SlideShare uma empresa Scribd logo
1 de 7
Baixar para ler offline
Epigenetics and Methylation
Shubhda Roy
Dennis Lloyd Jr.
December 4, 2006
Epigenetics
In Bioinformatics, we often consider the effect of the genetic code: how do we find
genes in the genome; what proteins do the genes code for; what are the shape and
function of those proteins. However, an important and emerging research area is arising
within genetic and bioinformatics study: epigenetics. Epigenetics is the study of gene
expression and suppression, and how these phenomena affect genetic and other
biological processes. Various epigenetic properties may be passed from one generation
to another and may also develop throughout the lifetime of an individual. The
inheritance of epigenetic properties is often referred to as “cell memory”.1
Epigenetics
also describes the important specialization of cells from a common set of stem cells.
Epigenetic changes can last generations and be affected by environmental factors such
as diet, exposure to toxins and the nurturing care of parents. One study found that the
offspring of rats exposed to a fungicide while pregnant had lower sperm counts. While
this did not surprise the researchers, they were amazed to find that after several
generations, the descendants still had lower sperm counts. The epigenetic effects of
fungicide exposure had carried for several generations. But all these changes are
temporary and reversible since they arise from regulatory mechanism and do not cause
a genetic mutation.2
Epigenetic changes bring about a phenotypic change in the cell
functionality but the genotype does not change since the nucleotides remains the same.
Since the time when scientists laid the initial foundations for heredity through DNA, the
concept of epigenetics has been hotly contested. However, new research has given
significant evidence for many types of epigenetic systems existing within the cell. Each
epigenetic system attempts to describe the biological processes at work on gene
expression and how these factors are inherited through cell division and reproduction.
Epigentics determines the cell functionality of the stem cells and the state of the cell is
called epigenome.
Types of Epigenetic Systems1
Gene silencing and promotion may result from variations in RNA transcripts and their
protein products. For example, an active gene may code for a protein product that
regulates that same gene or other genes. During cell division, RNA transcripts and
proteins are transferred to the daughter cells and they continue to regulate the genes of
the copied chromosomes. Currently, research is being conducted to determine how
RNA may be passed from parent to child through the egg and sperm cells.
1
Another type of protein epigenetic system works by passing on what are known as
prions. Prions are proteins that have an abnormal structural conformation such that they
cause the abnormal conformation of other proteins. These dysfunctional distorted
proteins are often present in cells due to infection and might be passed during cell
division.
Structural elements of the cell are also inherited through cell division. For example, the
cellular plasma membrane and various organelles are replicated during cell division.
These structures may have properties that yield certain phenotypes that are inherited by
the daughter cells.
DNA takes on its compact form within the nucleus of a cell because it is wrapped
around structural proteins known as histones. The DNA bonds to the histones such that
gene expression only occurs at points where the DNA is capable of unwinding from the
histone, allowing room for transcription. Enzymes within the cell can alter the chemical
bonding properties of the histones, making it more or less difficult for expression of
genes neighboring the histone. This is known as a chromatin-marking system. Much
research is being devoted to understanding how the marking of histones affects gene
expression. It is believed that chromatin-marking may occur primarily during cell division
because the histones are more exposed to the enzymes within the cell at this time.
One project, located at National Human Genome Research Institute, is collecting
sequences of histone proteins. Histone protein sequences are cross-linked to the NCBI
Entrez database and are aligned through multiple sequence alignment using the
CLUSTAL-W and MUSCLE algorithms. Users of the database may enter sequence
fragments and narrow their searches by specifying species and histone type.
One final form of epigenetic inheritance is known as methylation. This epigenetic
system will be the focus of the remainder of this paper.
Methylation
One of the most researched epigenetic systems is the study of methylation. Methylation
is the process of attaching a methyl group (CH3) to the 5-carbon of the pyrimidine ring
of cytosine. This may eventually silence a gene. There are specific places within a DNA
sequence where methylation is likely to occur. These are places where cytosine is
present next to guanine, abbreviated as CpG and referred to as the CG dinucleotide.
This is different from the bond formed by cytosine and guanine in the DNA double-helix.
Methylation at a CpG site is abbreviated as 5mCpG. The ratio of the number of 5mCpG
sites to CpG sites in a sequence is the percent of methylation.
2
3
CpG sites may be methylated or de-methylated, causing genes to be suppressed or
expressed. A change in DNA methylation often effects the growths of certain cancers.
For example, de-methylation of certain genes may cause cells to reproduce
uncontrollably, while methylation of tumor suppressing genes may cause increase in
growth of tumors leading to cancer.1,4
The link between methylation and parental nurturing was studied by researchers
observing methylation of certain genes affecting the hippocampus in the brains of rats.
The study conducted by Michael Meaney and Ian Weaver showed that parental
nurturing by mother rats through licking and grooming their young had significant
impacts on the amount of methylation of a gene that contributes to the growth of the
hippocampus. They were able to measure significant differences in the amount of gene
expression between highly methylated samples taken from nurtured rats and low
methylated samples taken from rats that did not receive adequate nurturing.
Specifically, they were studying methylation on a promoter region for the glucocorticoid
receptor gene which is known to have an effect on reactions to stress. Behavioral
differences are observable in the rats; those that where were nurtured by their mothers
were less skittish due to the secretion of serotonin the happy happy harmone.5
Contrarily rats not nurtured were more nervous if left in a new environment due to
secretion of stress hormones.
DNA Methylation Database
In recent years there has been a growing interest in DNA methylation leading to a
