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Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 100 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DNA in cells.
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 15 likely contains between 700 and 900 genes.
The following are some of the genes located on chromosome 15:
- FAH: fumarylacetoacetate hydrolase (fumarylacetoacetase)
- FBN1: fibrillin 1 (Marfan syndrome)
- HEXA: hexosaminidase A (alpha polypeptide)
- IVD: isovaleryl Coenzyme A dehydrogenase
- OCA2: oculocutaneous albinism II (pink-eye dilution homolog, mouse)
- RAD51: RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)
- STRC: stereocilin
- UBE3A: ubiquitin protein ligase E3A (human papilloma virus E6-associated protein, Angelman syndrome)
- PML: promyelocytic leukemia protein (involved in t(15,17) with RARalpha, predominant cause of acute promyelocytic leukemia.
The following diseases are some of those related to genes on chromosome 15:
- Angelman syndrome
- Breast cancer
- Isovaleric acidemia
- Marfan syndrome
- Nonsyndromic deafness
- Nonsyndromic deafness, autosomal recessive
- Prader-Willi syndrome
- Tay-Sachs disease
The following conditions are caused by changes in the structure or number of copies of chromosome 15:
- Angelman syndrome: Angelman syndrome results from a loss of gene activity in a specific part of chromosome 15, the 15q11-q13 region. This region contains a gene called UBE3A that, when mutated or absent, likely causes the characteristic features of this condition. People normally have two copies of the UBE3A gene, one from each parent. Both copies of this gene are active in many of the body's tissues. In the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. If the maternal copy is lost because of a chromosomal change or a gene mutation, a person will have no working copies of the UBE3A gene in the brain.
In most cases (about 70%), people with Angelman syndrome have a deletion in the maternal copy of chromosome 15. This chromosomal change deletes the region of chromosome 15 that includes the UBE3A gene. Because the copy of the UBE3A gene inherited from a person's father (the paternal copy) is normally inactive in the brain, a deletion in the maternal chromosome 15 results in no active copies of the UBE3A gene in the brain.
In 3% to 7% of cases, Angelman syndrome occurs when a person has two copies of the paternal chromosome 15 instead of one copy from each parent. This phenomenon is called paternal uniparental disomy (UPD). People with paternal UPD for chromosome 15 have two copies of the UBE3A gene, but they are both inherited from the father and are therefore inactive in the brain.
About 10% of Angelman syndrome cases are caused by a mutation in the UBE3A gene, and another 3% result from a defect in the DNA region that controls the activation of the UBE3A gene and other genes on the maternal copy of chromosome 15. In a small percentage of cases, Angelman syndrome may be caused by a chromosomal rearrangement called a translocation or by a mutation in a gene other than UBE3A. These genetic changes can abnormally inactivate the UBE3A gene.
- Prader-Willi syndrome: Prader-Willi syndrome is caused by the loss of active genes in a specific part of chromosome 15, the 15q11-q13 region. People normally have two copies of this chromosome in each cell, one copy from each parent. Prader-Willi syndrome occurs when the paternal copy is partly or entirely missing. Researchers are working to identify genes on chromosome 15 that are responsible for the characteristic features of Prader-Willi syndrome.
In about 70% of cases, Prader-Willi syndrome occurs when the 15q11-q13 region of the paternal chromosome 15 is deleted. The genes in this region are normally active on the paternal copy of the chromosome and are inactive on the maternal copy. Therefore, a person with a deletion in the paternal chromosome 15 will have no active genes in this region.
In about 25% of cases, a person with Prader-Willi syndrome has two maternal copies of chromosome 15 in each cell instead of one copy from each parent. This phenomenon is called maternal uniparental disomy. Because some genes are normally active only on the paternal copy of this chromosome, a person with two maternal copies of chromosome 15 will have no active copies of these genes.
In a small percentage of cases, Prader-Willi syndrome is caused by a chromosomal rearrangement called a translocation. Rarely, the condition is caused by an abnormality in the DNA region that controls the activity of genes on the paternal chromosome 15.
- Other chromosomal conditions: A specific chromosomal change called an isodicentric chromosome 15 (previously called an inverted duplication 15) can affect growth and development. This small extra chromosome is made up of genetic material from chromosome 15 that has been abnormally duplicated (copied) and attached end-to-end. In some cases, the extra chromosome is very small and has no effect on a person's health. A larger isodicentric chromosome 15 can result in weak muscle tone (hypotonia), mental retardation, seizures, and behavioral problems. Signs and symptoms of autism (a developmental disorder that affects communication and social interaction) have also been associated with the presence of an isodicentric chromosome 15.
Other changes in the number or structure of chromosome 15 can cause mental retardation, delayed growth and development, hypotonia, and characteristic facial features. These changes include an extra copy of part of chromosome 15 in each cell (partial trisomy 15) or a missing segment of the chromosome in each cell (partial monosomy 15). In some cases, several of the chromosome's DNA building blocks (nucleotides) are deleted or duplicated.
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