Epigenetics Revisted

Epigenetics, as it’s name implies is a collection of genome wide alterations that would change the information that is coming out of the genome, without changing the sequence. These changes are heritable from cell division to cell division, and in some cases from parent to offspring. This idea sounds a bit odd the first time around. We get used to thinking about mutation as one of the few ways that gene information can be changed in a heritable way, but it turns out there are more. Biology is smart, or at least it has had allot of time to figure out how to get things done.

As a field toxicology is concerned with the way that the environment effects living organisims and one area of interest has always been genotoxic compounds. Epigenetics adds a new dimension to this as epigenetic changes cause alter gene expression and if you look for examples there are plenty of mechanical changes in the genome of cancer cells that part of the epigenetic machinery. Toxicologist are very interested in what xenobiotics would be involved in altering epigenetic patterns.

Finally there is one more twist that is worth mentioning. I like all biologist of my time grew up thinking of the world using Darwin‘s evolutionary paradigm. There was another contemporary of Darwin that many of us have heard about that is often used as a counterpoint to stress how other scientists of the time thought of change that occurred across species. The cartoon that I can still remember to this day is Jean-Baptiste Lamarck‘s giraffe stretching to eat the leaves higher and higher in the tree. Ridiculous! But wait, epigentics proposes a model by which the environment might actually be able to influence the genome of an organism and produce heritable changes in gene expression. This may not be what Lamarck was thinking of, but it does sound eerily similar.

The toxicology paper is a good review of epigenetic mechanisms and it has a few “gee-wiz” biology examples.. There are however many practical examples of how epigenetics works, and diseases that may have an epigenetic component. I have asked the Tox 1401 students to head on over to OMIM and search using the term “epigenetic”, to find some examples. Look through the comments to see what they have come up with.

55 thoughts on “Epigenetics Revisted

  1. The MLH gene, which is involved in DNA mismatch repair, is also homologous to the E.Coli Mutations in the MLH1 gene can end in ‘hereditary nonpolyposis colorectal cancer’. Cells with these mutations cannot carry out mismatch repair property and bear defects in both alleles of MHL1. The majority of these cells are found to be colorectal tumor cells. BRCA1 proteins are apart of a protein complex including tumor suppressors, DNA damage sensors, and signal transducers. Immunoprecipitation and mass spectrometry are two techniques used to identify proteins such as these. It is this protein that sense abnormalities in DNA structures, such as the mismatch repairs that are unable to fixed, caused by the MHL1 mutations, ultimately resulting in the possibility of colorectal cancer.

    • short and to the point, however informative. I like that it was very direct and to the point because it didn’t leave the reader confused about the information they were provided with.

      • J’nelle, I’m glad you liked my post and felt it was easy to understand. I wasn’t sure if it was to brief, and readers wouldnt be able to understand what I was trying to say.

  2. Lamarckian evolution suggests the direct transfer of physical characteristics from parent to offspring. Jean-Baptiste Lamarck hypothesized that environmental conditions caused phenotypic changes from generation to generation. His ideas were quickly refuted by society at that time and Charles Darwin’s philosophy was accepted. Darwin’s theory of evolution and natural selection was essentially based on ‘survival of the fittest’. It made sense that the animals that lacked the physical traits of survival (beak size, neck length, etc) died and those better suited for the environment survived. Lamarck and other scientist’s genetic research were limited then. With certain biotechnological equipment and other software available today, scientists are interested in validating or ultimately refuting Lamarckian theory.
    Epigenetics refers to the manipulation of DNA and chromatin without changing actual base pairs but rather the way the DNA is imprinted or marked. This involves DNA methylation, demethylation, acetylation, histone activity, and Cp5-dinucleotide activity. Research suggests that the orientation of, addition, or removal of methyl groups has a significant effect on the next generation. Whether chromatin is tightly or loosely wrapped around histones in the nucleus can also affect the expression of certain traits. Offspring cannot inherit certain physical characteristics like height but they can inherit the number of methyl groups, acetyl groups, or histone activity from their parents.
    DNA Methyl Transferase (DNMT1) maintains methylated patterns on the cytosine nucleotide in the genome of mammals (OMIM database). During the formation of gametes and early development, methyl groups are reshaped. Methylation patterns are responsible for gene imprinting and X-inactivation. Gene imprinting is the marking of DNA with specific patterns (methyl, acetyl, or histone, etc) that are passed on to the second generation. Maintenance of methylation leads to normal growth and development of a mammal and any methylation pattern other than the norm is associated with tumorous and cancerous growths. X-activation is when one of the two X chromosomes present in females is inactivated and shows up under a microscope as a Barr body. This is important because the female X chromosome has several more genes compared to the male Y-chromosome. Without inactivation the organism is susceptible to a double dose of X-linked genes which is toxic to a female mammalian organism.

