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Updated: Jun 3, 2026
Wild-type Blocking PCR Combined with Direct Sequencing as a Highly Sensitive Method for Detection of Low-Frequency Somatic Mutations
Published on: March 29, 2017
Sequence-specific priming as a rapid screen for known mutations
1NCI-FCRDC, Frederick, MD.
Abstract:
Mutations in a large number of genes have now been identified that ultimately alter the expression or function of the corresponding protein, thereby inducing a particular disease state. These mutations may be found frequently in the disease population, but may also be present to some extent in normal individuals. On the other hand, alterations of the prototypic or wild type allele, again affecting protein expression or function, can result in some level of protection against certain diseases. The latter situation is well-exemplified by an allele of the CCR5 chemokine receptor gene, CCR5△32, which does not encode a functional protein on cell surfaces (see 1 for review). Since CCR5 behaves as a coreceptor with CD4 for macrophage-tropic strains of HIV-1, homozygotes for the CCR5△32 allele are highly, though not completely, protected against HIV-1 infection. Similarly, a single base change in the CCR2 gene, CCR2-64I, is associated with delayed progression to AIDS after HIV-1 infection (2).
Insights
Genetic variations like CCR5△32 and CCR2-64I influence disease susceptibility. Certain gene alleles, such as CCR5△32, offer protection against HIV-1 infection and disease progression.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Genetic mutations can alter protein function, leading to diseases.
- Some genetic variations, however, can confer protection against certain diseases.
- The CCR5 chemokine receptor gene and its CCR5△32 allele are key examples.
Purpose of the Study:
- To explore the role of specific genetic variations in disease protection.
- To highlight the impact of CCR5△32 and CCR2-64I alleles on HIV-1 infection and AIDS progression.
Main Methods:
- Review of existing literature on gene mutations and disease states.
- Analysis of the CCR5△32 allele's effect on HIV-1 susceptibility.
- Examination of the CCR2-64I variant's association with AIDS progression.
Main Results:
- The CCR5△32 allele, resulting in a non-functional CCR5 protein, confers significant protection against HIV-1 infection.
- Individuals homozygous for CCR5△32 are highly resistant to HIV-1.
- The CCR2-64I allele is linked to delayed progression to Acquired Immunodeficiency Syndrome (AIDS) post-HIV-1 infection.
Conclusions:
- Specific genetic alterations in chemokine receptor genes can modulate susceptibility and progression of infectious diseases like HIV-1.
- Understanding these genetic factors is crucial for developing targeted therapeutic and preventative strategies.