growing amount of data on this topic. To make it easily available for research, a public
database has been established known as DNA Methylation Database or MethDB6
. At
present, this is the only dedicated database which is consistently growing and holds
methylation patterns and profiles. Currently MethDB contains data for 46 species, 160
tissues and 72 phenotypes, resulting from 6667 experiments as of September 4, 2002.7
The submission of data has increased in the last few years providing the genetic
community with a resource to standardize DNA methylation data. This database has
gained popularity and acceptance over the years.
MethDB publishes the method used for each experiment, preventing repetition of an
existing experiment. Earlier methyl patterns were only represented numerically. Now
3
pictorial representation in array like formats is available, making it easier to compare
experiments. In the picture below, each row represents an individual test subject from
which samples are taken. Each block represents a sample taken from that individual.
They are color coded to represent healthy and unhealthy tissue. The shading of the
circles within the block represents the percent methylation of the CpG sites within the
sample.
There is a direct correlation between tissue and the phenotypic stage in the case of
DNA methylation as epigenetic markers. Therefore the tool contains short descriptions
for tissues and disease types that are referenced in the database. MethDB allows for
textual and pictorial annotation as shown below:
It also contains an online submission tool to make new additions to the database easier.
Methylation Tools
For new studies, it is important to determine what level of methylation has occurred at
given genomic sites and if there is any correlation between level of methylation and
4
disease states. To aid in this analysis, a package of methylation tools is available for
download or use over the Internet (results are automatically e-mailed to the user)8
.
As input, the tools take a series of aligned sequences which may have been aligned
using a tool such as CLUSTAL-W. The sequences used will include one reference
sequence and other sequences that have been obtained using a technique called
bisulfite genomic sequencing. Bisulfite genomic sequencing is a process by which
converts un-methylated cytosine to uracil, leaving methylated cytosine intact. This way,
the sequencing tracks where methylation has occurred. Having appropriately aligned
sequences is critical for getting meaningful results from these tools.
Included in the output are two graphs useful for analyzing methylation at the genomic
site of interest. The first graph, shown below, depicts the alignment of the sequences.
Unmethylated CpG sites are shown in blue whereas methylated sites are shown in red.
If sequences are known to represent phenotypes, this graph can help determine if
methylation is a factor and indicate which methylated sites are important.
Another graph of interest
shows the density distribution of
methylation within the aligned
sequences. The height of this graph
represents the percent methylation
while the color represents the
number of sequences with
that percentage.
Conclusion
Epigenetic information helps in the interpretation of DNA expression and suppression in
each cell. Alongside genetic mutation, it is extremely important in deciphering disease
pathways. In the past, epigenetic theory was not taken seriously due to lack of tools to
make the theory a reality. Today with the tight integration of bioinformatics tools,
genomic databases and millions of experiments, research has increased tremendously.
With modern tools available it is easy to organize, analyze, compare and interpret
massive amounts of data patterns. Epigenetic research is helpful in pharmaceutical and
agricultural industry and for society in general. The concept that environment and
nutrition can alter the development of a fetus and that sometimes these changes last
through generation is breaking new ground on understanding biological processes,
disease and potential treatments. We are beginning to realize the responsibility we have
for taking care of ourselves throughout life as this may affect future generations. In the
future, it may be possible that one could take tailored ‘methyl diets’ to stay healthy for
life. Perhaps this can be a reality once the mystery behind epigenetics and a plethora of
diseases, such cancer, is discovered.
References
5
1
Epigenetics at Wikipedia. Accessed online Nov 26, 2006 at:
http://en.wikipedia.org/wiki/Epigenetics
2
Watters, Ethan. DNA is Not Destiny. Discover. Nov, 2006. pg 33-37; 75.
3
Department of Biological Sciences – Graduate School of Science and School of Science. Osaka
University, Japan. http://www.sci.osaka-u.ac.jp/introduction/eng/biology.html
4
The University of Texas. M. D. Anderson Cancer Center. DNA Methylation in Cancer.
http://www.mdanderson.org/departments/methylation/
5
Weaver, Ian, et al. Epigenetic programming by maternal behavior. Accessed online Nov 26, 2006
at http://www.mindfully.org/Health/2004/Maternal-Epigenetic-Programming1aug04.htm
6
Grunau, Christoph. MethDB DNA Methylation Database. Accessed online Nov 26, 2006 at
http://www.methdb.de/
7
Amoreira, Celine; Hindermann, Winfried, and Grunau, Christoph. An Improved Version of the
DNA Methylation Database (MethDB). Nucleic Acid Research. Accessed online Nov 26,2006 at
http://nar.oxfordjournals.org/cgi/content/full/31/1/75
8
Grunau, Christoph; Schattevoy, Ruben; Mache, Niels; Rosenthal, André. MethTools: a toolbox to
visualize and analyze DNA methylation data. Accessed online Nov 27, 2006 at
http://methdb.igh.cnrs.fr/methtools/
1
Epigenetics at Wikipedia. Accessed online Nov 26, 2006 at:
http://en.wikipedia.org/wiki/Epigenetics
2
Watters, Ethan. DNA is Not Destiny. Discover. Nov, 2006. pg 33-37; 75.
3
Department of Biological Sciences – Graduate School of Science and School of Science. Osaka
University, Japan. http://www.sci.osaka-u.ac.jp/introduction/eng/biology.html
4
The University of Texas. M. D. Anderson Cancer Center. DNA Methylation in Cancer.
http://www.mdanderson.org/departments/methylation/
5
Weaver, Ian, et al. Epigenetic programming by maternal behavior. Accessed online Nov 26, 2006
at http://www.mindfully.org/Health/2004/Maternal-Epigenetic-Programming1aug04.htm
6
Grunau, Christoph. MethDB DNA Methylation Database. Accessed online Nov 26, 2006 at
http://www.methdb.de/
7
Amoreira, Celine; Hindermann, Winfried, and Grunau, Christoph. An Improved Version of the
DNA Methylation Database (MethDB). Nucleic Acid Research. Accessed online Nov 26,2006 at
http://nar.oxfordjournals.org/cgi/content/full/31/1/75
8
Grunau, Christoph; Schattevoy, Ruben; Mache, Niels; Rosenthal, André. MethTools: a toolbox to
visualize and analyze DNA methylation data. Accessed online Nov 27, 2006 at
http://methdb.igh.cnrs.fr/methtools/

