A karyotype is a visual representation of an individual’s complete set of chromosomes, arranged by size and shape. It allows examination of chromosome number and structure. Cystic fibrosis is a genetic disorder affecting organs like the lungs and digestive system. It arises from specific changes within a single gene, not large-scale chromosomal abnormalities. This distinction explains why different diagnostic methods are employed for each.
Understanding Karyotypes
A karyotype is created by collecting cells, often from a blood sample, amniotic fluid, or bone marrow. These cells are cultured in a laboratory to increase their quantity. A chemical halts cell division during metaphase, when chromosomes are most condensed and visible. The chromosomes are then stained with dyes, creating distinct banding patterns for identification.
The stained chromosomes are photographed under a microscope and arranged in pairs. This allows for the detection of large-scale chromosomal abnormalities. Karyotypes can identify conditions with an incorrect number of chromosomes, such as Down syndrome (trisomy 21), where an individual has an extra copy of chromosome 21. They also reveal major structural changes like large deletions, duplications, or translocations, where parts of chromosomes are missing, repeated, or swapped.
The Genetics of Cystic Fibrosis
Cystic fibrosis (CF) is an inherited disorder caused by mutations in the CFTR gene, located on chromosome 7. This gene provides instructions for making a protein that regulates the movement of salt and water in and out of cells. When mutated, the protein may not function correctly, leading to the production of thick, sticky mucus in various organs.
The genetic changes responsible for cystic fibrosis are microscopic alterations within the DNA sequence of the CFTR gene. These include small deletions of a few DNA building blocks or point mutations, where a single DNA building block is changed. Cystic fibrosis follows an autosomal recessive inheritance pattern, meaning an individual must inherit two copies of a mutated CFTR gene—one from each parent—to develop the condition. Individuals with only one mutated copy are considered carriers and do not show symptoms.
Why Karyotypes Do Not Detect Cystic Fibrosis
While cystic fibrosis is a genetic condition, its specific mutations are too small to be observed through standard karyotype analysis. Karyotypes visualize entire chromosomes and detect gross chromosomal abnormalities, such as changes involving large segments of DNA or entire chromosomes. The resolution of a karyotype identifies extra or missing chromosomes, or large rearrangements spanning millions of DNA base pairs.
The genetic alterations underlying cystic fibrosis, like the common F508del mutation, involve the deletion of just three DNA base pairs within the CFTR gene. These changes occur at the molecular level, within the DNA sequence of a single gene. A karyotype does not have the magnification or resolution to detect such minute changes. Therefore, a normal karyotype, showing all 46 chromosomes in their correct number and general structure, would not rule out cystic fibrosis.
Genetic Testing for Cystic Fibrosis
Genetic testing for cystic fibrosis employs methods that analyze DNA at a much higher resolution than a karyotype. Newborn screening programs often include a test for CF, measuring immunoreactive trypsinogen (IRT) levels in a blood sample. Elevated IRT levels suggest the need for further genetic testing to confirm a diagnosis.
Carrier screening is also available for individuals planning to have children or with a family history of CF. This screening analyzes a blood or saliva sample to identify if an individual carries one copy of a CFTR gene mutation. If both prospective parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two mutated copies and develop cystic fibrosis.
The definitive diagnosis of cystic fibrosis is confirmed through diagnostic gene sequencing. This method directly analyzes the DNA sequence of the CFTR gene to identify mutations. Laboratories use techniques like next-generation sequencing to read the entire CFTR gene, allowing for the detection of known and novel mutations. This detailed genetic analysis provides the information required for diagnosis and informs treatment strategies.