Identifying genes on each chromosome is an active area of genetic
research. Because researchers use different approaches to predict the
number of genes on each chromosome, the estimated number of genes
varies. Chromosome 4 likely contains 1,000 to 1,100 genes that provide
instructions for making proteins. These proteins perform a variety of
different roles in the body.
Genes on chromosome 4 are among the estimated 20,000 to 25,000 total genes in the human genome.
Genes on chromosome 4 are among the estimated 20,000 to 25,000 total genes in the human genome.
How are changes in chromosome 4 related to health conditions?
Many genetic conditions are related to changes in particular genes on chromosome 4.
This list of disorders associated with genes on chromosome 4 provides links to additional information.
Changes in the structure or number of copies of a chromosome can also cause problems with health and development. The following chromosomal conditions are associated with such changes in chromosome 4.
Changes in the structure or number of copies of a chromosome can also cause problems with health and development. The following chromosomal conditions are associated with such changes in chromosome 4.
- cancers
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Changes in chromosome 4 have been identified in several types of
human cancer. These genetic changes are somatic, which means they are
acquired during a person's lifetime and are present only in certain
cells. For example, rearrangements (translocations) of genetic material
between chromosome 4 and several other chromosomes have been associated
with leukemias, which are cancers of blood-forming cells.
A specific translocation involving chromosome 4 and chromosome 14 is commonly found in multiple myeloma, which is a cancer that starts in cells of the bone marrow. The translocation, which is written as t(4;14)(p16;q32), abnormally fuses the WHSC1 gene on chromosome 4 with part of another gene on chromosome 14. The fusion of these genes overactivates WHSC1, which appears to promote the uncontrolled growth and division of cancer cells.
- facioscapulohumeral muscular dystrophy
-
Facioscapulohumeral muscular dystrophy results from a deletion of
genetic material from a region of DNA known as D4Z4. This region is
located near the end of the long (q) arm of chromosome 4 at a position
described as 4q35. The D4Z4 region normally consists of 11 to more than
100 repeated DNA segments, each of which is about 3,300 DNA base pairs
(3.3 kb) long. However, in people with facioscapulohumeral muscular
dystrophy the D4Z4 region on one copy of chromosome 4 is abnormally
short, containing between 1 and 10 repeats.
It is uncertain how a shortened D4Z4 region causes the progressive muscle weakness and wasting characteristic of facioscapulohumeral muscular dystrophy. Researchers have proposed several possible mechanisms, but none have yet been proven. It appears that the D4Z4 region influences the activity of other genes located nearby on the long arm of chromosome 4. An abnormally short D4Z4 region may somehow disrupt the normal regulation of these genes. However, it is unclear which genes are influenced by D4Z4 and what role, if any, those genes play in muscle cells. Researchers suspect that genetic factors other than the shortened D4Z4 region may also be involved in facioscapulohumeral muscular dystrophy.
- PDGFRA-associated chronic eosinophilic leukemia
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PDGFRA-associated chronic eosinophilic leukemia is caused by genetic abnormalities that involve the PDGFRA
gene, a gene found on chromosome 4. This condition is a type of blood
cell cancer characterized by an increased number of eosinophils, a type
of white blood cell involved in allergic reactions.
The PDGFRA gene abnormalities are somatic mutations, which are mutations acquired during a person's lifetime that are present only in certain cells. The most common of these abnormalities is a deletion of genetic material from chromosome 4 that removes approximately 800 DNA building blocks (nucleotides) and brings together parts of two genes, FIP1L1 and PDGFRA, creating the FIP1L1-PDGFRA fusion gene. Occasionally, through mechanisms other than deletion, genes other than FIP1L1 are fused with the PDGFRA gene. Rarely, mutations that change single DNA building blocks in the PDGFRA gene (point mutations) cause this condition.
The protein produced from the FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) has the function of the PDGFRA protein, which stimulates signaling pathways inside the cell that control many important cellular processes, such as cell growth and division (proliferation) and cell survival. Unlike the normal PDGFRA protein, however, the fusion protein is constantly turned on (constitutively activated), which means the cells are always receiving signals to proliferate. Similarly, point mutations in the PDGFRA gene can result in a constitutively activated PDGFRA protein. When the FIP1L1-PDGFRA fusion gene or point mutations in the PDGFRA gene occur in blood cell precursors, the growth of eosinophils (and occasionally other blood cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.
- Wolf-Hirschhorn syndrome
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Wolf-Hirschhorn syndrome is caused by a deletion of genetic material
near the end of the short (p) arm of chromosome 4 at a position
described as 4p16.3. The signs and symptoms of this condition are
related to the loss of multiple genes from this part of the chromosome.
The size of the deletion varies among affected individuals; studies
suggest that larger deletions tend to result in more severe intellectual
disability and physical abnormalities than smaller deletions.
The region of chromosome 4 that is deleted most often in people with Wolf-Hirschhorn syndrome is known as Wolf-Hirschhorn syndrome critical region 2 (WHSCR-2). This region contains several genes, some of which are known to play important roles in early development. A loss of these genes leads to developmental delay, a distinctive facial appearance, and other characteristic features of the condition. Scientists are working to identify additional genes at the end of the short arm of chromosome 4 that contribute to the characteristic features of Wolf-Hirschhorn syndrome.
- other chromosomal conditions
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Some deletions of genetic material from the short (p) arm of
chromosome 4 do not involve the critical region WHSCR-2. These
deletions cause signs and symptoms that are distinct from those of
Wolf-Hirschhorn syndrome, including mild intellectual disability and, in
some cases, rapid (accelerated) growth. People with this type of
deletion usually do not have seizures.
Trisomy 4 occurs when cells have three copies of chromosome 4 instead of the usual two copies. Full trisomy 4, which occurs when all of the body's cells contain an extra copy of chromosome 4, is not compatible with life. A similar but somewhat less severe condition called mosaic trisomy 4 occurs when only some of the body's cells have an extra copy of chromosome 4. The signs and symptoms of mosaic trisomy 4 vary widely and can include heart defects, abnormalities of the fingers and toes, and other birth defects. Mosaic trisomy 4 is very rare; only a few cases have been reported.
Other changes in the number or structure of chromosome 4 can have a variety of effects including delayed growth and development, intellectual disability, distinctive facial features, heart defects, and other medical problems. Changes involving chromosome 4 include an extra piece of the chromosome in each cell (partial trisomy 4), a missing segment of the chromosome in each cell (partial monosomy 4), and a circular structure called a ring chromosome 4. Ring chromosomes occur when a chromosome breaks in two places and the ends of the chromosome arms fuse together to form a circular structure.
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