
Inbreeding is a frequent topic among Friesian owners. Given the breed's relatively small population size, coupled with periods of reduced genetic diversity and increased inbreeding, there has been a growing emphasis on health and inbreeding levels in recent years. The primary consequence of inbreeding is a rise in the frequency of pairing similar genes, known as homozygosity. But why can high inbreeding be detrimental to overall health, and how can it weaken the immune system? First, a quick genetics review.
Domestic horses have 64 chromosomes in each cell of their body, made up of 32 paired chromosomes. These chromosomes contain approximately 22,000 genes. A horse inherits two copies of each chromosome—one from its dam (via the egg) and the other from its sire (via the sperm). The two chromosomes that determine the horse's sex (X and Y chromosomes) are referred to as sex chromosomes. The dam and sire pass on traits or characteristics, such as coat color and blood type, to their foal through their genes. Some health conditions and diseases can also be transmitted genetically. There are three ways in which genetic health conditions and diseases occur:
A change in the gene occurs spontaneously either in the formation of the egg or sperm or at the time of conception.
A changed gene is passed on from the sire or dam to the foal, which causes a health issue at birth or later in life.
A changed gene is passed from the sire or dam to the foal, causing genetic susceptibility to a health condition or disease.

Related parents are more likely than unrelated parents to have offspring with health problems or genetic conditions. This is because the sire and dam share one or more common ancestors and, therefore, carry some of the same genetic material. In general, inbreeding leads to a decline in health performance. This is most evident in poorer reproduction rates, higher mortality rates, lower growth rates, and an increased risk of hereditary defects. Recent anecdotal reports from veterinarians indicate concerns that Friesian horses have reduced immune system function compared to other breeds. This raises a common question: even if genetic tests are created for hereditary diseases in Friesians, such as megaesophagus, gastric rupture, and aortic rupture, how will we address the long-term effects that inbreeding may have on their immune system? To explore this question, we must first examine how inbreeding affects the immune system.
The immune system plays a vital role in the health of any animal, defending against infections and protecting the body's cells. One of its most essential functions is to recognize and destroy foreign invaders like bacteria and viruses. To accomplish this, a group of genes known as the major histocompatibility complex (MHC) are critical for the recognition aspect of this process. MHC genes code for protein molecules that are constantly searching for pathogens. A useful way to imagine this is to compare it to how an enemy might be recognized on the battlefield by the color or features of their uniform. While pathogens don't wear uniforms, they do have markers on their surfaces called antigens, and each type of pathogen possesses distinct antigens. MHC molecules are crucial to the immune system's ability to recognize these antigens, identify them as foreign, and recruit specific types of white blood cells to converge, enabling those white blood cells to eliminate the pathogen.

As you might imagine, any animal might encounter an immeasurable number of potential pathogens. Unfortunately, each MHC gene only provides the immune system with the opportunity to recognize a few pathogens. This is why a robust immune system requires a large number of diverse forms of MHC genes to adequately identify pathogens. For instance, humans have hundreds of MHC genes, with some exhibiting over 400 different variants. Research is ongoing in horses and among various breeds of horses to classify their MHC genes and analyze their diversity levels.
The greater the variety in an animal's MHC genes, the greater the immune system's ability to recognize and destroy pathogens. This brings us back to inbreeding and its effects on the immune system. Inbred animals exhibit less diversity among the various forms of MHC genes due to their related parents. Consequently, their immune systems may struggle to identify certain pathogens, potentially leading to a higher incidence of health issues and disease. This phenomenon is seen in endangered species, like the highly endangered European mink, where reduced genetic diversity is associated with a weakened immune system. Moreover, research on wild populations, such as snow leopards in Mongolia, highlights that declining population numbers elevate the risk of inbreeding depression, which, in turn, affects immune responsiveness. If left unchecked long enough, inbreeding will contribute to the risk of extinction for a population.

The implications of inbreeding extend to specific immune traits. Increased genome-wide homozygosity resulting from inbreeding can lead to the emergence of harmful recessive mutations, which may suppress immune function and increase susceptibility to diseases. For instance, research on banded mongooses has shown that inbred individuals exhibited higher parasite burdens due to immune suppression. Similar effects have been observed in laboratory studies involving guppies, where inbreeding led to increased parasite infections, indicating that inbred individuals not only have heightened disease susceptibility but also slower recovery rates from infections. Furthermore, inbreeding has been linked to significant reductions in immune responses in agricultural animals, such as cattle and chickens.
Despite the adverse impacts of inbreeding on immune function, some research highlights that not all populations show immediate negative consequences linked to inbreeding. For example, in koalas, heritable genetic variance does not always equate to observable inbreeding depression. This indicates that while inbreeding generally leads to decreased immune function, other genetic factors or environmental influences may mediate the extent of these effects.
In summary, inbreeding has a significant negative impact on immune system function, primarily due to decreased genetic diversity and the resulting inbreeding depression. This results in weakened immune responses, heightened susceptibility to infections, and changes in physiological and behavioral traits. These consequences highlight the importance of preserving genetic diversity within populations to enhance immune function and overall population health.
References:
Bailey, E., & Brooks, S. (2020). Horse Genetics (3rd ed.). CABI. Retrieved from https://www.perlego.com/book/1438232/horse-genetics-pdf (Original work published 2020)
Esson, C., Skerratt, L. F., Berger, L., Malmsten, J., Strand, T., Lundkvist, Å., … & Johansson, Ö. (2019). Health and zoonotic infections of snow leopardspanthera unicain the south gobi desert of mongolia. Infection Ecology &Amp; Epidemiology, 9(1), 1604063.
Esson, C., Skerratt, L. F., Berger, L., Malmsten, J., Strand, T., Lundkvist, Å., … & Johansson, Ö. (2019). Health and zoonotic infections of snow leopardspanthera unicain the south gobi desert of mongolia. Infection Ecology &Amp; Epidemiology, 9(1), 1604063.
Mitchell, J., Vitikainen, E., Wells, D. A., Cant, M. A., & Nichols, H. J. (2016). Heterozygosity but not inbreeding coefficient predicts parasite burdens in the banded mongoose. Journal of Zoology, 302(1).
Smallbone, W., Oosterhout, C. v., & Cable, J. (2016). The effects of inbreeding on disease susceptibility: gyrodactylus Turnbull infection of guppies, Poecilia reticulata. Experimental Parasitology, 167, 32-37. https://doi.org/10.1016/j.exppara.2016.04.018.
Freem, L., Summers, K., Gheyas, A., Psifidi, A., Boulton, K., MacCallum, A., … & Hume, D. (2019). Analysis of the progeny of sibling matings reveals regulatory variation impacting the transcriptome of immune cells in commercial chickens. Frontiers in Genetics, 10.
Salim, B., Nakao, R., Chatanga, E., Marcuzzi, O., Eissawi, M. A., Almathen, F., … & Giovambattista, G. (2024). Exploring genetic diversity and variation of over-drb1 gene in Sudan desert sheep using targeted next-generation sequencing. BMC Genomics, 25(1).
Cristescu, R., Strickland, K., Schultz, A., Kruuk, L. E. B., Villiers, D. d., & Frère, C. (2022). Susceptibility to a sexually transmitted disease in a wild koala population shows heritable genetic variance but no inbreeding depression. Molecular Ecology, 31(21), 5455-5467.

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