By Elizabeth Guerrero
During the mid-1800s, English scientist Francis Galton first coined the phrase ‘nature versus nurture’. The idea arose amid various questions regarding the origins of disease. In the past, societies had looked to supernatural and religious sources to explain plagues and pandemics. Later on, scientists developed new tools to observe the natural world. Over time, it was understood that modifications in the genes with which we are born, in other words mutations in the DNA sequences that make up our being, are largely responsible for the diseases we are susceptible to. Beginning in the mid-20th century, with the help of detailed scientific studies, there was the opportunity to generate more information regarding the subject. Such was the case for a study done in 2019 by Harvard University and the University of Queensland in Australia to better understand the importance of genetics in the health of 56,396 pairs of twins. The study found that 225 out of 560 diseases studied had significant levels of genetic heritability (nearly 40%). This supported the quickly progressive theory concerning the genetic, rather than environmental, basis of disease. By then, genetic disorders had been categorized into two distinct groups, complex and single-gene. The difference comes from the way in which the genetic disorders form and the impact they have on a person’s wellbeing.
Complex genetic disorders, otherwise known as multifactorial disorders, are the result of both gene mutations and external factors. Despite any genetic disposition to medical conditions, contributing factors such as exposure to dangerous chemicals as well as certain diets and medications may lead to a higher chance of developing disease. Multifactorial disorders tend to run in families and affect one sex more than the other. Affected individuals display very distinct epigenomes. Smokers, for example, can present with changes in the aryl hydrocarbon receptor repressor (AHRR) gene. The AHRR gene is important in the metabolism of xenobiotic particles such as cigarette components. Its position on chromosome 5 has led scientists to suspect its role in suppressing tumor genes. As there is a greater chance of the gene becoming modified in a smoker’s genome, these individuals will become more likely to develop cancers. AHRR modification (a form of methylation) will function alongside the most common tumor suppressor gene mutation associated with cancer, tumor protein P53. DNA alteration occurs with more ease when genetic and health-related factors work hand in hand to weaken an immune system.
When compared to the multiplex world of multifactorial disorders, single-gene genetic disorders may seem small. Also known as monogenic disorders, single-gene disorders present an alternative threat. Monogenic disorders are the result of a single gene mutation. For this exact reason they are more likely to be spontaneous occurrences, popping up in individuals who lack any familial relation to the disease. A more common, inherited single-gene disorder, cystic fibrosis (CF), is the result of a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with the mutation experience the symptoms associated with a dysfunctional CFTR protein. Mucus in the lungs becomes thicker, clogging airways and rendering the individual more prone to germs. Another organ, the pancreas, is also affected by the buildup in mucus which prevents the release of key digestive enzymes important to the proper growth of an individual. Its characterization as a monogenic disorder means there is a lack of foundational lifestyle changes that people with CF can rely on to treat their condition. Instead, individuals must seek help from mucus-thinning medications and special devices to help rid the lungs of excess mucus.
Genetic disorders, whether they be complex or single-gene, have the potential to cause severe health problems during a person’s lifetime. Though there is a significant distinction in the genetic foundation of either disorder type, both depend heavily on modifications within the DNA sequences of the affected individual. Understanding what separates single-gene from complex genetic disorders is the first step towards favorable treatment options.
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