Humans normally possess 23 pairs of chromosomes within the nucleus of every cell, comprising 22 pairs of autosomes and one pair of sex chromosomes. Chromosome 8 belongs to the autosomal group and is considered an intermediate-sized chromosome, carrying a significant portion of the human genome. Alterations to this structure can have wide-ranging effects on human health and development.
The Genetic Inventory of Chromosome 8
Chromosome 8 spans approximately 146 million base pairs and represents about 4.5% to 5.0% of the total DNA content found in human cells. Researchers estimate that it contains between 700 and 1,000 genes, which provide instructions for making specific proteins.
The structure of this chromosome is divided by a central constriction point, called the centromere, into two arms: the shorter ‘p’ arm (for petit) and the longer ‘q’ arm. The genes distributed across these arms are involved in diverse biological processes. A notable portion of the genes on Chromosome 8 are linked to brain development and function, while others are implicated in the regulation of the immune system.
How Structural Changes Occur
The structure of Chromosome 8, like all chromosomes, can be physically altered through errors that occur during cell division or DNA repair. These alterations are collectively known as structural variations and can change the dosage or arrangement of genes. The breakage and reunion of chromosome segments are the underlying causes for these rearrangements.
One common type of structural variation is a deletion, which involves the complete loss of a segment of the chromosome. This results in the absence of the genes contained within that segment. Deletions can range in size from a few DNA base pairs to large portions of an arm, and the resulting health effects depend heavily on which specific genes are lost.
Conversely, a duplication occurs when a section of the chromosome is abnormally copied, leading to an extra set of genetic material. This causes an imbalance in the production of certain proteins. Duplications and deletions are often reciprocal outcomes of the same faulty mechanism, such as non-allelic homologous recombination (NAHR).
Other complex changes involve the reordering of existing material without necessarily changing the total amount of DNA. An inversion happens when a segment breaks away, flips 180 degrees, and re-inserts back into the same chromosome, reversing the order of the genes. A translocation is an exchange of segments between two different, non-homologous chromosomes. While inversions and balanced translocations may not cause symptoms in the carrier, they can lead to unbalanced chromosomes in the next generation.
Specific Syndromes and Associated Diseases
Alterations to Chromosome 8 are responsible for several recognizable genetic syndromes and can increase the risk for certain cancers. The severity of these conditions varies widely based on the size and location of the change.
Langer-Giedion Syndrome (LGS)
LGS, also known as Trichorhinophalangeal Syndrome Type II, is a rare condition caused by a specific deletion on the long arm of Chromosome 8 (band 8q24). This deletion involves the loss of multiple adjacent genes, including TRPS1 and EXT1, which contributes to the range of symptoms. Individuals often present with distinctive facial features, such as a bulbous nasal tip and sparse hair. Skeletal abnormalities are also characteristic, including multiple benign bony growths (exostoses), short stature, and cone-shaped ends of the finger and toe bones.
Warkany Syndrome 2 (Trisomy 8 Mosaicism)
Warkany Syndrome 2 involves an extra copy of Chromosome 8 present in only some of the body’s cells (mosaicism). This typically results from an error during early fetal development. The severity of symptoms depends on the proportion and location of the cells that carry the trisomy. Common physical findings include a prominent forehead, deep-set eyes, and various musculoskeletal anomalies, such as joint problems and deep creases on the palms and soles of the feet. While some individuals experience mild to moderate intellectual disability, others have normal cognitive development.
Cancer-Related Translocations
Chromosome 8 is frequently involved in cancer-related translocations that disrupt the regulation of gene expression. The most well-known example is the association with Burkitt lymphoma, a type of B-cell malignancy. This involves a reciprocal translocation between Chromosome 8 and a chromosome carrying an immunoglobulin gene (e.g., Chromosome 14). This rearrangement places the MYC proto-oncogene from Chromosome 8 under the control of highly active regulatory sequences, causing the MYC gene to become overactive. This leads to the uncontrolled cell growth characteristic of the cancer. Patients with Trisomy 8 Mosaicism also face an increased risk of developing blood-related cancers, such as leukemia.