test for the caprine G6S mutation?
by Dr. Christine King
What is G6S?
G6S is short for N-acetylglucosamine-6-sulfatase. It's a naturally occurring
enzyme that is involved in the normal turnover of glycosaminoglycans
(GAGs), which are large protein-sugar molecules that make up the connective
tissues throughout the body.
Turnover of molecules and cells is a normal part of healthy tissue maintenance.
Think of it like home maintenance and repair: as they wear out, old
or damaged GAGs are removed and replaced with new ones. So, G6S is one
of the handymen involved in maintaining healthy tissues.
What is the G6S mutation?
The G6S mutation is an inherited defect of the specific gene that directs
the production of G6S in cells. In goats with this genetic defect, the
normal production of G6S is stopped before it's completed, so G6S is
deficient in affected goats.
As a result of this defect, GAGs accumulate in the liver and other tissues.
They are particularly problematic in the brain. In fact, in humans with
this same defect, the main symptom is severe, progressive mental deterioration.
In other words, the G6S mutation causes a progressive neurodegenerative
disease. The first goat known to have died of it was a purebred Nubian
who died suddenly at 19 months of age, after having shown delayed motor
development (i.e. a delay in learning normal, age-appropriate movement
patterns and co-ordination) and retarded growth.
Because the defect causes a slowly progressive accumulation of GAGs,
which eventually "gum up the works," the signs of neurological deterioration
typically are subtle, slow to worsen, and easily missed or mistaken
for something else. In fact, sudden death may be the first sign noticed
in affected goats. Unfortunately, it's also the last, so it is well
worth breeders doing whatever they can to eradicate this genetic defect
from their herds.
How is it passed on?
The G6S mutation in goats seems to be confined to Nubians and their
crosses, such as Mini Nubians. It is described as a single, autosomal
recessive mutation, which means that it involves only one gene, it is
not sex-linked (i.e. it appears in both genders equally), and two copies
of the defective gene must be present in order for the animal to be
With the notable exception of the ovum (egg) and sperm, cells contain
two strands of genes (DNA), each strand inherited from one parent. So,
the buck donates one strand and the doe the other.
Because the G6S mutation is a single, autosomal recessive trait, its
inheritance pattern is a relatively simple one. The table below gives
the probabilities of passing on the defective gene to the kid with different
combinations of gene presence in the parents.
Probabilities of getting normal, carrier, or affected kids from different
pairings of bucks and does.
normal = negative for the mutated gene in both strands of DNA; normal
animals, unable to pass the defect to their offspring
carrier = only one copy of the gene (i.e. inherited from only one parent);
carrier animals appear normal but carry one copy of the gene, which
may be passed to their offspring
affected = positive for the mutated gene in both strands of DNA (i.e.
inherited a copy of the gene from both parents); affected animals will
most likely show signs of the disease as they age
It's important to understand that these are only general probabilities-the
chance of a certain outcome with any given breeding. It's never quite
as neat as that in real life.
For example, when breeding a normal (-/-) animal to a carrier (-/+),
even though the chances of getting a normal kid are 50:50, you might
get a string of carrier kids before you get a normal one; and vice versa.
In other words, if that particular pairing of buck and doe is repeated
10 times, then approximately 50% of the kids will be normal, but they
might be kids 2, 3, 6, 9, and 10 instead of kids 2, 4, 6, 8, and 10.
So, why test for the G6S mutation or buy G6S-negative goats?
There are two good reasons for testing for the G6S mutation in Nubians
and Mini Nubians or buying confirmed G6S-negative goats:
1. this genetic mutation compromises the health and shortens the life
of affected goats,
2. the defective gene can be identified with a blood test at any age,
so it's easy to identify affected and carrier animals and not use them
Buying kids or adult goats from a breeder who uses only G6S-negative
bucks and does in their breeding program means that you don't need to
have those goats tested for the G6S mutation. You're also supporting
the eradication of this genetic defect from the breed. If every breeder
tested for the G6S mutation and took care to use only G6S-negative animals
in their breeding program, this defect could become a thing of the past.
Copyright © 2013, Christine King. All rights reserved.
About the author: Dr. Christine King is an Australian veterinarian and
medical writer, now living and practicing in Winston-Salem, North Carolina.