For those who have been scrolling
through social media and various agriculture-based news outlets in the past 12
to 18 months, it may seem as though there has been quite a few “new” genetic
mutations or defects that have been identified. For most producers this is
something they have dealt with before. But for others this may be the first
time they are being faced with what seems like a “sky is falling” predicament.
Regardless of which group you belong to, understanding what genetic mutations
are, how they happen, and what to do when they are identified may prove helpful
for the future.
To put this
into perspective, cattle have 30 pairs of chromosomes. They inherit one of each
pair from their sire and the other from their dam. A typical cattle genome
consists of 2.7 billion nucleotides (A, T, G, C), or pieces of DNA, each
occurring again in a pair. When they come together to form a fertilized egg, or
future fetus, that is 5.4 billion nucleotides that are replicated each time a
cell splits and divides into another. How often do you think this occurs
perfectly? The answer is never.
When one of these base pairs is replicated
as a “mistake” it is called a mutation. While there are mechanisms in place that
look for and repair these replication mistakes, they sometimes still slip
through the error checking process. The good news is that to be passed to the
next generation, these mutations must occur in cells that form part of
reproductive tissue and could appear in the sperm or egg of a reproducing
animal. Scientists estimate that these inherited mutations occur approximately
63 times in every mating [1].
There are lots of ways these mutations arise, most of which have no actual
repercussions on the performance of an animal. The most common mutation occurs
when one nucleotide accidently replicates as another, called a nucleotide
substitution [1].
This is shown in Figure 1a where the G nucleotide has been exchanged for
an A. The second and third are called ‘insertions’ where nucleotides are added
to the DNA (Figure 1b), or ‘deletions’ where nucleotides are removed (Figure
1c).
Figure 1. Visual representations of how genetic
mutations occur in DNA via nucleotide substitution, insertion, and deletion.
The moral of the story is that mutations happen in every
living thing, and they happen relatively frequently. For easy math, in a herd
of 100 cows, there are 6,300 genetic mutations that appear in each calf crop,
not including the ones that were inherited from the generation before.
Now, you
may be asking yourself “then why don’t we see more problems in cattle than we
currently do?”. The answer is that not all mutations or changes to the DNA occur
in genes that control performance of the animal. Furthermore, a mutation in one
copy of the chromosome may be hidden by a functional copy in the other – a
common occurrence with recessive, or hidden, DNA variants where an animal must
have two copies of a gene to phenotypically express a trait. The easiest example
of this would be coat color. The calf must inherit one red variant from the
sire and another from the dam to be phenotypically red, otherwise it is just a black
hided animal who carries a single hidden red gene.
Because cattle
often need two copies of the mutation for producers to see any performance
differences, new deleterious mutations (also commonly termed genetic defects),
often go unnoticed for generations. Think of it this way, if the new mutation
occurs in a terminal animal, it is not reproduced or passed to the next
generation. Similarly, if it occurs in a registered bull that is sold to a
commercial operation, it is likely to only be passed to replacement females in
that herd who are not bred back to that same bull, and therefore never seen. The
most likely source of proliferation among a breed is when an influential AI
sire passes the mutation on multiple times in his life. Using Figure 2
as an example, an AI sire would be expected to pass down a new mutation to 50%
of his offspring. When used heavily, that could result in a lot of carriers
within a population in a relatively short period. However, the reason it goes
undetected for so long is that it takes quite a few generations for a carrier
to be mated back to a carrier and even when they are, the resulting calf would
only inherit both copies of the mutation 25% of the time. By the time the
performance issues are discovered and reported in enough quantity to merit
further investigation, the frequency of the “new” mutation has risen to a
moderate frequency through carriers.
Figure 2. An illustration of how a single genetic
mutation is propagated among a population of animals.
By now
you’ve likely realized that there is a reason this article is titled “What,
How, and When” instead of “What, How, and If”. Due to basic biology, the
occurrence of genetic mutations is not a matter of “if”, but “when”. But what
some people fail to realize is that while the word mutation has a negative
connotation, there are a lot of genetic mutations that the cattle industry
selects for. There are 8 different genetic mutations linked to the Myostatin
gene, also known as double muscling. Genetic evaluations use nucleotide
substitutions, also referred to as single nucleotide polymorphisms (SNP), to
predict breeding values for economically relevant traits like weaning weight,
marbling, and fertility. In fact, there would be no genetic progress if beneficial
mutations did not occur in the history of a population. There are a lot of ways
that these mutations work in our favor, it’s just not a lot of fun when they
don’t.
The good
news is that with the current state of DNA testing in cattle and the
commonplace practice it has become, it is a lot easier to get out in front of a
new genetic defect or mutation than it used to be. Prior to genomic technology,
the only way to confirm a sire was a carrier of a mutation was to progeny test,
and the only way to speed up that process was to mate him to his own daughters –
which took time. Today, knowing the pedigree of an animal combined with inexpensive
whole genome sequencing make it easier to identify new causal mutations that
result in genetic defects than in years before. Once identified, the SNP are
then added to current genomic testing solutions, if not present already, so
that they can be commercially available for producers to identify whether the
mutation is present in their herd or not. Once carrier animals have been
identified, mating them to animals who are free of the mutation will decrease its
frequency over time, until it is eventually all but eradicated from the
population. A practice that was not possible until genomic technology became
available.
If you learn
only one thing from this article, I hope it is this: Genetic mutations are
normal and expected. Just because a new genetic defect appears in your
population of cattle does not mean that all carrier animals are no longer
genetically relevant. There are 5.4 billion nucleotides in an animal’s genetic
makeup, to cull based on 1 of those nucleotides will not serve you, or the
breed, well moving forward. Using technology to identify carrier animals and selectively
breed out the mutation is an effective solution.
1. Harland,
C., et al., Frequency of mosaicism points
towards mutation-prone early cleavage cell divisions in cattle. BioRxiv,
2016: p. 079863.
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