Chromosome 15 is one of the 23 pairs ofchromosomes inhumans. Like anyautosome, humans normally have two copies of this chromosome. Chromosome 15 spans about 99.7 millionbase pairs (the building material ofDNA) and represents between 3% and 3.5% of the total DNA incells. Chromosome 15 is an acrocentric chromosome, with a very small short arm (the "p" arm, for "petite"), which contains few protein coding genes among its 19 million base pairs. It has a larger long arm (the "q" arm) that is gene rich, spanning about 83 million base pairs.
Thehuman leukocyte antigen gene forβ2-microglobulin is found on chromosome 15, as well as the FBN1 gene, coding for both fibrillin-1 (a protein critical to the proper functioning of connective tissue), andasprosin (a small protein produced from part of the transcribed FBN1 gene mRNA), which is involved in fat metabolism.
The following are some of the gene count estimates of human chromosome 15. Because researchers use different approaches togenome annotation their predictions of thenumber of genes on each chromosome varies (for technical details, seegene prediction). Among various projects, the collaborative consensus coding sequence project (CCDS) takes an extremely conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes.[4]
ACSBG1: encodingenzyme Acyl-CoA Synthetase, Bubblegum Family, member 1
ADH1: alcohol dehydrogenase
ARHGAP11B: a human-specific gene encoding the Rho GTPase activating protein 11B, that amplifiesbasal progenitors, controls neural progenitor proliferation, and contributes toneocortex folding.
ARPIN: encoding protein Actin related protein 2/3 complex inhibitor
The following conditions are caused by mutations in chromosome 15. Two of the conditions (Angelman syndrome andPrader–Willi syndrome) involve a loss of gene activity in the same part of chromosome 15, the 15q11.2-q13.1 region. This discovery provided the first evidence in humans that somethingbeyond genes could determine how thegenes are expressed.[11]
The main characteristics of Angelman syndrome are severe intellectual disability,ataxia, lack of speech, and excessively happy demeanor. 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%)[citation needed], 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 theUBE3A 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,[citation needed] 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.
Angelman syndrome can be hereditary, as evidenced by one case where a patient became pregnant with a daughter who also had the condition.[12]
The main characteristics of this condition includepolyphagia (extreme, insatiable appetite), mild to moderate developmental delay,hypogonadism resulting in delayed to no puberty, andhypotonia. 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,[citation needed] 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 not 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. Because patients almost always have difficulty reproducing, Prader–Willi syndrome is generally not hereditary.
A specific chromosomal change called an isodicentric chromosome 15 (IDIC15) (also known by a number ofother names) 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), intellectual disability, seizures, and behavioral problems.[13] Signs and symptoms ofautism (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 developmental delays, delayed growth and development, hypotonia, and characteristic facial features.[citation needed] 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:[citation needed]
G-banding ideogram of human chromosome 15 in resolution 850 bphs. Band length in this diagram is proportional to base-pair length. This type of ideogram is generally used in genome browsers (e.g.Ensembl,UCSC Genome Browser).
G-banding patterns of human chromosome 15 in three different resolutions (400,[15] 550[16] and 850[3]). Band length in this diagram is based on the ideograms from ISCN (2013).[17] This type of ideogram represents actual relative band length observed under a microscope at the different moments during themitotic process.[18]
G-bands of human chromosome 15 in resolution 850 bphs[3]
^"Teacher's Guide".Ghost in Your Genes (season 35).Nova (TV series). October 16, 2007. Retrieved2009-09-26.The program...recounts how one scientist determined how the deletion of a key sequence of DNA on human chromosome 15 could lead to two different syndromes depending on whether the deletion originated from the mother or the father [and] explains that this was the first human evidence that something other than genes themselves could determine how genes are expressed.
^For cytogenetic banding nomenclature, see articlelocus.
^abThese values (ISCN start/stop) are based on the length of bands/ideograms from the ISCN book, An International System for Human Cytogenetic Nomenclature (2013).Arbitrary unit.
^gpos: Region which is positively stained byG banding, generallyAT-rich and gene poor;gneg: Region which is negatively stained by G banding, generallyCG-rich and gene rich;acenCentromere.var: Variable region;stalk: Stalk.
Gilbert F (1999). "Disease genes and chromosomes: disease maps of the human genome. Chromosome 15".Genet Test.3 (3):309–322.doi:10.1089/109065799316653.PMID10495933.
