Somatic Variants: New Kids on the Block in Human Immunogenetics
Somatic variants are not inherited but acquired during an individual’s lifetime, and individuals are increasingly considered as complex mosaics of genetically distinct cells. Whereas this concept is long-recognized in cancer, this review focuses on the growing role of somatic variants in immune cell...
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| Published in: | Trends in genetics Vol. 35; no. 12; pp. 935 - 947 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Elsevier Ltd
01-12-2019
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Somatic variants are not inherited but acquired during an individual’s lifetime, and individuals are increasingly considered as complex mosaics of genetically distinct cells. Whereas this concept is long-recognized in cancer, this review focuses on the growing role of somatic variants in immune cells in nonmalignant immune-related disorders, such as primary immunodeficiency and autoimmune diseases. Older case reports described somatic variants early in development, leading to large numbers of affected cells and severe phenotypes. Thanks to technological evolution, it is now feasible to detect somatic variants occurring later in life and affecting fewer cells. Hence, only recently is the scale at which somatic variants contribute to monogenic diseases being uncovered and is their contribution to complex diseases being explored systematically.
Somatic variants arise frequently, at least one order of magnitude more often than germline variants. They can occur early in development or later in life, and lead to mosaicism in a wide range or a specific subset of cell lineages.Somatic mosaicism is an under-recognized cause of monogenic immune disorders. Moreover, gonosomal mosaicism in mostly unaffected or sometimes mildly affected parents can lead to vertical transmission of a presumed de novo germline variant.Somatic variants may act as stochastic factors increasing risk of complex diseases together with inherited germline variants and environmental risk factors.Somatic variants tagging cells involved in immune pathogenesis may act as biomarkers guiding treatment.Improving technologies will facilitate detection of somatic variants affecting smaller cell subsets. Integration of germline and somatic genomes may provide novel insights into disease pathogenesis. |
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| Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
| ISSN: | 0168-9525 |
| DOI: | 10.1016/j.tig.2019.09.005 |