Why does polymorphism occur

Called a single nucleotide polymorphism, or SNP pronounced snip , scientists are studying how SNPs in the human genome correlate with disease, drug response, and other phenotypes.

Polymorphism, by strict definitions which hardly anybody pays attention to anymore, is a place in the DNA sequence where there is variation, and the less common variant is present in at least one percent of the people of who you test.

That is to distinguish, therefore, polymorphism from a rare variant that might occur in only one in 1, people. A polymorphism, it has to occur in at least one in people. Polymorphisms could be not just single-letter changes like a C instead of T. As of October , over one million SNPs had been identified across the human genome. These copy number polymorphisms are large thousands of base pairs duplications or deletions that are found in some people but not in others.

On average, one person differs from another by 11 of these. One or more have been found on most chromosomes, and the list is probably incomplete. While most of this DNA is non-coding, functional genes are embedded in some of it. Example: AMY1 , the gene encoding salivary amylase, an enzyme that digests starch. Humans vary in the number of copies of AMY1 in their genome. In the case of AMY1 , the more copies present, the more enzyme that is produced.

How a person adapts to a change in gene number for autosomal genes is unknown in contrast to the way that human females adjust the activity of the genes on their two X chromosomes to match that of males with their solitary X chromosome. Polymorphism analysis is in widespread use. In tissue typing, it is use to find the best match between the donor, e. It is used to find disease genes e.

In population studies, it is used to assess the degree of genetic diversity in a population, including:. They arise by mutation. But what keeps them in the population? Several factors may maintain polymorphism in a population.

Eventually the entire population may become homozygous for the allele or - equally likely - the allele may disappear. Before either of these fates occurs, the allele represents a polymorphism. Two examples of reduced polymorphism because of genetic drift:. The varying number of copies of the AMY1 gene in different human populations appears to have arisen from the evolutionary pressure of the differences in the starch content of their diet.

In regions of the world e. This is because children who inherit one gene for the "normal" beta chain of hemoglobin and one sickle gene are more likely to survive than either homozygote. Children homozygous for the sickle allele die young from sickle-cell disease but children homozygous for the "normal" beta chain are more susceptible to illness and death from falciparum malaria than are heterozygotes.

Hence the relatively high frequency of the allele in malarial regions. When natural selection favors heterozygotes over both homozygotes, the result is balanced polymorphism. It accounts for the persistence of an allele even though it is deleterious when homozygous. All human populations are polymorphic for the prion protein PrP C.

It is encoded by the prion protein gene PRNP. Two of the alleles have different codons at position - one encoding methionine ; the other valine. Homozygosity for either allele increases the susceptibility to prion diseases. People who are heterozygous are more resistant. A study of elderly women who had survived the kuru epidemic of the first half of the 20th century eating the tissues of the deceased was banned in showed that This table compares the gene frequencies in this population as well as in a population that never practiced mortuary feasts.

A quick calculation will show that the gene pool of the exposed women deviates widely from what would be found if the population were in Hardy-Weinberg equilibrium. In this case, strong mortality selection is the cause.

The mass of the primer indicates SNP, and the mass difference between primer and its extension product s tells identity of incorporated nucleotide s and the genotype. This increases mass difference between extension products of alleles of a SNP, when compared with regular ddNTPs, increasing the accuracy of genotyping. This excludes excess primers from the mass spectrum, permitting the analysis of more products at the same time [ 29 ].

Monitoring fluorescence signal is widely used in genotyping technologies because its operation is simple and detection is fast with high sensitivity. Fluorescence detection is used for direct sequencing DS using capillary array electrophoresis. Fluorescence polarization FP -based detection uses the change in polarization of plane polarized light by a fluorescent dye molecule owing to change in its molecular weight under conditions of constant temperature and solvent viscosity [ 46 ].

It is well suited for low-to-medium throughput genotyping applications but is currently limited to genotyping of one SNP per assay. Chemiluminescence has several advantages as a detection technique, such as high signal-to-noise ratio, rapid detection, and feasibility for automation. The single-stranded DNA molecules which differ at a single base run on a nondenaturing gel electrophoresis display different mobility based on their native conformations Figure 9 [ 49 ].

At some point during this process, the melting temperature of the amplicon is reached and the two strands of DNA separate. This can visualize the melting behavior of the product through a fluorescent dye [ 50 ].

The fluorescent dye binds to double-strand DNA during the amplification resulting in an increase of fluorescence Figure This method is simple, cost-effective, fast and able to accurately genotype many samples rapidly. It also reduces the need to design multiple pairs of primers or purchase expensive probes. The analysis begins with a PCR amplification, followed by a step of denaturation-renaturation to create hetero-and homoduplexes from the two populations in the PCR.

The heteroduplexes with mismatch pairing and homoduplex can be detected on reversed-phase chromatography of denaturing high performance liquid chromatography DHPLC. The heteroduplexes thermally that less stable than their corresponding homoduplexes will be resolved by chromatography when subjected to a sufficiently high temperature. This mismatch will decrease the interaction with the column and a reduced retention time compared to the homoduplexes Figure Most SNPs are not responsible for a disease state.

They serve as biological markers for pinpointing a disease on the human genome map. SNPs occur on average once every base pairs [ 18 , 51 , 52 , 53 ] in the human genome. Most SNPs do not occur in the coding region of genes or even in genes [ 4 ]. Nonsynonymous SNPs that suspect in causing a human disease do not account for all SNPs that can cause disease or susceptibility to disease. Other functional SNPs associated with human disease or susceptibility to disease includes SNPs located in promoters [ 54 , 55 ], introns [ 56 ], splice sites [ 57 ], and intragenic region [ 56 , 58 ].

Even synonymous SNPs have been involved in functional consequences via unknown mechanism [ 59 ]. Variants of genes encoding drug metabolizing enzymes or drug targets have been studied in association with personal drug responses. SNPs are popular molecular markers in such pharmacogenomics studies. SNPs may be associated with the absorbance and clearance of therapeutic agents.

The association of different SNPs with a wide range of human diseases such as cancer, infectious diseases autoimmune, neuropsychiatric and others can be used as targets for drug therapy [ 60 ]. Cancer is a disease that involves abnormal cell growth. There are several kinds of cancers.

Gemignani et al. They genotyped seven SNPs of DRD2 in case and control samples and found three of the seven SNPs to be highly associated with colorectal cancer, related to reduced levels of D2 dopamine receptor. Hartikainen et al. Ribas et al. They found that allele frequencies and haplotype distributions obtained in the study were consistent with the HapMap data [ 63 ].

Shatalova et al. They found only UGT1A1 gene to be associated with risk of breast cancer. Copson et al. Arinami et al.

They found a strong association of schizophrenia to the region 1pp13 and implied that schizophrenia might have common susceptibility loci across populations with different ethnicity-specific effects. Panichareon B et al. It is a major risk factor of coronary heart disease and atherosclerosis. Thongket et al. Diabetes mellitus DM is a group of metabolic disorders. Untreated diabetes patient can cause many complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death [ 70 ].

Altshuler et al. It was found that only Pro12Ala showed a significant association with decreased risk of type 2 diabetes [ 72 ]. Polymorphism is a variation in DNA sequence that may affect individual phenotypes. The majority of variation is single nucleotide polymorphism SNP which is a single base change in a DNA sequence that occurs at a specific position in the genome.

SNP may locate within coding, or non-coding, or intergenic regions of genes. Most of SNPs have two alleles, for an individual SNP, one is major allele and the other is the minor allele based on their observed frequency in the general population. Genome-wide association studies GWAS search for SNPs that occur more frequently in person with a particular disease than in person without the disease and pinpoint genes that may contribute to risk of disease.

Linkage disequilibrium LD is commonly used to indicate that two or more genes are physically linked. It plays an important role in health and disease.

Most SNPs are not responsible for a disease state but serve as biological markers for various complex diseases such as cancer, diabetes, dyslipidemia, schizophrenia, and so on. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. Edited by Yamin Liu. Edited by Theophile Theophanides.

We are IntechOpen, the world's leading publisher of Open Access books. Built by scientists, for scientists. Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Abstract Polymorphism or variation in DNA sequence can affect individual phenotypes such as color of skin or eyes, susceptible to diseases, and respond to drug, vaccine, chemical, and pathogen.

Keywords drug development genome-wide association studies human diseases polymorphisms single nucleotide polymorphism SNPs. Introduction Phenotype of living organism is controlled by DNA.

Single nucleotide polymorphism SNP or snip SNPs are popular molecular genetic markers in disease genetics studies and pharmacogenomic research. Types of SNPs As described earlier, the SNPs may fall within coding sequences of gene, or non-coding regions of gene, or in the intergenic regions regions between genes.