Mais conteúdo relacionado

Mais procurados

Comparative genomics and proteomics
Comparative genomics and proteomicsComparative genomics and proteomics
Comparative genomics and proteomicsNikhil Aggarwal
 
Personalized Medicine and the Omics Revolution by Professor Mike Snyder
Personalized Medicine and the Omics Revolution by Professor Mike SnyderPersonalized Medicine and the Omics Revolution by Professor Mike Snyder
Personalized Medicine and the Omics Revolution by Professor Mike SnyderThe Hive
 
Comparative genomics @ sid 2003 format
Comparative genomics @ sid 2003 formatComparative genomics @ sid 2003 format
Comparative genomics @ sid 2003 formatsidjena70
 
Drug Discovery: Proteomics, Genomics
Drug Discovery: Proteomics, GenomicsDrug Discovery: Proteomics, Genomics
Drug Discovery: Proteomics, GenomicsPhilip Bourne
 
Molecular basis of evolution and softwares used in phylogenetic tree contruction
Molecular basis of evolution and softwares used in phylogenetic tree contructionMolecular basis of evolution and softwares used in phylogenetic tree contruction
Molecular basis of evolution and softwares used in phylogenetic tree contructionUdayBhanushali111
 
A Systems Biology Approach to Natural Products Research
A Systems Biology Approach to Natural Products ResearchA Systems Biology Approach to Natural Products Research
A Systems Biology Approach to Natural Products ResearchHuda Nazeer
 
proteomics and system biology
proteomics and system biologyproteomics and system biology
proteomics and system biologyNawfal Aldujaily
 
BITS - Introduction to comparative genomics
BITS - Introduction to comparative genomicsBITS - Introduction to comparative genomics
BITS - Introduction to comparative genomicsBITS
 
What is comparative genomics
What is comparative genomicsWhat is comparative genomics
What is comparative genomicsUsman Arshad
 
Comparative genomics
Comparative genomicsComparative genomics
Comparative genomicsprateek kumar
 
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...Varij Nayan
 
Cytoscape: Gene coexppression and PPI networks
Cytoscape: Gene coexppression and PPI networksCytoscape: Gene coexppression and PPI networks
Cytoscape: Gene coexppression and PPI networksBITS
 