    • I think your explanation of epigenetic was very clear. It’s strange how manipulation of DNA and chromatin without changing actual base pairs but rather the way the DNA is imprinted or marked can cause epigenetic diseases. I totally agree that DNA methylation, demethylation, acetylation, histone activity, and Cp5-dinucleotide activity have a huge role in epigenetic. The addition or removal of methyl groups has a significant effect on the next generation and I also mentioned that on my post. The DNA Methyl Transferase (DNMT1) that you mentioned that maintains methylated patterns on the cytosine nucleotide in the genome of mammals was good, but what disease is caused if the DNMT1 doesn’t maintain the methylated patterns. Overall, you explained everything very well.

    • I think your post was also very clear and very intersting. I agreed with many of your ideas, especially that histone activity may affect epigenetics. This was well organized and very well explained!

  3. The external environment’s effects upon genes can influence disease, and some of these effects can be inherited in humans. These effects are known as epigenetics factors and they are involved in genetic control by factors other than an individual’s DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed. Recently, epigenetic alterations, especially DNA methylation, have been shown to occur in Colorectal Cancer (CRC). DNA methylation, a chemical process that adds a methyl group to DNA, changes have been recognized as one of the most common molecular alterations in human tumors. It is highly specific and always happens in a region in which a cytosine nucleotide is located next to a guanine nucleotide that is linked by a phosphate, also known as CpG site. Researchers found that disease tissue from patients with CRC had less DNA methylation than normal tissue from the same patients.

    In CRC, methylated genes are typically turned off and loss of DNA methylation, hypomethylation, can cause abnormally high gene activation by altering the arrangement of chromatin. However, hypermethylation, too much methylation, can undo the work of protective tumor suppressor genes. There are stretches of DNA near promoter regions that have higher concentrations of CpG sites that are free of methylation in normal cells. These CpG sites become excessively methylated in cancer cells causing genes to turn off that should not be silenced to turn off. This abnormality is the epigenetic change that occurs in tumors and happens early in the development of cancer. Hypermethylation of CpG sites can cause tumors by shutting off tumor suppressor genes. Although epigenetic changes do not alter the sequence of DNA, they can cause mutations. About half of the genes that cause familial or inherited forms of cancer are turned off by methylation. Most of these genes normally suppress tumor formation and help repair DNA.

    The state of DNA methylation appears to play a role in genetic instability in CRC. Many cancers have been shown to have a global hypomethylation of DNA compared with normal tissues. Researchers found a striking correlation between genetic instability and methylation capacity. This suggests that methylation abnormalities may play a role in the chromosome segregation processes in cancer cells. It has been speculated that genetic instability is necessary for a tumor to accumulate the numerous genetic alterations that accompany carcinogenesis, the initiation of cancer formation. The ability to detect these methylated DNA in several body fluids may serve as a possible new screening marker for CRC. There are many CRC patients that are in advance stage of this disease and an early detection can be one of the most important approaches to reduce death rate in these patients. Therefore, an effective screening test can have substantial clinical benefits.


    O’Neill, Morla et al. (2011). Colorectal Cancer; CRC. Gene map locus: 17p11.2, 17p13.1, etc. Johns Hopkins University. MIM ID #114500

    Zitt, M. and Muller, HM (2007). DNA methylation in colorectal cancer. Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria. PMID: 17325426

  4. Epigenetics is the term used when there is a different folding pattern of the genome rather than then an actual nucleotide mutation. The way the genome folds often will “turn on” or “off” a particular gene and if folded differently, genes that should be “off” might just “turn on”. This has proven to me a major source for genetic diseases and it has also been found that the way a genome folds can be passed down from generation to generation creating an inheritance.
    One such disease is Lynch Syndrome I and II (HNPCC) which is a genetically heterogeneous disease. Although there are mutations associated with this disease, a major component of how this disease is expressed falls into the category of epigenetics. Lynch Syndrome is a form of hereditary colorectal cancer (HNPCC) and is divided into two forms depending on where the cancer is found in the body. Several mutated genes are associated with the disease but the origin of all these mutations seem to come from an epigenetic silencing of the MSH2 gene in the TACSTD1. The epigenetic silencing is caused by a deletion of several 3 prime exons of the TACSTD1 gene. This silencing effects the gene MLH1 which is associated with DNA repairs. This particular part of the genome, MSH2, is associated with 60% of the Lynch Syndrome diseases and problems in DNA repair can cause extensive genome problems.
    Lunch Syndrome is a different form of the regular colorectal disease and this is seen through the diagnosis. The tumors that developed were slightly different as well as some symptoms.

    • I liked how you expanded on my post by talking about another form of hereditary colorectal cancer (HNPCC). Your post was good and you explained everything very well. I agree that the way the genome folds often will turn on or off a particular gene, which may lead to epigenetic disease. Lynch Syndrome I and II (HNPCC) that you mentioned, which is a genetically heterogeneous disease, was very interesting and I felt the same way when I talked about Colorectal Cancer (CRC). I totally agree that Lunch Syndrome is a different form of the regular colorectal disease, but I think they are both very unique because they have different pathways that lead to a similar disease. The diagnosis is very important factor in determining similar diseases that are slightly different.

    • I liked your detailed explanations about the disease, it provides the reader with a lot of information about a disease most likely they have not ever known about before. It was also good that you explained the turning “on” and “off” of genes as well.

