A genetic disease is a condition that arises from alterations in an individual’s genetic material. These changes can range from subtle modifications in the DNA sequence to larger reorganizations of chromosome structures. Such genetic variations disrupt the body’s normal instructions, leading to impaired function or development.
Genetic Changes within Genes
Genes serve as precise instructions for building and operating all components of the human body, from proteins to complex cellular pathways. Small alterations within a single gene, gene mutations, can significantly disrupt these instructions. Such mutations can change the sequence of DNA nucleotides, leading to a faulty or absent protein product.
One common type of gene mutation is a point mutation, where a single nucleotide is substituted for another. This change can alter the amino acid sequence of a protein. For instance, in sickle cell anemia, a single nucleotide change in the beta-globin gene causes red blood cells to become rigid and crescent-shaped.
Other types of gene mutations include insertions and deletions, which involve the addition or removal of DNA within a gene sequence. An insertion adds extra nucleotides, while a deletion removes them, both leading to a “frameshift” in the genetic code. This shift can drastically alter the protein produced, resulting in a truncated or non-functional protein, as seen in cases of cystic fibrosis.
Genetic Changes within Chromosomes
Beyond individual genes, larger-scale changes in chromosomes, which are organized structures containing many genes, can also cause genetic diseases. Chromosomes neatly package our genetic material, and any significant alteration to their number or structure can have widespread effects on development and function. These changes often involve hundreds or thousands of genes simultaneously.
Numerical abnormalities occur when there are too many or too few chromosomes in a cell. A well-known example is Down syndrome (Trisomy 21), where an individual has three copies of chromosome 21 instead of the usual two. Other numerical abnormalities can involve sex chromosomes, such as Turner syndrome (one X chromosome) or Klinefelter syndrome (XXY).
Structural abnormalities involve rearrangements within or between chromosomes, without necessarily changing the total number of chromosomes. These can include deletions, where a segment of a chromosome is missing, or duplications, where a segment is repeated. Inversions occur when a segment of a chromosome is reversed end-to-end, while translocations involve segments breaking off and attaching to different chromosomes. Each of these structural changes can disrupt gene dosage or gene function, leading to various genetic conditions depending on the specific genes affected.
How Genetic Diseases are Inherited
Once a genetic change occurs, whether it is a mutation within a gene or a larger chromosomal alteration, it can be passed down through families. The pattern of inheritance depends on the location of the altered gene or chromosome and whether one or two copies of the change are needed to cause the disease. This transmission from parent to offspring explains how genetic diseases can recur within families.
Autosomal dominant inheritance occurs when only one copy of an altered gene on a non-sex chromosome (autosome) is sufficient to cause the disease. If a parent has the altered gene, there is a 50% chance their child will inherit it and develop the condition. Conditions like Huntington’s disease follow this pattern, where inheriting even one copy of the mutated gene leads to the disease.
Autosomal recessive inheritance requires an individual to inherit two copies of the altered gene, one from each parent, to develop the disease. Parents who each carry one copy of the altered gene are unaffected themselves, as they have a normal functional copy. There is a 25% chance with each pregnancy that their child will inherit both altered copies and be affected, as seen in conditions like cystic fibrosis.
X-linked inheritance involves genes located on the X chromosome, one of the two sex chromosomes. Since males have one X and one Y chromosome, and females have two X chromosomes, X-linked conditions often affect males more frequently and severely. If a male inherits an altered gene on his X chromosome, he will develop the condition because he lacks a second X chromosome to compensate. Females who inherit one altered X chromosome are typically carriers and may have milder symptoms or no symptoms at all.
When Multiple Factors Are Involved
Not all genetic diseases are solely caused by a single gene mutation or a clear chromosomal abnormality. Some conditions arise from a complex interplay of multiple genetic variations and environmental factors. These are often called multifactorial or complex disorders, reflecting their diverse origins. The risk for these conditions is influenced by an individual’s entire genetic makeup and their external exposures.
Environmental factors, such as lifestyle choices, diet, exposure to toxins, and even infectious agents, can interact with an individual’s genetic predispositions to influence disease development. For example, a person might inherit several genetic variations that slightly increase their risk for a certain condition. However, the disease may only manifest if they are also exposed to specific environmental triggers or adopt certain lifestyle habits. Conditions such as heart disease, type 2 diabetes, and many common cancers are considered multifactorial.