Genomics and proteomics by shreeman
Genomics and proteomics by shreemanGenomics and proteomics by shreeman
Genomics and proteomics by shreemanshreeman cs
 
Introduction to epigenetics and study design
Introduction to epigenetics and study designIntroduction to epigenetics and study design
Introduction to epigenetics and study designamlbinder
 

Mais procurados (20)

Comparative genomics and proteomics
Comparative genomics and proteomicsComparative genomics and proteomics
Comparative genomics and proteomics
 
Personalized Medicine and the Omics Revolution by Professor Mike Snyder
Personalized Medicine and the Omics Revolution by Professor Mike SnyderPersonalized Medicine and the Omics Revolution by Professor Mike Snyder
Personalized Medicine and the Omics Revolution by Professor Mike Snyder
 
Comparative genomics @ sid 2003 format
Comparative genomics @ sid 2003 formatComparative genomics @ sid 2003 format
Comparative genomics @ sid 2003 format
 
Comparitive genomics
Comparitive genomicsComparitive genomics
Comparitive genomics
 
Drug Discovery: Proteomics, Genomics
Drug Discovery: Proteomics, GenomicsDrug Discovery: Proteomics, Genomics
Drug Discovery: Proteomics, Genomics
 
Bio
BioBio
Bio
 
Molecular basis of evolution and softwares used in phylogenetic tree contruction
Molecular basis of evolution and softwares used in phylogenetic tree contructionMolecular basis of evolution and softwares used in phylogenetic tree contruction
Molecular basis of evolution and softwares used in phylogenetic tree contruction
 
A Systems Biology Approach to Natural Products Research
A Systems Biology Approach to Natural Products ResearchA Systems Biology Approach to Natural Products Research
A Systems Biology Approach to Natural Products Research
 
proteomics and system biology
proteomics and system biologyproteomics and system biology
proteomics and system biology
 
Bio Lab Paper
Bio Lab PaperBio Lab Paper
Bio Lab Paper
 
BITS - Introduction to comparative genomics
BITS - Introduction to comparative genomicsBITS - Introduction to comparative genomics
BITS - Introduction to comparative genomics
 
What is comparative genomics
What is comparative genomicsWhat is comparative genomics
What is comparative genomics
 
Comparative genomics
Comparative genomicsComparative genomics
Comparative genomics
 
Genomics
GenomicsGenomics
Genomics
 
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...
 
Genomics
GenomicsGenomics
Genomics
 
Cytoscape: Gene coexppression and PPI networks
Cytoscape: Gene coexppression and PPI networksCytoscape: Gene coexppression and PPI networks
Cytoscape: Gene coexppression and PPI networks
 
Genomics and proteomics by shreeman
Genomics and proteomics by shreemanGenomics and proteomics by shreeman
Genomics and proteomics by shreeman
 
Epigenetics & Gene Control
Epigenetics & Gene ControlEpigenetics & Gene Control
Epigenetics & Gene Control
 
Introduction to epigenetics and study design
Introduction to epigenetics and study designIntroduction to epigenetics and study design
Introduction to epigenetics and study design
 

Semelhante a Epigeneticsand methylation

Recurrent Incidence Of Babesiosis Among Adults Essay
Recurrent Incidence Of Babesiosis Among Adults EssayRecurrent Incidence Of Babesiosis Among Adults Essay
Recurrent Incidence Of Babesiosis Among Adults EssayNicole Savoie
 
Gene Therapy And Its Effects
Gene Therapy And Its EffectsGene Therapy And Its Effects
Gene Therapy And Its EffectsRobyn Champagne
 
BIOINFORMATICS Applications And Challenges
BIOINFORMATICS Applications And ChallengesBIOINFORMATICS Applications And Challenges
BIOINFORMATICS Applications And ChallengesAmos Watentena
 
Bioinformatics, application by kk sahu sir
Bioinformatics, application by kk sahu sirBioinformatics, application by kk sahu sir
Bioinformatics, application by kk sahu sirKAUSHAL SAHU
 
4.4 genetic engineering & biotechnology
4.4 genetic engineering & biotechnology4.4 genetic engineering & biotechnology
4.4 genetic engineering & biotechnologycartlidge
 
Chapter 20 ppt
Chapter 20 pptChapter 20 ppt
Chapter 20 pptrehman2009
 
Dna profiling presentation x2
Dna profiling presentation x2Dna profiling presentation x2
Dna profiling presentation x2Eli Rosenthal
 
Dna profiling presentation x2
Dna profiling presentation x2Dna profiling presentation x2
Dna profiling presentation x2teamchaotex
 
Day 6 September 15th Chapters 3 and 5
Day 6 September 15th Chapters 3 and 5Day 6 September 15th Chapters 3 and 5
Day 6 September 15th Chapters 3 and 5Amy Hollingsworth
 
