Chromosomes are thread-like structures found within the nucleus of animal and plant cells. Each chromosome consists of protein and a single molecule of deoxyribonucleic acid, or DNA, which carries the genetic instructions for an organism. Humans typically have 23 pairs of these structures, totaling 46 chromosomes, with one set inherited from each parent. Chromosome 17 is one of these pairs, and while it is not among the largest in terms of physical size, it is remarkably dense with genetic information. This chromosome carries a substantial number of genes that are fundamental to various bodily functions and overall health.
The Anatomy of Chromosome 17
Chromosome 17 is an acrocentric chromosome, meaning its centromere is located very close to one end. This positioning results in a noticeably short arm, referred to as the “p arm,” and a much longer arm, known as the “q arm.” The p arm extends from the centromere to the telomere, while the q arm extends from the centromere to its telomere.
This chromosome spans approximately 83 million base pairs. Despite its moderate length, it contains between 1,000 and 1,200 genes. This high gene count relative to its size makes chromosome 17 one of the most gene-rich chromosomes in the human genome.
Key Genes and Their Normal Functions
Chromosome 17 is home to several genes that perform normal functions. One is TP53, often called the “guardian of the genome.” This gene produces a protein that acts as a tumor suppressor, preventing tumors by regulating cell division and ensuring DNA integrity. The TP53 protein can halt the cell cycle for DNA repair, or, if damage is too severe, initiate programmed cell death (apoptosis).
The BRCA1 gene is another gene located on chromosome 17. Its primary function involves DNA repair, particularly double-strand breaks in the DNA helix. The protein produced by BRCA1 works with other proteins to form a complex that recognizes and repairs damaged DNA. This process is part of the homologous recombination pathway, which accurately restores the DNA sequence, maintaining genomic stability.
The NF1 gene resides on chromosome 17, regulating cell growth and development. This gene provides instructions for making neurofibromin, a tumor suppressor protein. Neurofibromin acts as a negative regulator of the Ras signaling pathway, a cascade of protein interactions involved in cell growth, differentiation, and survival. By controlling Ras activity, NF1 helps prevent uncontrolled cell proliferation.
Conditions Linked to Specific Gene Mutations
When genes on chromosome 17 undergo mutations, their normal functions can be disrupted, leading to inherited conditions. A TP53 gene mutation can result in Li-Fraumeni syndrome, an autosomal dominant disorder with an increased lifetime risk of developing multiple cancers. Individuals with this syndrome often develop sarcomas, breast cancer, brain tumors, adrenocortical carcinoma, and leukemia at young ages, due to impaired tumor suppression.
Mutations in the BRCA1 gene are associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Individuals inheriting a mutated BRCA1 gene face a higher lifetime risk of developing breast cancer, often at an earlier age, and ovarian cancer. There is also an increased risk for other cancers, including prostate and pancreatic cancers, as compromised DNA repair mechanisms lead to genetic errors.
Mutations in the NF1 gene cause Neurofibromatosis type 1, an autosomal dominant disorder primarily affecting the skin, nervous system, and bones. Individuals with NF1 often develop multiple café-au-lait spots, benign neurofibromas on nerves, and Lisch nodules on the iris. Uncontrolled cell growth from disrupted Ras pathway regulation contributes to these tumors and other developmental abnormalities.
Disorders from Large-Scale Structural Changes
Beyond single-gene mutations, conditions can arise from larger structural changes involving chromosome 17 segments. These changes involve either the loss of a segment (deletion) or an extra copy (duplication). These alterations affect the dosage of many genes, leading to different symptoms compared to single-gene defects.
Smith-Magenis syndrome is a deletion disorder caused by a deletion on the short arm of chromosome 17 at band 17p11.2. Individuals with Smith-Magenis syndrome present with intellectual disability, developmental delay, distinctive facial features, and behavioral challenges including self-harming behaviors and sleep disturbances. This condition results from the absence of multiple genes in the deleted segment.
Conversely, Potocki-Lupski syndrome arises from a duplication of the 17p11.2 region. Individuals with this syndrome have an extra copy of the genes in this segment. Characteristics include intellectual disability, low muscle tone (hypotonia), autism spectrum disorder features, feeding difficulties, and sleep apnea. Too many copies of these genes disrupt normal development, illustrating how both deletions and duplications of the same region can lead to distinct but serious conditions.