Graphic: corner
spacer
Graphic: corner
spacer spacer
nav left edge
nav right edge
spacer

Neuroaxonal Dystrophy               NAD Test                Code 371

For: Papillon & Phalene

Clinical signs/disease description:  Neuroaxonal Dystrophy (NAD) in Papillon dogs is an early onset neurodegenerative disease that is characterized by severe axonal swelling, known as "spheroids". The affected dogs initially develop head tremor, wobbling gait, inability to stand and walk at a very young age, typically 1-4 months. The clinical signs gradually progress to cerebella ataxia, blindness and deafness, and most dogs do not survive beyond 7-8 months of age (1).

The disease was first reported in 1995 in England, and since then it has been sporadically observed in Papillon dogs worldwide.

The NAD mutation test:
A single nucleotide mutation in the PLA2G6 gene has been identified that is significantly associated with this form of Neuroaxonal Dystrophy (1).

The mutation based test for NAD is designed to detect the presence/absence of the PLA2G6 mutation and to clearly distinguish three groups of dogs corresponding to three genotypes:

NORMAL/CLEAR - homozygotes with two normal copies of the gene do not develop NAD and can only transmit the normal gene to its offspring.

CARRIERS - heterozygotes with one copy of the mutation and one copy of the normal gene do not develop NAD but they can transmit the PLA2G6 mutation to progeny.

AFFECTED - homozygotes with two copies of the mutated PLA2G6 gene develop clinical signs of NAD and they can only pass the mutated gene on to their offspring, although they usually die you and do not reproduce.

Testing and Breeding recommendations:
Neuroaxonal Dystrophy (NAD) in Papillon dogs is inherited as an autosomal recessive trait, which means that only dogs that receive two copies of the mutation (one from each parent) will develop the disease. Because of the recessive nature of the NAD inheritance, the mutation can exist in breeding lines without detection for many generations until two carriers of the mutation produce an affected pup. On average, 25% of the offspring from a mating between carriers will be affected. Due to random assortment of gametes and the relatively small litter size, the actual percentage of puppies affected with NAD produced in Carrier to Carrier mating often deviates from the expected 25%.

To avoid producing NAD-affected puppies, breeders are encouraged to test their dogs before they are bred, and to refrain from breeding two carriers to each other. The table below highlights in yellow the breedings that will NOT produce affected pups. These matings include at least one parent proven "Normal/Clear" by the OptiGen NAD test.


Expected results for breeding strategies using the
NAD test

Parent 1
Genotype

Parent 2 Genotype

Normal/Clear

Carrier

Affected

Normal/Clear

All = Normal/Clear

1/2 = Normal/Clear
1/2 = Carrier

All = Carrier

Carrier

1/2 = Normal
1/2 = Carrier

1/4 = Normal/Clear
1/2 = Carrier
1/4 = Affected

1/2 = Carrier
1/2 = Affected

Affected

All = Carrier

1/2 = Carrier
1/2 = Affected

All = Affected

 

References:

1. Tsuboi M, Watanabe M, Nibe K, Yoshimi N, Kato A, Sakaguchi M, et al. (2017) Identification of the PLA2G6 c. 1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis. PLoS ONE 12(1): e0169002.


spacer
Graphic: footer bar left
OptiGen®, LLC · Cornell Business & Technology Park · 767 Warren Road, Suite 300 · Ithaca, New York 14850
Tel: 607 257 0301 · Fax: 607 257 0353 · email: genetest@optigen.com or optigen@clarityconnect.com
Graphic: footer bar right
spacer spacer
spacer
spacer
spacer