Understanding Genetic Disorders and Their Origins
Genetic disorders encompass a wide spectrum of conditions. Their onset is often linked to mutations in our genes. These mutations can either be present from birth, found in the DNA of sperm or egg cells, or they can develop at any stage during an individual’s life, leading to conditions like certain cancers.
Some illnesses might spontaneously emerge during one’s lifetime, like various tumors, while others can be the result of inherited vulnerabilities from our parents. Depending on several external factors, these inherited predispositions might lead to a disease or remain dormant. Sometimes, parents can directly pass down a genetic condition to their children.
There’s a subset of genetic disorders, deemed „rare“, which are exceptionally uncommon in the population. A „rare“ disease is defined as one affecting less than 5 in every 10,000 people globally. There are over 6,000 identified rare diseases, including the likes of Duchenne muscular dystrophy, Spinal muscular atrophy, Rett syndrome, and Angelman syndrome. In aggregate, this equates to a significant number of patients. For perspective, in the Czech Republic alone, about half a million individuals suffer from a rare genetic disorder.
Chromosomal Level Disorders
A healthy individual typically has 23 pairs of chromosomes. However, when there’s a change in this count, it generally leads to health complications. One of the most prevalent genetic disorders of this kind is Down syndrome. During embryonic development, an extra, third copy of chromosome 21 appears during cell division. This results in varying degrees of cognitive developmental delay, shorter stature, among other symptoms.
In the given illustration, we see the arranged chromosomes, known as a human karyotype, showcasing this additional 21st chromosome. This particular karyotype belongs to a female, evident from the presence of two X chromosomes. Another illustration presents a male’s karyotype (indicated by the XY chromosome combination), but with an additional 18th chromosome. This condition leads to Edwards syndrome, characterized by severe psychomotor delays and developmental abnormalities in various organs.
By studying these karyotypes, we can not only identify additional but also missing chromosomes or parts of them. Sometimes, segments of DNA may also be found misplaced, indicating structural rearrangements.
On the left: Down syndrome with an extra 21st chromosome.
On the right: Edwards syndrome with an extra 18th chromosome.
Did you know?
Several conditions arise due to a variation in the number of chromosomes:
- Turner Syndrome – This condition occurs when there’s a loss of one X chromosome in females. Intriguingly, it’s perhaps the only disorder where an entire chromosome is missing, yet the affected individuals can live for a long time.
- Klinefelter Syndrome – Men with this syndrome have an extra X chromosome.
- Patau Syndrome – There’s an additional 13th chromosome present in individuals with this condition.
Nuclear DNA Level
Errors can also arise directly within the DNA housed in the nucleus. For instance, several nucleotides—or ‚letters’—might be missing (known as „deletions“), added (termed „insertions“), or a single nucleotide might be swapped out. This results in a mutation, causing the gene to become either entirely non-functional or to operate incorrectly.
A classic example is the mutation of the gene responsible for producing the protein hemoglobin. This mutation leads to Sickle Cell Anemia. In this situation, hemoglobin is constructed based on a flawed DNA blueprint. Consequently, red blood cells, which use hemoglobin, adopt an altered shape and exhibit compromised characteristics. This primarily manifests as restricted blood flow, leading over time to gradual organ damage. The average lifespan of individuals afflicted by this disease ranges from 40 to 60 years. Overall, around 4.5 million people globally are diagnosed with this condition, with the majority hailing from Africa. Additionally, over 40 million people are carriers, having inherited only one allele of this disease from their parents.
Mitochondrial DNA Level
Although mitochondria contain only a few coding genes, mutations based on principles similar to those in nuclear DNA are highly perilous and often fatal.
A rare genetic disease resulting from mutations in mitochondrial DNA is, for instance, maternally inherited deafness or various metabolic disorders.
