafazzin gene, titin-cap, actin-alpha, cysteine/glycin-right protein 3, desmin, phospholamban, srcoglycan-delta, tropomodulin gene

Question 24

Newfoundland DCM: inheritance

Answer 24

autosomal dominant with incomplete penetrance
o Suggested
o No gender predisposition

Question 25

Newfoundland DCM: breeding

Answer 25

similar to doberman

Question 26

PWD DCM: inheritance

Answer 26

autosomal recessive
o Juvenile form of familial DCM
o Sudden collapse/death btw 2 and 32wks of age

Question 27

PWD gene

Answer 27

region on canine chromosome 8
o Test available through PennGen

Question 28

CVD breeds

Answer 28

CKCS
Dachshund

Question 29

CKCS CVD: inheritance

Answer 29

polygenic transmission
o Early onset of dz/high intensity murmurs in parents → more likely to have murmur

Question 30

CKCS CVD: breeding

Answer 30

ideally not breed affected dogs

Question 31

Dachshund CVD: inheritance

Answer 31

polygenic transmission
o Parental severity of dz correlated to severity
o Coat type related to presence/severity of mitral valve prolapse
 Long haired dogs had more severe dz vs short haired dogs