Selection and mutation in the "new" genetics: an emerging hypothesis.

Human Genetics
Bruce GottliebMark Trifiro

Abstract

It has been anticipated that new, much more sensitive, next generation sequencing (NGS) techniques, using massively parallel sequencing, will likely provide radical insights into the genetics of multifactorial diseases. While NGS has been used initially to analyze individual human genomes, and has revealed considerable differences between healthy individuals, we have used NGS to examine genetic variation within individuals, by sequencing tissues "in depth", i.e., oversequencing many thousands of times. Initial studies have revealed intra-tissue genetic heterogeneity, in the form of multiple variants of a single gene that exist as distinct "majority and "minority" variants. This highly specialized form of somatic mosaicism has been found within both cancer and normal tissues. If such genetic variation within individual tissues is widespread, it will need to be considered as a significant factor in the ontogeny of many multifactorial diseases, including cancer. The discovery of majority and minority gene variants and the resulting somatic cell heterogeneity in both normal and diseased tissues suggests that selection, as opposed to mutation, might be the critical event in disease ontogeny. We, therefore, are proposing a hypothesis...Continue Reading

References

Feb 15, 2001·Trends in Genetics : TIG·B GottliebM A Trifiro
Feb 22, 2001·Science·J C VenterX Zhu
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
May 25, 2001·Health Care Analysis : HCA : Journal of Health Philosophy and Policy·B Brülde
Mar 20, 2003·Mutation Research·Robert P Erickson
May 18, 2004·Human Mutation·Bruce GottliebMark Trifiro
Nov 5, 2004·Journal of Evolutionary Biology·M Pineda-Krch, K Lehtilä
Nov 5, 2004·Journal of Evolutionary Biology·J R Pannell, S M Eppley
Nov 5, 2004·Journal of Evolutionary Biology·M J Hutchings, D Booth
Apr 30, 2005·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Liang ChengMichael O Koch
Sep 22, 2006·International Journal of Epidemiology·Paolo Vineis, Marianne Berwick
Nov 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jason H BielasLawrence A Loeb
Jan 11, 2007·European Journal of Human Genetics : EJHG·Joël Zlotogora
Mar 9, 2007·Nature·Daniel A Haber, Jeff Settleman
Apr 19, 2007·Prostate Cancer and Prostatic Diseases·K SircarM Trifiro
Jun 15, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Bruce GottliebMark Trifiro
Aug 10, 2007·Critical Reviews in Biochemistry and Molecular Biology·John W Drake
Aug 22, 2007·Scandinavian Journal of Gastroenterology·Gerhard J MolderingsIvar Von Kügelgen
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Peter J CampbellMichael R Stratton
Nov 15, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Julian E SaleDávid Szüts
Dec 10, 2008·Nature Reviews. Genetics·Gudmundur A ThorissonAnthony J Brookes
Jan 9, 2009·Immunologic Research·Brian R Davis, Fabio Candotti
May 5, 2009·Genome Research·Francisco J Ayala
May 28, 2009·The Journal of Clinical Endocrinology and Metabolism·M Laloi-MichelinUNKNOWN Mitochondrial Diabetes French Study Group
Jun 11, 2009·Human Mutation·Bruce GottliebMorris Schweitzer
Jul 7, 2009·Nature·Avigdor EldarMichael B Elowitz
Aug 12, 2009·Nature Biotechnology·Dmitry PushkarevStephen R Quake
Sep 3, 2009·Journal of Medical Genetics·R Happle
Sep 12, 2009·Annual Review of Pathology·Jesse J SalkLawrence A Loeb
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Randolph M NesseDavid Valle
Dec 18, 2009·Nature·Erin D PleasanceMichael R Stratton
Dec 18, 2009·Nature·Erin D PleasancePeter J Campbell

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Citations

Mar 13, 2013·Regenerative Medicine·Marina V Pryzhkova
Jul 6, 2011·Medical Hypotheses·Roger Pamphlett
Feb 16, 2012·Human Mutation·Bruce GottliebMark Trifiro
Jun 22, 2011·Molecular and Cellular Endocrinology·Diane M Robins
Jun 18, 2014·Current Biology : CB·Steven A Frank
Dec 3, 2014·Genomics, Proteomics & Bioinformatics·Lv JinShao-Qi Rao
Apr 11, 2013·Stem Cells Translational Medicine·Marina V Pryzhkova
Apr 19, 2013·Nature Reviews. Genetics·Leslie G Biesecker, Nancy B Spinner
Mar 20, 2020·Cell Systems·Claire J WatsonRonald Y Kwon
Mar 8, 2021·Thrombosis and Haemostasis·María Del Pilar Valencia-MoralesSilvio Zaina
Nov 28, 2020·Trends in Cancer·Bruce GottliebGerald Batist

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