How Genes Change Overtime And The Structure And Function...
How Genes Change Overtime And The Structure And Function...How Genes Change Overtime And The Structure And Function...
How Genes Change Overtime And The Structure And Function...Sunshine Blackburn
 
Bioinformatics manual
Bioinformatics manualBioinformatics manual
Bioinformatics manualkvnsai
 
Fat Body Sequencing Analysis
Fat Body Sequencing AnalysisFat Body Sequencing Analysis
Fat Body Sequencing AnalysisTammy Davis
 
Epigenetic
EpigeneticEpigenetic
EpigeneticSmawi GH
 

Semelhante a Epigeneticsand methylation (20)

Recurrent Incidence Of Babesiosis Among Adults Essay
Recurrent Incidence Of Babesiosis Among Adults EssayRecurrent Incidence Of Babesiosis Among Adults Essay
Recurrent Incidence Of Babesiosis Among Adults Essay
 
Epigenetics
EpigeneticsEpigenetics
Epigenetics
 
Epigenetic Research Paper
Epigenetic Research PaperEpigenetic Research Paper
Epigenetic Research Paper
 
Gene Therapy And Its Effects
Gene Therapy And Its EffectsGene Therapy And Its Effects
Gene Therapy And Its Effects
 
Epigenetics
EpigeneticsEpigenetics
Epigenetics
 
BIOINFORMATICS Applications And Challenges
BIOINFORMATICS Applications And ChallengesBIOINFORMATICS Applications And Challenges
BIOINFORMATICS Applications And Challenges
 
Bioinformatics
BioinformaticsBioinformatics
Bioinformatics
 
Bioinformatics, application by kk sahu sir
Bioinformatics, application by kk sahu sirBioinformatics, application by kk sahu sir
Bioinformatics, application by kk sahu sir
 
4.4 genetic engineering & biotechnology
4.4 genetic engineering & biotechnology4.4 genetic engineering & biotechnology
4.4 genetic engineering & biotechnology
 
Chapter 20 ppt
Chapter 20 pptChapter 20 ppt
Chapter 20 ppt
 
Dna profiling presentation x2
Dna profiling presentation x2Dna profiling presentation x2
Dna profiling presentation x2
 
Dna profiling presentation x2
Dna profiling presentation x2Dna profiling presentation x2
Dna profiling presentation x2
 
Day 6 September 15th Chapters 3 and 5
Day 6 September 15th Chapters 3 and 5Day 6 September 15th Chapters 3 and 5
Day 6 September 15th Chapters 3 and 5
 
Gene Translicing
Gene TranslicingGene Translicing
Gene Translicing
 
How Genes Change Overtime And The Structure And Function...
How Genes Change Overtime And The Structure And Function...How Genes Change Overtime And The Structure And Function...
How Genes Change Overtime And The Structure And Function...
 
Pdb Enzyme Lab
Pdb Enzyme LabPdb Enzyme Lab
Pdb Enzyme Lab
 
Epigenetics
EpigeneticsEpigenetics
Epigenetics
 
Bioinformatics manual
Bioinformatics manualBioinformatics manual
Bioinformatics manual
 
Fat Body Sequencing Analysis
Fat Body Sequencing AnalysisFat Body Sequencing Analysis
Fat Body Sequencing Analysis
 
Epigenetic
EpigeneticEpigenetic
Epigenetic
 

Mais de Shubhda Roy

Vemurafenib in multiple nonmelanoma cancers with braf v600 shubhda roy
Vemurafenib in multiple nonmelanoma cancers with braf v600 shubhda royVemurafenib in multiple nonmelanoma cancers with braf v600 shubhda roy
Vemurafenib in multiple nonmelanoma cancers with braf v600 shubhda royShubhda Roy
 
Phi netics business_plan powerpoint - final
Phi netics business_plan powerpoint - final Phi netics business_plan powerpoint - final
Phi netics business_plan powerpoint - final Shubhda Roy
 
Parkinson's business plan team three
Parkinson's business plan   team threeParkinson's business plan   team three
Parkinson's business plan team threeShubhda Roy
 
Induction of functional hepatocyte like cells from mouse fibroblasts
Induction of functional hepatocyte like cells from mouse fibroblastsInduction of functional hepatocyte like cells from mouse fibroblasts
Induction of functional hepatocyte like cells from mouse fibroblastsShubhda Roy
 
Cell cell communication between malaria-infected red blood cells via
Cell cell communication between malaria-infected red blood cells viaCell cell communication between malaria-infected red blood cells via
Cell cell communication between malaria-infected red blood cells viaShubhda Roy
 
