Chromosomes are thread-like structures within human cells that carry our genetic blueprint. Humans typically have 23 pairs, one from each parent. These structures contain thousands of genes, which instruct the body to make proteins. Chromosome 8 is one such pair.
The Role of Chromosome 8
Chromosome 8 is an autosome, meaning it is not involved in sex determination. It is a medium-sized chromosome, spanning over 146 million base pairs, representing approximately 4.5% to 5% of the total DNA in human cells. Researchers estimate that chromosome 8 contains about 700 to less than 1,000 genes.
The genes on chromosome 8 are involved in many bodily functions. Many genes contribute to the development of body organs and play roles in psychomotor and neurocognitive development. For instance, about 8% of its genes are linked to brain development and function, while approximately 16% are associated with cancer. A notable gene on chromosome 8 is MYC, which encodes a protein that acts as a transcription factor, controlling the expression of many genes involved in cell proliferation, growth, and programmed cell death.
Numerical Abnormalities
Numerical abnormalities involve an incorrect count of entire chromosomes. Trisomy 8 is a condition where cells contain three copies of chromosome 8 instead of the usual two. Complete Trisomy 8, where every cell in the body has an extra chromosome 8, is generally not compatible with life and often results in miscarriage. However, Trisomy 8 most commonly occurs in a mosaic form, known as Mosaic Trisomy 8.
Mosaicism means that some cells in the body have the extra chromosome 8, while other cells have the typical two copies. This uncommon condition affects about 1 in 25,000 to 50,000 live births, and is more frequently observed in males. Mosaic Trisomy 8 arises from a random event during the formation of reproductive cells or early fetal development. The symptoms can vary widely, from subtle to pronounced, depending on the proportion and distribution of cells with the extra chromosome.
Individuals with Mosaic Trisomy 8 may present with distinctive facial features, such as a prominent forehead, widely spaced eyes, and an upturned nose. Other physical characteristics can include a short neck with extra skin folds, a narrow chest, and skeletal anomalies like scoliosis or absent kneecaps. Internal organ issues, such as kidney and heart abnormalities, are also frequently observed. Intellectual abilities vary, with some individuals experiencing mild to moderate intellectual disabilities, while others have typical intelligence.
Structural Abnormalities
Structural abnormalities refer to changes within the chromosome’s structure, rather than its total number. A deletion occurs when a segment of a chromosome is missing, while a duplication involves an extra copy of a chromosome segment. These alterations can lead to various genetic conditions, depending on the size and location of the affected segment.
One example of a deletion disorder involving chromosome 8 is Trichorhinophalangeal syndrome type II (TRPS II). This condition results from the loss of genetic material on the long (q) arm of chromosome 8. TRPS II is characterized by bone and joint malformations, distinctive facial features, and abnormalities of the hair, skin, teeth, and nails. The severity of symptoms can depend on the precise genes lost in the deleted segment.
Another structural change can be a duplication, where an extra copy of a region on chromosome 8 is present. For instance, 8p23.1 duplication syndrome involves a duplicated segment on the short (p) arm of chromosome 8. Other structural issues, such as inversions (a segment is reversed) or ring chromosomes (ends join to form a ring), can also occur on chromosome 8, impacting gene dosage and leading to a range of developmental and health challenges.
Association with Specific Diseases and Cancers
Beyond large-scale numerical and structural changes, specific diseases and cancers are linked to precise genetic alterations on chromosome 8. A translocation is a type of chromosomal rearrangement where a segment of one chromosome breaks off and attaches to a different chromosome. These translocations can move a gene to a new location, placing it under the control of different regulatory elements, which can lead to its abnormal activation.
A notable example is Burkitt lymphoma, an aggressive form of non-Hodgkin lymphoma. This cancer is frequently associated with a translocation involving chromosome 8 and another chromosome, most commonly chromosome 14, but sometimes chromosomes 2 or 22. This specific translocation typically moves the MYC gene from its usual location on chromosome 8 to a region near immunoglobulin genes on the other chromosome. The repositioning of the MYC gene leads to its uncontrolled expression, promoting the rapid proliferation of cancer cells.
Chromosome 8 is also home to genes associated with single-gene disorders, where a mutation in a single gene causes a condition. Werner syndrome is an inherited disorder that causes symptoms of premature aging, typically beginning in adolescence or early adulthood. This condition is caused by mutations in the WRN gene, located on chromosome 8. The WRN gene provides instructions for making a protein involved in DNA repair and replication, and its dysfunction can lead to accelerated cellular aging and an increased accumulation of DNA damage.