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Methods to Increase the Sensitivity of High Resolution Melting Single Nucleotide Polymorphism Genotyping in Malaria
Published on: November 10, 2015
Profiles of global mutations in the human intercellular adhesion molecule-1 (ICAM-1) shed light on
Jasmita Gill1, Himmat Singh2, Amit Sharma3
1ICMR-National Institute of Malaria Research, Sector-8 Dwarka, New Delhi, India. jasmita.gill@gmail.com.
Abstract:
Plasmodium falciparum is responsible for malaria-related morbidity and mortality. PfEMP1 (P. falciparum erythrocyte membrane protein 1) mediates infected erythrocytes adhesion to various surface vascular receptors, including intercellular adhesion molecule-1 (ICAM-1), associating this interaction with severe malaria in several studies. Genetic variation in host ICAM-1 plays a significant role in determining susceptibility to malaria infection via clinical phenotypes such as the ICAM-1Kilifi variant which has been reported to be associated with susceptibility in populations. Our genomic and structural analysis of single nucleotide polymorphisms (SNPs) in ICAM-1 revealed 9 unique mutations each in its distinct A-type and BC-type PfEMP1 DBLβ-interacting regions. These mutations are noted in only a few field isolates and mainly in the African/African American population. The ICAM-1Kilifi variant lies in a flexible loop proximal to the DBLβ-interacting region. This analysis will assist in establishing functional correlations of reported global mutations via experimental and clinical studies and in the tailored design of population-specific genetic surveillance studies. Understanding host polymorphism as an evolutionary force in diverse populations can help to predict predisposition to disease severity and will contribute towards laying the framework for designing population-specific personalized medicines for severe malaria.
Insights
Genetic variations in intercellular adhesion molecule-1 (ICAM-1) influence malaria severity. Specific ICAM-1 mutations, including the ICAM-1Kilifi variant, are linked to increased susceptibility, particularly in African populations.
Area of Science:
- Genetics
- Immunology
- Parasitology
Background:
- Plasmodium falciparum causes significant malaria morbidity and mortality.
- P. falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite adhesion, linked to severe malaria.
- Host genetic variations, like ICAM-1 polymorphisms, affect malaria susceptibility and clinical outcomes.
Purpose of the Study:
- To analyze genomic and structural variations in ICAM-1 related to PfEMP1 binding.
- To investigate the role of specific ICAM-1 mutations, including the ICAM-1Kilifi variant, in malaria susceptibility.
- To inform the design of population-specific genetic surveillance and personalized medicine strategies.
Main Methods:
- Genomic and structural analysis of single nucleotide polymorphisms (SNPs) in ICAM-1.
- Identification of mutations in PfEMP1 DBLβ-interacting regions.
- Analysis of mutation prevalence in field isolates, particularly from African/African American populations.
Main Results:
- Identified 9 unique mutations in ICAM-1's A-type and BC-type PfEMP1 DBLβ-interacting regions.
- Observed these mutations in a limited number of field isolates, primarily in African/African American individuals.
- Located the ICAM-1Kilifi variant in a flexible loop near the DBLβ-interacting region.
Conclusions:
- Host ICAM-1 polymorphisms are crucial in determining malaria severity.
- Understanding these genetic variations can predict disease predisposition and guide personalized medicine approaches.
- This research supports tailored genetic surveillance for malaria in diverse populations.
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