Change search
ReferencesLink to record
Permanent link

Direct link
Non-heritable genetics of human disease: spotlight on post-zygotic genetic variation acquired during lifetime (Reprinted from vol 50, pg 1-10, 2013)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.ORCID iD: 0000-0002-1701-755X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
2013 (English)In: Postgraduate medical journal, ISSN 0032-5473, E-ISSN 1469-0756, Vol. 89, no 1053, 417-426 p.Article, review/survey (Refereed) Published
Abstract [en]

The heritability of most common, multifactorial diseases is rather modest and known genetic effects account for a small part of it. The remaining portion of disease aetiology has been conventionally ascribed to environmental effects, with an unknown part being stochastic. This review focuses on recent studies highlighting stochastic events of potentially great importance in human disease-the accumulation of post-zygotic structural aberrations with age in phenotypically normal humans. These findings are in agreement with a substantial mutational load predicted to occur during lifetime within the human soma. A major consequence of these results is that the genetic profile of a single tissue collected at one time point should be used with caution as a faithful portrait of other tissues from the same subject or the same tissue throughout life. Thus, the design of studies in human genetics interrogating a single sample per subject or applying lymphoblastoid cell lines may come into question. Sporadic disorders are common in medicine. We wish to stress the non-heritable genetic variation as a potentially important factor behind the development of sporadic diseases. Moreover, associations between post-zygotic mutations, clonal cell expansions and their relation to cancer predisposition are central in this context. Post-zygotic mutations are amenable to robust examination and are likely to explain a sizable part of non-heritable disease causality, which has routinely been thought of as synonymous with environmental factors. In view of the widespread accumulation of genetic aberrations with age and strong predictions of disease risk from such analyses, studies of post-zygotic mutations may be a fruitful approach for delineation of variants that are causative for common human disorders.

Place, publisher, year, edition, pages
2013. Vol. 89, no 1053, 417-426 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-204331DOI: 10.1136/postgradmedj-2012-101322repISI: 000320579700009OAI: diva2:638446
Available from: 2013-07-30 Created: 2013-07-30 Last updated: 2016-09-09Bibliographically approved

Open Access in DiVA

fulltext(499 kB)141 downloads
File information
File name FULLTEXT01.pdfFile size 499 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Forsberg, Lars A.Dumanski, Jan Piotr
By organisation
Medical Genetics
In the same journal
Postgraduate medical journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 141 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 324 hits
ReferencesLink to record
Permanent link

Direct link