Amarani therapeutics.inc 12 03_2015.
Amarani therapeutics.inc 12 03_2015.Amarani therapeutics.inc 12 03_2015.
Amarani therapeutics.inc 12 03_2015.Shubhda Roy
 
Preventing Preterm Birth via Stem Cells
Preventing Preterm Birth via Stem CellsPreventing Preterm Birth via Stem Cells
Preventing Preterm Birth via Stem CellsShubhda Roy
 

Mais de Shubhda Roy (12)

Epigenetics[1]
Epigenetics[1]Epigenetics[1]
Epigenetics[1]
 
Vemurafenib in multiple nonmelanoma cancers with braf v600 shubhda roy
Vemurafenib in multiple nonmelanoma cancers with braf v600 shubhda royVemurafenib in multiple nonmelanoma cancers with braf v600 shubhda roy
Vemurafenib in multiple nonmelanoma cancers with braf v600 shubhda roy
 
Preta
PretaPreta
Preta
 
Phi netics business_plan powerpoint - final
Phi netics business_plan powerpoint - final Phi netics business_plan powerpoint - final
Phi netics business_plan powerpoint - final
 
Pharma abcd inc
Pharma abcd incPharma abcd inc
Pharma abcd inc
 
Parkinson's business plan team three
Parkinson's business plan   team threeParkinson's business plan   team three
Parkinson's business plan team three
 
Induction of functional hepatocyte like cells from mouse fibroblasts
Induction of functional hepatocyte like cells from mouse fibroblastsInduction of functional hepatocyte like cells from mouse fibroblasts
Induction of functional hepatocyte like cells from mouse fibroblasts
 
Herceptin
HerceptinHerceptin
Herceptin
 
Com^3.ppt
Com^3.pptCom^3.ppt
Com^3.ppt
 
Cell cell communication between malaria-infected red blood cells via
Cell cell communication between malaria-infected red blood cells viaCell cell communication between malaria-infected red blood cells via
Cell cell communication between malaria-infected red blood cells via
 
Amarani therapeutics.inc 12 03_2015.
Amarani therapeutics.inc 12 03_2015.Amarani therapeutics.inc 12 03_2015.
Amarani therapeutics.inc 12 03_2015.
 
Preventing Preterm Birth via Stem Cells
Preventing Preterm Birth via Stem CellsPreventing Preterm Birth via Stem Cells
Preventing Preterm Birth via Stem Cells
 

Último

Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationMedicoseAcademics
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...Shubhanshu Gaurav
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisSujoy Dasgupta
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.pptRamDBawankar1
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Peter Embi
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 

Último (20)

Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosis
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 

