Structural variation
Encyclopedia
Structural variation is the variation in structure of an organism's chromosome
. It consists of many kinds of variation in the genome
of one species
, and usually includes microscopic
and submicroscopic
types, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Typically a structure variation affects a sequence length about 1Kb to 3Mb, which is larger than SNPs and smaller than chromosome abnormality (though the definition have some overlapping). The definition of structural variation do not imply about the frequency or phenotypical effects. Many of structural variants are associated with genetic diseases, however more are not. Recent research about SVs indicates that SVs are more difficult to detect than SNPs. SNPs always occur in two alleles, while approximately 5% of the human genome are defined as structurally variant in the normal population, involving more than 800 independent genes.
Rapidly accumulating evidence indicates that structural variations can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
s, such as aneuploidies, marker chromosomes, gross rearrangements and variation in chromosome size. The frequency in human population is thought to be underestimated due to that some of these are not actually easy to identify. These structural abnormalities exist in 1 every 375 live births by putative information.
, deletions and duplications
. In recent studies , copy-number variations are tested on people who do not have genetic diseases, using a methods that are used for quantitative SNP genotyping. Results show that 28% of the suspected regions in the individuals actually do contain copy number variations. Also, CNVs in human genome affect more nucleotides than Single Nucleotide Polymorphism
(SNP).
It is also noteworthy that many of CNVs are not in coding regions. Because CNVs are usually caused by unequal recombination, widespread similar sequences such as LINEs and SINEs may be a common mechanism of CNV creation.
, and smaller inversions affecting idunorate 2-sulphatase (IDS) will cause Hunter syndrome
. More examples include Angelman syndrome
and Sotos syndrome
. However, recent research shows that one person can have 56 putative inversions, thus the non-disease inversion are more common than previously supposed. Also in this study its indicated that inversion breakpoints are commonly associated with segmental duplications. One 900 kb inversion in the chromosome 17 is under positive selection and are predicted to increase its frequency in European population.
In 2007, one study, new Copy-Number Variations are identified to play some role in Autism Spectrum Disorder and maybe other mental situations.
Structural variations also have its function in population genetics. Different frequency of a same variation can be used as a genetic mark to infer relationship between populations in different areas. A complete comparison between human and chimpanzee structural variation also suggested that some of these may be fixed in one species because of its adaptative function. There are also deletions related to resistance against malaria
and AIDS
. Also, some highly variable segments are thought to be caused by balancing selection, but there are also studies against this hypothesis.
. Under the page viewing a part of the genome, there are "Common Cell CNVs" and "Structural Var" which can be enabled.
On NCBI, there is a special page for structural variation. In that system, both "inner" and "outer" coordinates are shown; they are both not actual breakpoints, but surmised minimal and maximum range of sequence affectefd by the structural variation. The types are classified as insertion, loss, gain, inversion, LOH, everted, transchr and UPD.
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...
. It consists of many kinds of variation in the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of one species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
, and usually includes microscopic
Microscopic
The microscopic scale is the scale of size or length used to describe objects smaller than those that can easily be seen by the naked eye and which require a lens or microscope to see them clearly.-History:...
and submicroscopic
Submicroscopic
Submicroscopic is an English adjective used to describe particles of matter that cannot be seen under the most powerful optical microscope available. Atoms are examples of such submicroscopic particles....
types, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Typically a structure variation affects a sequence length about 1Kb to 3Mb, which is larger than SNPs and smaller than chromosome abnormality (though the definition have some overlapping). The definition of structural variation do not imply about the frequency or phenotypical effects. Many of structural variants are associated with genetic diseases, however more are not. Recent research about SVs indicates that SVs are more difficult to detect than SNPs. SNPs always occur in two alleles, while approximately 5% of the human genome are defined as structurally variant in the normal population, involving more than 800 independent genes.
Rapidly accumulating evidence indicates that structural variations can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
Microscopic structural variation
Microscopic means that it can be detected with optical microscopeOptical microscope
The optical microscope, often referred to as the "light microscope", is a type of microscope which uses visible light and a system of lenses to magnify images of small samples. Optical microscopes are the oldest design of microscope and were possibly designed in their present compound form in the...
s, such as aneuploidies, marker chromosomes, gross rearrangements and variation in chromosome size. The frequency in human population is thought to be underestimated due to that some of these are not actually easy to identify. These structural abnormalities exist in 1 every 375 live births by putative information.
