Aidan Brougham-Cook
Dr. Ely
Biology 303
1 November 2012
The Implications of Genetics in Bovine Growth and Development
Of the vast number of topics in genetics currently being researched, one of the most significant
pursuits is the understanding of the fundamental mechanisms that regulate complex genetic traits. With
the use of recently developed analysis techniques such as linkage mapping and genome-wide
association studies, more quantitative trait loci (QTL) are being mapped and understood today than ever
before. Despite these advances, however, a complete understanding of complex traits has yet to be
achieved. Currently, complex traits are generally accepted as being derived from multiple genes acting
in unison to ultimately express a certain phenotype. As such, these complex traits are commonly
referred to as polygenetic. Some polygenetic traits that have captured the attention of scientists and
researchers for decades are stature and rate of growth. Stature is known to have an influence over
various predispositions and has been linked to productivity in farm animals. While commonly affected
by environmental factors, stature is highly heritable, in humans as well as animals. Stature was also one
of the first traits in cattle to be directly affected by human domestication (Karim et al. 2011). Bovine
stature and growth rates, Bovine referring to the subfamily Bovinae which includes animals such as
cattle, buffalo, bison, and kudu, are especially intriguing because having the ability to control these
phenotypes could potentially have direct real-world ramifications with beef farmers and dairy farmers
as they try to perfect their business model by acquiring cattle that are genetically predisposed to their
respective industries.
Keeping this practical application in mind, a particular group of scientists has been eagerly
researching potential causative genetic agents that affect stature. In their study of genes with potential
effects on bovine stature, Karim et al. (2011) successfully identified eight candidate quantitative trait
nucleotides (QTN) on chromosome 14, known as BTA14, that have a direct effect on bovine stature. It
was determined that these eight QTNs directly affect the expression of seven genes on BTA14. Of the
seven genes, the two most significant, as related to stature, are the PLAG1 gene and the CHCHD7 gene.
The PLAG1 gene is an oncogene that codes for a transcription factor that is expressed in large quantities
during fetal development but is down regulated after birth. PLAG1 also regulates a handful of growth
factors, such as IGF2, which is a notable determinant of body size. CHCHD7 codes for an extensively
expressed protein, but very little is known about its function. CHCHD7 has, however, been identified as a
PLAG1 fusion partner in tumors, establishing a link between the two genes (fusion genes are the hybrid
combination of two genes and are known to cause cancer). Of these two genes, PLAG1 is the most
appealing for future Bovine research because it regulates growth factors, because genome-wide
association studies in humans have mapped signals relating to height near to the PLAG1 gene, and
because PLAG1 knockout mice display dwarfism (in the absence of other symptoms)(Karim et al. 2011).
With the establishment of the PLAG1 gene as an attractive candidate for future bovine research,
a group of researchers based out of New Zealand decided to investigate the phenotypic consequences
of genetic variation within the PLAG1 gene. After phenotypic data such as daily growth rates, gross feed
efficiency, and residual feed intake were recorded for 942 Bos taurus dairy calves, Littlejohn et al. (2011)
studied the functional polymorphism, or SNP, ss319607402 on the PLAG1 gene and its effects on the
recorded phenotypic data. Daily growth rates were determined by recording the Kleiber ratio of each
animal over time, which is the daily weight gain per kilogram of body weight. Gross feed efficiency refers
to the ratio of the mean daily feed intakes to the daily growth rates, and residual feed intake is the
difference between the expected daily intake of the animal and the actual daily intake. After analysis, it
was reported that the PLAG1 ss319607402 genotype displayed a significant association with the body
weight of new-born calves, with peripubertal body weight, and with daily growth rate phenotypes; the
growth rate per calf was also found to differ by genotype. These results suggest that the variation within
the PLAG1 gene and bovine growth rates and size share a very strong association, which fuels further
implications that the PLAG1 gene may be a significant regulatory agent in various mammalian species.
Given the PLAG1 gene’s significant expression in the fetal tissues of mice and humans, these findings
suggest that the PLAG1 gene influences fetal development (Littlejohn et al. 2011). They also suggest that
the use of PLAG1 markers may allow for the selection of beef cattle with increased growth rates or dairy
cattle with reduced sizes such that farmers may benefit from cattle with appropriate predispositions
(Littlejohn et al. 2011).