Epigeneticsand methylation

  • 1. Epigenetics and Methylation Shubhda Roy Dennis Lloyd Jr. December 4, 2006 Epigenetics In Bioinformatics, we often consider the effect of the genetic code: how do we find genes in the genome; what proteins do the genes code for; what are the shape and function of those proteins. However, an important and emerging research area is arising within genetic and bioinformatics study: epigenetics. Epigenetics is the study of gene expression and suppression, and how these phenomena affect genetic and other biological processes. Various epigenetic properties may be passed from one generation to another and may also develop throughout the lifetime of an individual. The inheritance of epigenetic properties is often referred to as “cell memory”.1 Epigenetics also describes the important specialization of cells from a common set of stem cells. Epigenetic changes can last generations and be affected by environmental factors such as diet, exposure to toxins and the nurturing care of parents. One study found that the offspring of rats exposed to a fungicide while pregnant had lower sperm counts. While this did not surprise the researchers, they were amazed to find that after several generations, the descendants still had lower sperm counts. The epigenetic effects of fungicide exposure had carried for several generations. But all these changes are temporary and reversible since they arise from regulatory mechanism and do not cause a genetic mutation.2 Epigenetic changes bring about a phenotypic change in the cell functionality but the genotype does not change since the nucleotides remains the same. Since the time when scientists laid the initial foundations for heredity through DNA, the concept of epigenetics has been hotly contested. However, new research has given significant evidence for many types of epigenetic systems existing within the cell. Each epigenetic system attempts to describe the biological processes at work on gene expression and how these factors are inherited through cell division and reproduction. Epigentics determines the cell functionality of the stem cells and the state of the cell is called epigenome. Types of Epigenetic Systems1 Gene silencing and promotion may result from variations in RNA transcripts and their protein products. For example, an active gene may code for a protein product that regulates that same gene or other genes. During cell division, RNA transcripts and proteins are transferred to the daughter cells and they continue to regulate the genes of the copied chromosomes. Currently, research is being conducted to determine how RNA may be passed from parent to child through the egg and sperm cells. 1
  • 2. Another type of protein epigenetic system works by passing on what are known as prions. Prions are proteins that have an abnormal structural conformation such that they cause the abnormal conformation of other proteins. These dysfunctional distorted proteins are often present in cells due to infection and might be passed during cell division. Structural elements of the cell are also inherited through cell division. For example, the cellular plasma membrane and various organelles are replicated during cell division. These structures may have properties that yield certain phenotypes that are inherited by the daughter cells. DNA takes on its compact form within the nucleus of a cell because it is wrapped around structural proteins known as histones. The DNA bonds to the histones such that gene expression only occurs at points where the DNA is capable of unwinding from the histone, allowing room for transcription. Enzymes within the cell can alter the chemical bonding properties of the histones, making it more or less difficult for expression of genes neighboring the histone. This is known as a chromatin-marking system. Much research is being devoted to understanding how the marking of histones affects gene expression. It is believed that chromatin-marking may occur primarily during cell division because the histones are more exposed to the enzymes within the cell at this time. One project, located at National Human Genome Research Institute, is collecting sequences of histone proteins. Histone protein sequences are cross-linked to the NCBI Entrez database and are aligned through multiple sequence alignment using the CLUSTAL-W and MUSCLE algorithms. Users of the database may enter sequence fragments and narrow their searches by specifying species and histone type. One final form of epigenetic inheritance is known as methylation. This epigenetic system will be the focus of the remainder of this paper. Methylation One of the most researched epigenetic systems is the study of methylation. Methylation is the process of attaching a methyl group (CH3) to the 5-carbon of the pyrimidine ring of cytosine. This may eventually silence a gene. There are specific places within a DNA sequence where methylation is likely to occur. These are places where cytosine is present next to guanine, abbreviated as CpG and referred to as the CG dinucleotide. This is different from the bond formed by cytosine and guanine in the DNA double-helix. Methylation at a CpG site is abbreviated as 5mCpG. The ratio of the number of 5mCpG sites to CpG sites in a sequence is the percent of methylation. 2
  • 3. 3 CpG sites may be methylated or de-methylated, causing genes to be suppressed or expressed. A change in DNA methylation often effects the growths of certain cancers. For example, de-methylation of certain genes may cause cells to reproduce uncontrollably, while methylation of tumor suppressing genes may cause increase in growth of tumors leading to cancer.1,4 The link between methylation and parental nurturing was studied by researchers observing methylation of certain genes affecting the hippocampus in the brains of rats. The study conducted by Michael Meaney and Ian Weaver showed that parental nurturing by mother rats through licking and grooming their young had significant impacts on the amount of methylation of a gene that contributes to the growth of the hippocampus. They were able to measure significant differences in the amount of gene expression between highly methylated samples taken from nurtured rats and low methylated samples taken from rats that did not receive adequate nurturing. Specifically, they were studying methylation on a promoter region for the glucocorticoid receptor gene which is known to have an effect on reactions to stress. Behavioral differences are observable in the rats; those that where were nurtured by their mothers were less skittish due to the secretion of serotonin the happy happy harmone.5 Contrarily rats not nurtured were more nervous if left in a new environment due to secretion of stress hormones. DNA Methylation Database In recent years there has been a growing interest in DNA methylation leading to a growing amount of data on this topic. To make it easily available for research, a public database has been established known as DNA Methylation Database or MethDB6 . At present, this is the only dedicated database which is consistently growing and holds methylation patterns and profiles. Currently MethDB contains data for 46 species, 160 tissues and 72 phenotypes, resulting from 6667 experiments as of September 4, 2002.7 The submission of data has increased in the last few years providing the genetic community with a resource to standardize DNA methylation data. This database has gained popularity and acceptance over the years. MethDB publishes the method used for each experiment, preventing repetition of an existing experiment. Earlier methyl patterns were only represented numerically. Now 3
