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CRISPR-mediated Genome Editing of the Human Fungal Pathogen Candida albicans
Published on: November 14, 2018
Next-generation computational genetic analysis: multiple complement alleles control survival after Candida albicans
Gary Peltz1, Aimee K Zaas, Ming Zheng
1Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA 94305, USA. gpeltz@stanford.edu
Infection and Immunity
|August 31, 2011
Summary
Researchers identified genetic factors influencing survival during Candida albicans infections using a computational mapping program. Variations in complement pathway genes, specifically C1r/s and C5, significantly impact host susceptibility and disease outcomes.
Area of Science:
- Immunology
- Genetics
- Computational Biology
Background:
- Candida albicans is a major fungal pathogen causing life-threatening disseminated infections, particularly in immunocompromised individuals.
- Host genetic factors play a crucial role in determining susceptibility and disease severity during C. albicans infections.
Purpose of the Study:
- To develop and utilize a next-generation computational genetic mapping program to identify host genetic factors influencing survival in a murine model of hematogenous C. albicans infection.
- To elucidate the genetic basis of host susceptibility to C. albicans, with potential implications for other diseases.
Main Methods:
- Development of an advanced computational genetic mapping program.
- Analysis of median survival data from inbred mouse strains infected with C. albicans.
- Validation of computational findings through assessment of C1 binding and survival in chromosome substitution strains.
Main Results:
- Computational analysis identified genetic variation in early classical complement pathway components (C1q, C1r, C1s) as potential determinants of survival.
- Serum C1 binding to C. albicans was significantly influenced by C1rs alleles.
- A combinatorial genetic model involving C5 and C1r/s alleles accurately predicted host survival post-infection.
Conclusions:
- Genetic variations within the classical complement pathway, particularly involving C1r/s and C5, are critical determinants of host survival during C. albicans infection.
- The developed computational tool is effective for identifying host susceptibility factors in infectious disease models.
- Findings may offer insights into genetic predispositions for autoimmune and neurodegenerative diseases.