Chromosome 15 (human)
Encyclopedia
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s in human
Human
Humans are the only living species in the Homo genus...
s. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s (the building material of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
) and represents between 3% and 3.5% of the total DNA in cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
.
Identifying gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s 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.
Genes
The following are some of the genes located on chromosome 15:- CAPN3CAPN3Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.-External links:* The MEROPS online database for peptidases and their inhibitors: ** LOVD mutation database:...
: Calpain 3 (limb-girdle muscular dystrophy type 2A) - CHPCHP (gene)Calcium binding protein P22, also known as CHP, is a human gene.-Interactions:CHP has been shown to interact with Sodium-hydrogen antiporter 1 and Sodium-hydrogen antiporter 3.-Further reading:...
: Calcium binding protein P22 - FAH: fumarylacetoacetate hydrolase (fumarylacetoacetase)
- FBN1FBN1Fibrillin-1 is a protein that in humans is encoded by the FBN1 gene.This gene encodes a member of the fibrillin family. The encoded protein is a large, extracellular matrix glycoprotein that serve as a structural component of 10-12 nm calcium-binding microfibrils...
: fibrillin 1 (Marfan syndrome) - HEXAHEXAHexosaminidase A , also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene.Hexosaminidase A and the cofactor GM2 activator protein catalyze the degradation of the GM2 gangliosides and other molecules containing terminal N-acetyl hexosamines...
: hexosaminidase A (alpha polypeptide) - IVD: isovaleryl Coenzyme A dehydrogenase
- MCPH4MicrocephalinMicrocephalin is one of six genes causing primary microcephaly when non-functional mutations exist in the homozygous state...
: microcephaly, primary autosomal recessive 4 - OCA2OCA2P protein is a protein that in humans is encoded by the OCA2 gene.OCA2 encodes the human homologue of the mouse p gene. The P protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine - a precursor of melanin...
: oculocutsexous albinism II (pink-eye dilution homolog, mouse) - RAD51RAD51RAD51 is a human gene. The protein encoded by this gene is a member of the RAD51 protein family which assist in repair of DNA double strand breaks. RAD51 family members are homologous to the bacterial RecA and yeast Rad51...
: RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) - STRCSTRCStereocilin is a protein that in humans is encoded by the STRC gene.-Further reading:...
: stereocilin - UBE3AUBE3AUbiquitin-protein ligase E3A also known as E6AP ubiquitin-protein ligase is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells...
: 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.
- SLC24A5SLC24A5Sodium/potassium/calcium exchanger 5 also known as solute carrier family 24 member 5 is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation. The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family...
: the gene responsible for at least 1/3 of the skin color differences between races, expressed in the brain and the nervous system - EYCL3 Eye color 3, BROWN - location: 15q11-q15 (note eye colour is a polygenic trait) http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227240
- EYCL2 Eye color 2,Determines the positionning of melanocytes on the iris (note eye colour is a polygenic trait)
Chromosomal conditions
The following conditions are caused by mutations in chromosome 15. Two of the conditions (Angelman syndromeAngelman syndrome
Angelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....
and Prader-Willi syndrome
Prader-Willi syndrome
Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
) involve a loss of gene activity in the same part of chromosome 15, the 15q11-q13 region. This discovery provided the first evidence in humans that something beyond genes
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
could determine how the genes are expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
.
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
UBE3A
Ubiquitin-protein ligase E3A also known as E6AP ubiquitin-protein ligase is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells...
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.
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.Prader Willi Syndrome is hereditary.
Isodicentric chromosome 15
A specific chromosomal change called an isodicentric chromosome 15 (previously called an inverted duplication 15) can affect growth and development. The patient possesses an "extra" or "marker" chromosome. 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 chromosomal conditions
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.The following diseases are some of those related to genes on chromosome 15:
- Bloom syndromeBloom syndromeBloom's syndrome , also known as Bloom–Torre–Machacek syndrome, is a rare autosomal recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's chromosomes. The condition was discovered and first described by dermatologist Dr...
- Breast cancerBreast cancerBreast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
- Isovaleric acidemiaIsovaleric acidemiaIsovaleric acidemia, also called isovaleric aciduria or isovaleric acid CoA dehydrogenase deficiency, is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine...
- Marfan syndromeMarfan syndromeMarfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....
- Nonsyndromic deafnessNonsyndromic deafnessNonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body....
- Tay-Sachs diseaseTay-Sachs diseaseTay–Sachs disease is an autosomal recessive genetic disorder...
- TyrosinemiaTyrosinemiaTyrosinemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms include liver and kidney disturbances and mental retardation...