  • 4. pictorial representation in array like formats is available, making it easier to compare experiments. In the picture below, each row represents an individual test subject from which samples are taken. Each block represents a sample taken from that individual. They are color coded to represent healthy and unhealthy tissue. The shading of the circles within the block represents the percent methylation of the CpG sites within the sample. There is a direct correlation between tissue and the phenotypic stage in the case of DNA methylation as epigenetic markers. Therefore the tool contains short descriptions for tissues and disease types that are referenced in the database. MethDB allows for textual and pictorial annotation as shown below: It also contains an online submission tool to make new additions to the database easier. Methylation Tools For new studies, it is important to determine what level of methylation has occurred at given genomic sites and if there is any correlation between level of methylation and 4
  • 5. disease states. To aid in this analysis, a package of methylation tools is available for download or use over the Internet (results are automatically e-mailed to the user)8 . As input, the tools take a series of aligned sequences which may have been aligned using a tool such as CLUSTAL-W. The sequences used will include one reference sequence and other sequences that have been obtained using a technique called bisulfite genomic sequencing. Bisulfite genomic sequencing is a process by which converts un-methylated cytosine to uracil, leaving methylated cytosine intact. This way, the sequencing tracks where methylation has occurred. Having appropriately aligned sequences is critical for getting meaningful results from these tools. Included in the output are two graphs useful for analyzing methylation at the genomic site of interest. The first graph, shown below, depicts the alignment of the sequences. Unmethylated CpG sites are shown in blue whereas methylated sites are shown in red. If sequences are known to represent phenotypes, this graph can help determine if methylation is a factor and indicate which methylated sites are important. Another graph of interest shows the density distribution of methylation within the aligned sequences. The height of this graph represents the percent methylation while the color represents the number of sequences with that percentage. Conclusion Epigenetic information helps in the interpretation of DNA expression and suppression in each cell. Alongside genetic mutation, it is extremely important in deciphering disease pathways. In the past, epigenetic theory was not taken seriously due to lack of tools to make the theory a reality. Today with the tight integration of bioinformatics tools, genomic databases and millions of experiments, research has increased tremendously. With modern tools available it is easy to organize, analyze, compare and interpret massive amounts of data patterns. Epigenetic research is helpful in pharmaceutical and agricultural industry and for society in general. The concept that environment and nutrition can alter the development of a fetus and that sometimes these changes last through generation is breaking new ground on understanding biological processes, disease and potential treatments. We are beginning to realize the responsibility we have for taking care of ourselves throughout life as this may affect future generations. In the future, it may be possible that one could take tailored ‘methyl diets’ to stay healthy for life. Perhaps this can be a reality once the mystery behind epigenetics and a plethora of diseases, such cancer, is discovered. References 5
  • 6. 1 Epigenetics at Wikipedia. Accessed online Nov 26, 2006 at: http://en.wikipedia.org/wiki/Epigenetics 2 Watters, Ethan. DNA is Not Destiny. Discover. Nov, 2006. pg 33-37; 75. 3 Department of Biological Sciences – Graduate School of Science and School of Science. Osaka University, Japan. http://www.sci.osaka-u.ac.jp/introduction/eng/biology.html 4 The University of Texas. M. D. Anderson Cancer Center. DNA Methylation in Cancer. http://www.mdanderson.org/departments/methylation/ 5 Weaver, Ian, et al. Epigenetic programming by maternal behavior. Accessed online Nov 26, 2006 at http://www.mindfully.org/Health/2004/Maternal-Epigenetic-Programming1aug04.htm 6 Grunau, Christoph. MethDB DNA Methylation Database. Accessed online Nov 26, 2006 at http://www.methdb.de/ 7 Amoreira, Celine; Hindermann, Winfried, and Grunau, Christoph. An Improved Version of the DNA Methylation Database (MethDB). Nucleic Acid Research. Accessed online Nov 26,2006 at http://nar.oxfordjournals.org/cgi/content/full/31/1/75 8 Grunau, Christoph; Schattevoy, Ruben; Mache, Niels; Rosenthal, André. MethTools: a toolbox to visualize and analyze DNA methylation data. Accessed online Nov 27, 2006 at http://methdb.igh.cnrs.fr/methtools/
  • 7. 1 Epigenetics at Wikipedia. Accessed online Nov 26, 2006 at: http://en.wikipedia.org/wiki/Epigenetics 2 Watters, Ethan. DNA is Not Destiny. Discover. Nov, 2006. pg 33-37; 75. 3 Department of Biological Sciences – Graduate School of Science and School of Science. Osaka University, Japan. http://www.sci.osaka-u.ac.jp/introduction/eng/biology.html 4 The University of Texas. M. D. Anderson Cancer Center. DNA Methylation in Cancer. http://www.mdanderson.org/departments/methylation/ 5 Weaver, Ian, et al. Epigenetic programming by maternal behavior. Accessed online Nov 26, 2006 at http://www.mindfully.org/Health/2004/Maternal-Epigenetic-Programming1aug04.htm 6 Grunau, Christoph. MethDB DNA Methylation Database. Accessed online Nov 26, 2006 at http://www.methdb.de/ 7 Amoreira, Celine; Hindermann, Winfried, and Grunau, Christoph. An Improved Version of the DNA Methylation Database (MethDB). Nucleic Acid Research. Accessed online Nov 26,2006 at http://nar.oxfordjournals.org/cgi/content/full/31/1/75 8 Grunau, Christoph; Schattevoy, Ruben; Mache, Niels; Rosenthal, André. MethTools: a toolbox to visualize and analyze DNA methylation data. Accessed online Nov 27, 2006 at http://methdb.igh.cnrs.fr/methtools/