Copy-number variation
Copy-number variation (CNV) is a large category of structural variation, which includes insertionsInsertion (genetics)
In genetics, an insertion is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping...
, deletions and duplications
Gene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
. In recent studies , copy-number variations are tested on people who do not have genetic diseases, using a methods that are used for quantitative SNP genotyping. Results show that 28% of the suspected regions in the individuals actually do contain copy number variations. Also, CNVs in human genome affect more nucleotides than Single Nucleotide Polymorphism
Single nucleotide polymorphism
A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
(SNP).
It is also noteworthy that many of CNVs are not in coding regions. Because CNVs are usually caused by unequal recombination, widespread similar sequences such as LINEs and SINEs may be a common mechanism of CNV creation.
Inversion
There are several inversions known which are related to human disease. For instance, recurrent 400kb inversion in factor VIII gene is a common cause of haemophilia AHaemophilia A
Haemophilia A is a deficiency in clotting factor VIII.Haemophilia A is inherited as an X-linked recessive trait, and thus occurs in males and in homozygous females. However, mild haemophilia A has been described in heterozygous females, presumably due to extremely unfavourable lyonization...
, and smaller inversions affecting idunorate 2-sulphatase (IDS) will cause Hunter syndrome
Hunter syndrome
Hunter syndrome, or mucopolysaccharidosis Type II, is a lysosomal storage disease caused by a deficient enzyme, iduronate-2-sulfatase . The syndrome is named after physician Charles A. Hunter , who first described it in 1917...
. More examples include Angelman syndrome
Angelman 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 Sotos syndrome
Sotos syndrome
Sotos syndrome is a rare genetic disorder characterized by excessive physical growth during the first 2 to 3 years of life. The disorder may be accompanied by autism mild mental retardation, delayed motor, cognitive, and social development, hypotonia , and speech impairments...
. However, recent research shows that one person can have 56 putative inversions, thus the non-disease inversion are more common than previously supposed. Also in this study its indicated that inversion breakpoints are commonly associated with segmental duplications. One 900 kb inversion in the chromosome 17 is under positive selection and are predicted to increase its frequency in European population.
Other structural variants
In addition to the most common kinds, there are also cryptic translocations and segmental uniparental disomy (UPD), among others. There are increasing reports of these variations, but are more difficult to detect than traditional variations because these variants are balanced and array-based or PCR-based methods are not able to locate them.Structural variation and phenotypes
Some genetic diseases are suspected to be caused by structural variations, but the relation is not very certain. It is not plausible to divide these variants into too classes as "normal" or "disease", because the actual output of the same variant will also vary. Also, a few of the variants are actually positively selected for (mentioned above).In 2007, one study, new Copy-Number Variations are identified to play some role in Autism Spectrum Disorder and maybe other mental situations.
Structural variations also have its function in population genetics. Different frequency of a same variation can be used as a genetic mark to infer relationship between populations in different areas. A complete comparison between human and chimpanzee structural variation also suggested that some of these may be fixed in one species because of its adaptative function. There are also deletions related to resistance against malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
and AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. Also, some highly variable segments are thought to be caused by balancing selection, but there are also studies against this hypothesis.
Database of structural variation
Some of genome browsers and bioinformatic databases have a list of structural variations in human genome with an emphasis on CNVs, and can show them in the genome browsing page. For example, UCSC Genome BrowserUCSC Genome Browser
The University of California, Santa Cruz is an up-to-date source for genome sequence data from a variety of vertebrate and invertebrate species and major model organisms, integrated with a large collection of aligned annotations...
. Under the page viewing a part of the genome, there are "Common Cell CNVs" and "Structural Var" which can be enabled.
On NCBI, there is a special page for structural variation. In that system, both "inner" and "outer" coordinates are shown; they are both not actual breakpoints, but surmised minimal and maximum range of sequence affectefd by the structural variation. The types are classified as insertion, loss, gain, inversion, LOH, everted, transchr and UPD.