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A new conceptual framework for investigating complex genetic disease
Some common diseases are known to have an inherited component, however, their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. St...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631989/ https://www.ncbi.nlm.nih.gov/pubmed/26583033 http://dx.doi.org/10.3389/fgene.2015.00327 |
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author | Hussain, Shobbir |
author_facet | Hussain, Shobbir |
author_sort | Hussain, Shobbir |
collection | PubMed |
description | Some common diseases are known to have an inherited component, however, their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. Studies that have attempted to identify the causative genetic factors have been designed on this polygenic framework, but so far the yield has been largely unsatisfactory. Based on accumulating recent observations concerning the roles of somatic mosaicism in disease, in this article a second framework which posits a single gene-two hit model which can be modulated by a mutator/anti-mutator genetic background is suggested. I discuss whether such a model can be considered a viable alternative based on current knowledge, its advantages over the current polygenic framework, and describe practical routes via which the new framework can be investigated. |
format | Online Article Text |
id | pubmed-4631989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-46319892015-11-18 A new conceptual framework for investigating complex genetic disease Hussain, Shobbir Front Genet Genetics Some common diseases are known to have an inherited component, however, their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. Studies that have attempted to identify the causative genetic factors have been designed on this polygenic framework, but so far the yield has been largely unsatisfactory. Based on accumulating recent observations concerning the roles of somatic mosaicism in disease, in this article a second framework which posits a single gene-two hit model which can be modulated by a mutator/anti-mutator genetic background is suggested. I discuss whether such a model can be considered a viable alternative based on current knowledge, its advantages over the current polygenic framework, and describe practical routes via which the new framework can be investigated. Frontiers Media S.A. 2015-11-04 /pmc/articles/PMC4631989/ /pubmed/26583033 http://dx.doi.org/10.3389/fgene.2015.00327 Text en Copyright © 2015 Hussain. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Hussain, Shobbir A new conceptual framework for investigating complex genetic disease |
title | A new conceptual framework for investigating complex genetic disease |
title_full | A new conceptual framework for investigating complex genetic disease |
title_fullStr | A new conceptual framework for investigating complex genetic disease |
title_full_unstemmed | A new conceptual framework for investigating complex genetic disease |
title_short | A new conceptual framework for investigating complex genetic disease |
title_sort | new conceptual framework for investigating complex genetic disease |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631989/ https://www.ncbi.nlm.nih.gov/pubmed/26583033 http://dx.doi.org/10.3389/fgene.2015.00327 |
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