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[Entry posted at 18th March 2010 06:00 PM GMT]
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Researchers have identified a possible mechanism by which DNA regions that don't encode proteins can still determine phenotypic traits such as a person's height or susceptibility to a particular disease, researchers report online in Science today.
Moreover, they found that this chromatin variation is associated with distinct single nucleotide polymorphisms, suggesting that the variation may serve as a platform to enable these SNPs -- often found in non-coding regions of DNA -- to influence phenotype.
"This is quite novel," saidEmmanouil Dermitzakis,a geneticist at the University of Geneva Medical School, who was not involved in the study. "Epigenetics has been used as a term that is orthogonal to genetics. This study clearly shows it's not."
Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) to particular diseases or characteristics, but how SNPs relate to phenotype has been unclear. Because SNPs often occur in non-coding regions of the genome, researchers have generally thought that what links these regions to phenotype are processes that control how genes are regulated, but such a relationship has never been demonstrated. "What this paper really does is show this to be the case," said Vishwanath Iyer of the University of Texas at Austin, one of study's three lead authors.
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Read more here/Leia mais aqui: The Scientist
Published Online March 18, 2010
Science DOI: 10.1126/science.1184655
Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans
Read more here/Leia mais aqui: The Scientist
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Science DOI: 10.1126/science.1184655
Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans
Ryan McDaniell,1 Bum-Kyu Lee,1 Lingyun Song,2,3 Zheng Liu,1,* Alan P. Boyle,2 Michael R. Erdos,4Laura J. Scott,4,5 Mario A. Morken,4 Katerina S. Kucera,2 Anna Battenhouse,1 Damian Keefe,6Francis S. Collins,4 Huntington F. Willard,2 Jason D. Lieb,7 Terrence S. Furey,2 Gregory E. Crawford,2,3,Vishwanath R. Iyer,1, Ewan Birney6,
The extent to which variation in chromatin structure and transcription factor binding may influence gene expression and thus underlie or contribute to variation in phenotype is unknown. To address this question, we have cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific, and a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, suggesting that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differs on the basis of genetic variation and may underlie phenotypic variation in humans.
1 Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA.
2 Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
3 Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC 27708, USA.
4 Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
5 Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
6 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1RQ, UK.
7 Department of Biology, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
* Present address: MedImmune, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
The extent to which variation in chromatin structure and transcription factor binding may influence gene expression and thus underlie or contribute to variation in phenotype is unknown. To address this question, we have cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific, and a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, suggesting that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differs on the basis of genetic variation and may underlie phenotypic variation in humans.
1 Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA.
2 Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
3 Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC 27708, USA.
4 Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
5 Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
6 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1RQ, UK.
7 Department of Biology, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
* Present address: MedImmune, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
To whom correspondence should be addressed. E-mail: greg.crawford@duke.edu (G.E.C.); vishy@mail.utexas.edu(V.R.I.); birney@ebi.ac.uk (E.B.)
Received for publication 13 November 2009. Accepted for publication 25 February 2010.
Received for publication 13 November 2009. Accepted for publication 25 February 2010.
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