G6S Point Mutation in Nubian Goats

a neurodegenerative genetic disease

What is G6S?

G6S is the name of a specific gene found in Nubian goats and their hybrids. It is responsible for the production of N-acetylglucosamine-6-sulfatase (G6S), which is an enzyme that is involved in the catabolism of heparin sulfate. There is a single nucleotide polymorphism (SNP) that results in an inability to produce G6S, resulting in an accumulation of heparin sulfate in the affected animal's lysosomes, which in turn affects other enzymatic activity within the lysosomes. (pictured: SGCH Saada Bellfry's Lady Vampress, a nationally-ranked goat who may have been a carrier)

How is G6S inherited?

G6S is a simply inherited gene with complete dominance. Homozygous dominant (AA) animals are 'unaffected/normal.' Heterozygous (Aa) animals are 'unaffected/carriers.' Homozygous recessive (aa) animals are 'affected.' This makes G6S a tricky disease to eliminate from the population, as carriers will not show any any defining characteristic, and even affected animals can pass unnoticed by an unaware breeder.

Progression of an animal (Running River Diversion) with G6S affected status

why should we care about G6S?

Symptoms of G6S deficiency

As mentioned above, G6S deficiency causes the build-up of waste materials in lysosomes. This happens mostly in the liver, but also in the brain. Therefore over time the animal will show symptoms of neurodegeneration (ataxia, lack of normal play/social behaviors) as well as general malaise due to the liver being unable to function efficiently. Such animals will often be noted as 'failure to thrive' and simply not growing or achieving the size typical of their breeding. The oldest known affected goat lived to nearly 4 years; most die or are put down around 2 years or younger.

How prevalent is this disease? Do we really need to worry about it?

Many breeders are not worried about G6S deficiency because they believe they have never had an affected animal born from their stock. While this is possible, it's also very likely that they culled or sold any affected animals before symptoms became obvious or attributed their decline to another factor. The current genotypic distribution in Nubians is as follows: 73.5% AA/normal, 25.2% Aa/carrier, and 1.3% aa/affected. While this disease is not going to cause the ruin of the breed any time soon, it is widespread.

Can we eliminate it?

It is certainly possible to eliminate G6S deficiency within a herd with careful testing and breeding. It is recommended that breeders only use normal bucks for breeding; it minimizes expense and is fairly effective at eliminating the gene if you continue to test buck kids that are produced. Using a normal buck, you will produce no affected animals even if you have carrier or affected does, and by testing buck kids produced you can identify which does are carriers/affected and cull them if you wish. Otherwise you can just ensure your replacements are normal. Many top-ranked bucks have been found to be carriers; for those who are concerned about losing their genetics, you can test your does and only breed to normal does to prevent the birth of affected animals. The more breeders who commit to this, the sooner we can eliminate this disease.

Discussion Questions

Is it really worth the potential loss of important genetics in this breed to eliminate this deficiency? What should be done about kids born affected; is it kinder to euthanize them early, or wait until they lose quality of life? The current distribution of genotypes almost perfectly matches the Hardy-Weinberg prediction, generally indicating that selection is not acting on this gene; is it possible there is a benefit to being a carrier that we haven't discovered yet?
Big image


G-6-S - A Genetic Defect and its Management - Goats & Health - GOATWORLD.COM Dagny Vidinsh

FAQs on G6S diagnostic testing - Texas A&M Veterinary Medical Diagnostic Laboratory

Deficiencies of glucosamine-6-sulfate or galactosamine-6-sulfate sulfatases are responsible for different mucopolysaccharidoses.

Di Ferrante, N; Ginsberg, L C; Donnelly, P V; Di Ferrante, D T; Caskey, C T (1978)
Science (New York, N.Y.) vol. 199 (4324) p. 79-81

Diagnosis of Caprine Mucopolysaccharidosis Type IIID by Real-Time Polymerase Chain Reaction-Based Genotyping

Clavijo, Alfonso; Sun, Feng; Sneed, Loyd(2010)
Journal of Veterinary Diagnostic Investigationvol. 22 (4) p. 622-627

2 J VET Diagn Invest 1998 10: 181 Margaret Z. Jones Heidi M. Hoard, Jeffrey R. Leipprandt, Kevin T. Cavanagh, Nancy K. Truscott, Beverly A. L. Levene, Karen H. Friderici and Determination of Genotypic Frequency of Caprine Mucopolysaccharidosis IIID

Image sources: