DNA Polymorphisms: Definition and Overview
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DNA polymorphism refers to the existence of two or more variations (alleles) of a particular DNA sequence in a population. These variations can occur at specific positions in the genome and can be inherited. DNA polymorphisms contribute to genetic diversity within populations and can influence traits such as disease susceptibility, drug response, and physical characteristics.
Polymorphisms can occur in both coding (genes) and non-coding regions of DNA, and they can manifest as changes in nucleotide sequences, repeat numbers, or structural variations. These variations are classified into different types based on their nature and location in the genome.
Different Forms of DNA Polymorphisms
- Single Nucleotide Polymorphisms (SNPs)
- Definition: SNPs are the most common type of DNA polymorphism. They involve a change in a single nucleotide base pair at a particular position in the genome. SNPs can occur in both coding and non-coding regions of DNA.
- Types:
- Synonymous SNPs: No change in the amino acid sequence of the protein due to the mutation (silent mutations).
- Non-synonymous SNPs: A change in the amino acid sequence, which may result in a functional change in the protein. This can lead to disease or altered traits.
- Examples: SNPs in the BRCA1 gene are associated with an increased risk of breast cancer, while SNPs in the CYP450 gene can affect drug metabolism.
- Insertions and Deletions (Indels)
- Definition: Indels refer to the insertion or deletion of one or more nucleotides in the DNA sequence. Indels can have significant impacts on the function of genes and regulatory regions.
- Types:
- Short Indels: Typically involve the insertion or deletion of a small number of nucleotides (less than 50 base pairs).
- Long Indels: Involve larger chunks of DNA, which may lead to major disruptions in gene function.
- Effects: Indels can lead to frameshift mutations, changing the reading frame of the gene and potentially resulting in a nonfunctional protein.
- Example: Cystic fibrosis is often caused by a 3-base pair deletion (ΔF508) in the CFTR gene.
- Copy Number Variations (CNVs)
- Definition: CNVs are variations in the number of copies of a particular gene or genomic region. This can involve duplications or deletions of large segments of DNA.
- Types:
- Duplication: A segment of DNA is copied multiple times, increasing the number of copies of certain genes.
- Deletion: A segment of DNA is missing, reducing the number of gene copies.
- Effects: CNVs can affect gene dosage, leading to altered gene expression, which can cause diseases such as autism, schizophrenia, and cancer.
- Example: The CYP2D6 gene can be present in multiple copies, which affects drug metabolism in individuals.
- Variable Number Tandem Repeats (VNTRs)
- Definition: VNTRs are repeating sequences of 2-10 base pairs that are located in non-coding regions of the genome. The number of repeats can vary among individuals, resulting in polymorphism.
- Types:
- Short Tandem Repeats (STRs): Repeats of 1-6 base pairs in length.
- Mini-satellites: Repeats of 6-64 base pairs in length.
- Effects: The number of repeats can influence gene expression or lead to disease. STRs are commonly used in DNA profiling and forensic science.
- Example: The D16S539 marker is a well-known STR used in human identification.
- Restriction Fragment Length Polymorphisms (RFLPs)
- Definition: RFLPs involve variations in the length of restriction enzyme-digested DNA fragments. These variations occur due to changes in restriction enzyme recognition sites or the presence/absence of cutting sites.
- Types:
- Deletion RFLPs: Removal of restriction enzyme recognition sites.
- Insertion RFLPs: The introduction of new recognition sites.
- Effects: RFLPs can be used to identify genetic diseases, study inheritance patterns, and distinguish between different alleles of a gene.
- Example: RFLPs in the APOE gene can be associated with Alzheimer’s disease risk.
- Microsatellites (Simple Sequence Repeats or SSRs)
- Definition: Microsatellites are short sequences of DNA (2-6 base pairs) that are repeated multiple times in tandem. The number of repeats can vary greatly between individuals, making them highly polymorphic.
- Types:
- Dinucleotide repeats: The most common type, where two nucleotides are repeated (e.g., CA).
- Tetranucleotide repeats: Four nucleotides are repeated (e.g., ATGT).
- Effects: Changes in the number of repeats can lead to genetic disorders, especially in regions that regulate gene expression.
- Example: Huntington’s disease is caused by a repeat expansion of CAG trinucleotides in the HTT gene.
- Chromosomal Rearrangements
- Definition: Chromosomal rearrangements involve large-scale changes in chromosome structure, including inversions, translocations, duplications, and deletions.
- Types:
- Inversions: A segment of a chromosome is reversed.
- Translocations: A segment of one chromosome is transferred to another chromosome.
- Deletions/Duplications: As described above, involve large sections of chromosomes.
- Effects: Chromosomal rearrangements can disrupt the normal function of genes and lead to diseases such as chronic myelogenous leukemia (due to a translocation between chromosomes 9 and 22, known as the Philadelphia chromosome).
- Example: Cystic fibrosis and Charcot-Marie-Tooth disease can result from chromosomal rearrangements.
Conclusion
DNA polymorphisms are a source of genetic diversity and play an essential role in genetics, evolution, and human health. Different types of polymorphisms, including SNPs, indels, CNVs, and structural variations, influence a wide array of biological functions and susceptibility to diseases. Understanding these polymorphisms is key to advancing research in genomics, personalized medicine, and human evolutionary studies.