SNP

Human Genomic Variations

Interindividual genomic variabilities in humans can be attributed to a number of factors 1. SNPs 2. Variable number tandem repeats (VNTRs), such as mini- and microsatellites; 3. Variations in transposable elements; and structural alterations, such as insertions/ deletions (indels), 4. Segmental duplications, and chromosomal inversions. 5. Large (~1 kb or larger) indels and duplications are generally termed copy number variations (CNVs), also referred to as copy number polymorphisms (CNPs) (if the frequency is 1% in a given population). Nonallelic recombination between homologous sequences is probably one mechanism underlying some of these variations.

Insertions and Deletions (Indels)

Extra base pairs may be added (insertions) or removed (deletions) from the DNA of a gene. The number can range from one to thousands. Collectively, these mutations are called indels. Indels involving one or two base pairs (or multiples of two) can have devastating consequences to the gene because translation of the gene is "frameshifted".

CNV
Most initial studies of genetic variation are concentrated on individual nucleotide sequences, investigators have also found that large-scale changes occur in many locations throughout the genome. These insertions, deletions, inversions, and duplications result in changes in the physical arrangement of genes on chromosomes. Indeed, for as long as cytogeneticists have studied chromosomes under microscopes, they have observed variations in chromosomal structure. These scientists have noted such anomalies as aneuploidy (abnormal chromosome number), translocations of material from one chromosome to another, large-scale deletions and insertions, fragile sites, and variations in the size of the Y chromosome (Feuk et al., 2006).

Clancy, S. (2008) Copy number variation. Nature Education 1(1)

Examples of CNV
The duplication of the Bar gene in Drosophila was one of the earliest structural variations to be linked to a phenotype. Seventy years ago, this variation was shown to cause the eye field of affected flies to be much narrower than that of flies with wild-type eyes (Bridges, 1936). Another example of a phenotypic link to a chromosomal anomaly, in humans, the duplication of part or all of chromosome 21 has been associated with Down syndrome. This duplication may be the result of nondisjunction or of translocation.
Clancy, S. (2008) Copy number variation. Nature Education 1(1)

 Hundreds of new variations in repetitive regions of DNA have been identified, leading researchers to believe that copy number variations (CNVs) are as important a component of genomic diversity as single nucleotide polymorphisms (SNPs). Redon et al. (2006) defined a CNV as a DNA segment of one kilobase (kb) or larger that is present at a variable copy number in comparison with a reference genome. Some CNVs have no apparent influence on phenotype, while as many as 40 others have been definitively linked with disease. Evidence also indicates that interaction with additional genetic or environmental factors may influence whether CNVs have a detectable phenotypic effect.
Clancy, S. (2008) Copy number variation. Nature Education 1(1)

 CNVs have been found in all human populations, as well as in other mammalian species (Freeman et al., 2006). Perhaps the best-defined and most widely known CNVs are the trinucleotide repeats (TNRs), which consist of three nucleotides repeating in tandem. TNRs exhibit dynamic expansion and contraction in a number of disease states, such as fragile X syndrome and Huntington's disease, with the number of repeats varying in both normal and afflicted individuals. In most cases, TNRs exhibit expansion with age.
Clancy, S. (2008) Copy number variation. Nature Education 1(1)

Genomic distribution of CNVRs

The chromosomal locations of 1,447 CNVRs are indicated by lines to either side of the ideograms. Green lines denote CNVRs associated with segmental duplications; blue lines denote CNVRs not associated with segmental duplications. The length of right-hand side lines represents the size of each CNVR. The length of left-hand side lines indicates the frequency with which a CNVR is detected (minor call frequency among 270 HapMap samples). When both platforms identify a CNVR, the maximum call frequency of the two is shown. For clarity, the dynamic range of length and frequency are log transformed (see scale bars). Clancy, S. (2008) Copy number variation. Nature Education 1(1)

SNPs
An SNP (pronounced snip ) is DNA sequence variation occurring in a single nucleotide in the genome. SNPs not only include variants that affect a single nucleotide (base) but also include single-base indels. For a variation to be considered an SNP, it must occur in at least 1% of the population.

 In the human genome, >65% of all SNPs involve CT transi on muta on. SNPs can occur in both coding and noncoding regions of genes. SNPs in the coding region may alter the characteristics of the protein while SNPs in the regulatory regions may alter the expression profile of genes. SNPs generally occur about every 1,000 bases in the genome but may occur more frequently in certain regions.

 In the human genome, SNPs that make up about 90% of all human genetic variations occur every 100300 bases along the genome. A set of linked SNPs that tend to inherit together as a unit is referred to as SNP haplotype. The extent of association of the SNPs as a haplotype is an indication of how closely associated they are, and linkage disequilibrium (LD) is a quantitative measure of such association. Higher LD values indicate greater association. Thus, SNPs that are in strong LD with disease-causing genes can be used as markers to identify the gene and track its inheritance.

 Each SNP location in the genome can have up to four versions: one for each nucleotide, A, C, G and T. A SNP and its distribution in a population might look like the image at the left. Not all single-nucleotide changes are SNPs, though. To be classified as a SNP, two or more versions of a sequence must each be present in at least one percent of the general population. SNPs occur throughout the human genome - about one in every 300 nucleotide base pairs. This translates to about 10 million SNPs within the 3billion-nucleotide human genome.

SNPs and disease-causing mutations

a SNP, the change must be present in at least one percent of the general population. No known diseasecausing mutation is this common. Second, most disease-causing mutations occur within a gene's coding or regulatory regions and affect the function of the protein encoded by the gene. Unlike mutations, SNPs are not necessarily located within genes, and they do not always affect the way a protein functions. SNPs are divided into two main categories: Linked SNPs (also called indicative SNPs) do not reside within genes and do not affect protein function. Nevertheless, they do correspond to a particular drug response or to the risk for getting a certain disease. Causative SNPs affect the way a protein functions, correlating with a disease or influencing a person's response to medication. Causative SNPs come in two forms: Coding SNPs, located within the coding region of a gene, change the amino acid sequence of the gene's protein product. Non-coding SNPs, located within the gene's regulatory sequences, change the level of gene expression and, therefore, how much RNA and protein is produced.

 Identifying, cataloging and characterizing SNPs in two main ways: Genomic approaches Functional approaches

http://snp.cshl.org/