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Genetics, Immunity and Disease


Microbiologist and science writer Jason Tetro had this to say in a recent Twitter chat “… no clinical is the norm for most ‘infections’. The immune system rids the invader before onset of symptoms.” Jason was referring to the way that the human immune system, and the associated genetics, are more than capable of handling the thousands of exposures to germs that each of us has in a day. The human body is not limited to just one way of fighting a microbial invasion. Let’s look at three diseases and examine how the fight is conducted.

Each time that a bacteria or a virus is introduced into the human body, there is a race. The germ is designed to do one thing, reproduce, and its goal is to reproduce faster than the body can defend against its infection. The body, in turn, has to recognize the invader, and marshal the various defenses to prevent reproduction.


Leprosy is a disease right out of the Bible. Now called Hansen’s Disease, most may picture the sufferers as sitting along dusty foreign streets, begging, and displaying horrific disfigurements and amputations. That sad spectacle is no longer necessary since the development of a cure, a prolonged course of a three antibiotic cocktail.

The interesting thing about leprosy is that, according to the Centers for Disease Control (CDC) and other authorities, as much as 95 percent of the population is immune to the disease. In these patients, the body’s immune system is able to prevent clinical illness by defeating the infection.

WHO map showing world-wide distribution of leprosy cases in 2012

WHO map showing world-wide distribution of leprosy cases in 2012

Why is this possible? In a paper titled “On the Age of Leprosy“, published February 13, 2014, the authors examine the genome of the bacteria that cause the disease, Mycobacterium leprae and Mycobacterium lepromatosis. Their conclusion is that this illness has plagued mankind for 100,000 years or more. It is, they argue, an exclusively human disease.

Based on that theory, humans evolved while dealing with leprosy. It makes sense, then, to consider that the general immunity to clinical infection is genetic. In a paper titled “Leprosy as a Model of Immunity“, the authors note that genetic variations in just two genes affect the production of immune cells targeted at leprosy. Genetic polymorphisms are responsible for the 5 percent of the population that will develop over illness if they contract leprosy.

Sickle Cell Disease

Sickle cell disease is the name given to a number of genetic, inherited red blood cell disorders. It is not an infection but it has a curious genetic tie to one.

This disease manifests when a patient inherits a gene from both natural parents. The gene and the illness is most often found in people with a specific geographical ancestry, sub-Saharan Africa, East Asia, the eastern Mediterranean, and Latin America. Those regions are also fairly congruent with the habitat of the various species of Anopheles mosquitoes that transmit the bacteria that cause malaria.

geographic distribution of malaria

CDC map illustrating the geographic distribution of malaria

In a study titled “Protective effects of the sickle cell gene against malaria morbidity and mortality“, the authors found that patients with a sickle-cell haemoglobin (HbS) gene had a much higher degree of protection from “all-cause mortality, severe
malarial anaemia, and high-density parasitaemia.” That protection peaked about the age of 12 to 16 months, when patiets areat the greatest risk from a malaria infection.

For the hundreds of thousands of patients throughout the world that suffer the horrific pain of sickle cell disease, it may come as small consolation that they were at less risk from malaria. For patients in regions where malaria does not occur, it is no consolation at all. It is, however, another good example of how the human immune system and our genome have evolved to react to an infectious disease.

Why do we get infections?

All living things have a habitat that is ideal for their needs. Habitats are bounded by environmental conditions. Some species, like humans, can survive in a range of environments, but since billions of people do not live in the Arctic, it is clear we have our preferences. Microbes, bacteria and viruses, also have preferred habitats and those govern the species that these germs can infect.

A virus, in particular, must locate a cell that it can enter. Once inside, that virus must then take over the genetics of the host cell and turn it to reproducing more viruses. The virus, in order to infect, must invade and take over cells, to reproduce, faster than the immune system can respond. A less than ideal host cell means that the immune system has a better chance of defeating the infection before a clinical illness can occur.

West Nile Fever

The West Nile virus infects birds. The various Culex species of mosquito prefer to bite birds, and carry the virus from bird to bird. Along the way, occasionally, they bite a horse or a human. Since the virus was first identified in 1937, the New York Times reports that at least eight strains of the West Nile virus have been discovered. Not all can infect humans.

West Nile transmission cycle

CDC graphic displaying the mosquito to bird to mosquito to people West Nile transmission cycle

The CDC says that 70 to 80 percent of patients who contract an illness from the West Nile virus have no symptoms. They have a sub-clinical infection. The primary reason for this is that the virus is not as efficient in infecting humans as it is birds. The patient’s immune system easily fights off the viral infection without producing any symptoms.

At the other end of the spectrum are those patients who suffer from West Nile neuroinvasive disease. Less than one percent of all West Nile infections result in this very serious version of the illness. One study, “Epidemiology and pathogenesis of West Nile virus infection“, from 2014, noted that mortality among patients with this form of illness is about ten percent. Elderly patients are at the greatest risk of death from this disease.

Because so many patients never have symptoms, it is difficult to quantify the total number of West Nile infections. The CDC has used estimates of one to 150 and one to 250. In 2014, the CDC received reports of 1,347 cases of West Nile neuroinvasive disease and 97 deaths. This suggests between 202,000 and 337,000 total West Nile infections in that year and most of those patients never noticed.

A 2013 article in the Yale News has this to say:

The elderly and people with suppressed immune systems are most susceptible to its effects, which include fever, headache, muscle pains, and various neurological diseases such as meningitis.

It is clear that the human immune system can aggressively suppress an infection by the West Nile virus in most cases. It is also clear that patients with compromised immune systems are at greatest risk of a clinical illness, West Nile fever, and West Nile neuroinvasive disease. The key to the differences is still being explored by researchers. It seems to be that humans are a less than ideal habitat for the West Nile virus and some combination of genetics and immune response that is very rapid with respect to this virus.


Here are a few more articles about the relationship between human genetics and human illnesses.

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