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In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
Gene defects in the soma: some get it and some don't!
Bernice Lo1, Michael J Lenardo
1Laboratory of Immunology, NIAID, NIH, Bethesda, Maryland 20892-1892, USA.
The Journal of Clinical Investigation
|December 25, 2010
Summary
Somatic genetic variations, arising during life, are implicated in autoimmune diseases. Researchers found these changes in Fas death receptor genes in patients with autoimmune lymphoproliferative syndrome (ALPS), explaining severe symptoms.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- Somatic DNA variations, acquired throughout life, are increasingly studied beyond cancer.
- Autoimmune lymphoproliferative syndrome (ALPS) is a congenital disorder characterized by defective apoptosis and autoimmunity, typically linked to germline FAS mutations.
Purpose of the Study:
- To investigate the role of somatic genetic alterations in the pathogenesis of severe autoimmune lymphoproliferative syndrome (ALPS).
- To explore the mechanism of somatic loss of heterozygosity in the context of autoimmune diseases.
Main Methods:
- Analysis of somatic DNA variations in patients with ALPS.
- Focus on the Fas death receptor gene (FAS) and its germline normal allele.
- Identification of an unusual T cell population in ALPS patients.
Main Results:
- Somatic alterations were documented in the germline normal FAS allele within a specific subset of T cells in ALPS patients.
- These somatic changes contribute to severe disease manifestations in individuals with ALPS.
- The study highlights the applicability of the oncological concept of somatic loss of heterozygosity to autoimmune diseases.
Conclusions:
- Somatic genetic variations, particularly in the FAS gene, play a significant role in the development and severity of ALPS.
- The findings extend the understanding of genetic mechanisms underlying autoimmune diseases.
- This research bridges concepts from oncology and autoimmunity, revealing shared pathogenetic pathways.
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