It is interesting to note that Karim et al. (2011) and Littlejohn et al. (2011) are not the only
groups of scientists researching genetic influences in bovine cattle phenotypes. A study done by
Lindholm-Perry et al. (2011) used a genome-wide association marker method to identify QTLs that
affected bovine phenotypes such as average daily weight gain, average daily feed intake, and residual
feed intake. Such an analysis yielded several regions along the BTA14 chromosome that displayed
significant associations with at least one of the traits. Of these, two genes were selected as being the
most logical for further testing: the LYPLA1 gene and the TMEM68 gene. LYPLA1 has been known to
“deacylate ghrelin, a hormone involved in the regulation of appetite in the rat stomach, while TMEM68
is expressed in bovine rumen, abomasum, intestine and adipose tissue in cattle, and likely affects lipid
biosynthetic processes” (Lindholm-Perry et al. 2011). After genotyping and association analysis, five
markers were located near the TMEM68 gene, specifically between the TMEM68 gene and its
neighbouring gene XKR4. Although little is known about the XKR4 gene, it is involved in the expression of
red blood cell membrane proteins, which excluded it from initial pool of likely candidate genes.
However, a mutation on this QTN could alter its function and therefore affect the specific phenotypes in
question. These five markers that were identified displayed strong associations with average daily feed
intake and average daily weight gain in this particular cattle population. It should be noted that due to
the high linkage disequilibrium of these two genes, TMEM68 and XKR4, it cannot be determined which
genes are contributing to the average daily feed intake or the average daily weight gain specifically.
Further testing must be done with these markers before they can be considered for use in genetic
predisposition selection (Lindholm-Perry et al. 2011).
A follow up study done by Lindholm-Perry et al. (2012) later reported the identification of six
additional markers along the BTA14 chromosome that were associated with residual feed intake in the
same population of cattle as Lindholm-Perry et al. (2011). The follow up study also included more
phenotypes to assess, such as adjusted fat thickness, tenderness, and ribeye area; unfortunately these
did not produce any significant associations. The gene closest to the most significant SNP, BTB00557388, is the short chain dehydrogenase/reductase family 16C, member 5-like, but not much is
known about this gene and its function, making speculation as to the gene’s overall effect on growth
and stature difficult. This SNP showed the strongest association with residual feed intake after multiple
test corrections, demonstrating a 3.6% influence in this particular cattle population. While these results
are suggestive and have promise, further research is required before these markers can be utilized in
the genetic selection of cattle (Lindholm-Perry et al. 2012).
While the latter two studies conducted by Lindholm-Perry et al. (2011,2012) did not have as
significant results as Karim et al. (2011) or Littlejohn et al. (2011), they both approached the same topic
in different ways, and the result is a plethora of scientific data previously not known. It is now known
that the PLAG1 gene may play a significant role in bovine growth rate and stature, specifically during
infancy and pubescence. It is also known that there are several more potential markers on other genes
on the BTA14 chromosome that, with further research, may lead to the discovery of even more exciting
data. The applications of such research in the beef or dairy industry could be instrumental in changing
modern farming techniques and may give considerable insight into more green, efficient farming
methods of the future. This is a perfect example of collaboration within the scientific community that
has both produced promising results and paves the way for future work in this field.
Works Cited
Karim, L., Takeda, H., Lin , L., et. al (2011). Variants modulating the expression of a chromosome
domain encompassing plag1 influence bovine stature.Nature Genetics, 43(5), 405-413. doi:
10.1038/ng.814
Lindholm-Perry, A. K., Kuehn, L. A., Snelling, W. M., et al (2012). Genetic markers on bta14
predictive for residual feed intake in beef steers and their effects on carcass and meat quality
traits. Animal Genetics, 43(5), 599-603. doi: 10.1111/j.1365-2052.2011.02307.x
Lindholm-Perry, A. K., Kuehn, L. A., Smith, T. P. L., et. al (2011). A region on bta14 that includes
the positional candidate genes lypla1, xkr4 and tmem68 is associated with feed intake and growth
phenotypes in cattle. Animal Genetics, 43(2), 216-219. doi: 10.1111/j.1365-2052.2011.02232.x
Littlejohn, M., Grala, T., & Sanders, K. , et. al (2011). Genetic variation in plag1 associates with
early life body weight and peripubertal weight and growth in bos taurus. Animal Genetics, 43(5), 591594. doi: :10.1111/j.1365-2052.2011.02293.x