  5. Epigenetics is a term used to define the study of changes in a phenotype or gene expression caused by different mechanisms other than changes that are in the underlying DNA sequence. Epigenetics causes many different mutations to proteins and structure within our bodies. These different mutations can lead to many different diseases. One such disease is multiple sclerosis, commonly known as MS. Multiple sclerosis is an inflammatory disease where the fatty myelin sheaths around the axons in the brain and spinal cord have become damaged. Susceptibility to MS is associated with a mutation in different human leukocyte antigen (HLA) genes on chromosome 6p21. Although it is considered a mutation on the chromosome the DNA sequence itself in the genome is not changed. This disease is not a hereditary disease. In only 91 cases thus far has MS been linked between generations. Typically this change in phenotype shows up on its own, there aren’t known patterns as to why this disease arouses and whom it effects most. Most patients with MS are treated using interferon-beta therapy, typically from this therapy patients see a significant decline in ‘cellular survivin expression’ within 6-12 months.

    • This blog post is very clear, so it is easy to understand because of the simple terminology used. It is also well organized because it starts off by explaining what epigenetics is and then giving a prime example of it. It was also sourced. Good job!

    • Your response was very straightforward and descriptive. It would have been better if you explained how exactly MS results from brain cells getting damaged. How would the mutations be different from mutations from chemotheraphy? The term DNA being ‘damaged’ is very vague and I think that if you addressed that more, it would be more clear.

    • Your interpretation of epigenetics and an example of it is informative and clear to understand.

  6. Epigenetics involves genetic control by factors other than an individual’s DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed. While epigenetic changes are required for normal development and health, they can also be responsible for some disease states. DNA methylation is a process that adds a methyl group to DNA in a region in which a cytosine nucleotide is located next to a guanine nucleotide that is linked by a phosphate known as CpG site. Insertion of methyl groups can change the appearance and the structure of DNA. The first human disease to be linked to epigenetics was cancer. Patients with colorectal cancer had less DNA methylation than normal tissue from the same patients. Turning off the methylated genes leads to abnormally high gene activation by altering the arrangement of chromatin. However, too much methylation can undo the work of protective tumor suppressor genes. DNA methylation normally occurs at CpG sites; however, there are stretches of DNA near promoter regions that have higher concentrations of CpG sites (known as CpG islands) that are free of methylation in normal cells. These CpG islands become excessively methylated in cancer cells and affect genes that should not be silenced to turn off. Hypermethylation of CpG islands can cause tumors by shutting off tumor-suppressor genes. This epigenetic change happens in the early cancer development.

    • Wow this is intresting; it goes to show you moderation is the key. At first when there was too little methylation, there was too much gene activation leading to cancer. Then when there is too much methylation (in CpG islands) it turns off the protective suppressor genes leading to cancer.
      I just want to know if the CpG islands serves a function in DNA replication or if it just a marker for disease.

  7. Epigenetics is the study of chemical reactions which turn on and off certain parts of our genome and any factors which affects these reactions. There are epigeneticsed interactions between our genome and the environment, which can occur during the development of an embryo. In 2003 scientists Bob Waterman and Randy Jirtle published a paper on the importance of epigenetics in embryonic development and and this article helped make Epigenetics a more widespread field of study. They studied a female yellow agouti mouse. As noted in the study, this specific mouse has two notable characteristics, which are yellow fur color and a tendency to be obese. When a female mouse was fed a diet rich in folic acid and vitamin B12 (rich in methyl), the yellow fur gene of the offspring (agouti gene) was silenced which resulted in offspring with brown fur. It was later learned that when the agouli gene is not expressed, offspring are less likely to have diabetes, cancer and obesity.

    From this experiment Waterman and Jirtle found that adding methyl rich foods to a pregnant human woman’s diet would also have positive effects. For example adding folic acid to a mothers diet can cause the offspring to be less likely to have certain birth defects. However, there is also some speculation that the addition of methyl much foods such as folic acid could have negative epigenetic effects on the offspring. Epigenetics is an important study that must continue to be funded in my opinion because there is potential that it can result in positive developments to combat human diseases.

    • I agree with you that there definetly is a positive side to epigenetics. However, I hope scientists are not harming the mothers or the fetus as they conduct tests such as the methyl food one which you mentioned.

    • I also agree that in the future there can definitely be a great benefit to the up side of the study and gain of knowledge in the field of epigenetics. Overall well written and easy to follow without ‘dumbing it down too much’.

  8. Epigenetics is the study of heritable changes in phenotype or gene expression caused by mechanisms other than a change in DNA sequence. Unlike in a mutation, there is no change in the underlying DNA sequence; it is non-genetic factors that make the organism’s genes to be expressed differently. Basically, epigenetic changes can cause a gene to be overly expressed or may turn off the genes. One way that this may occur is through DNA methylation. Duke University oncologist Randy Jirtle conducted an experiment in which they methylated a mouse containing an agouti gene. This gene gave the mice an inclination for obesity and diabetes. They fed a group of pregnant mice a diet high in B vitamins. B vitamins acted as methyl donors and increased the methylation of the agouti gene. By only altering the diet and not the DNA sequence, the mothers gave birth to healthy pups of normal weight and without diabetes. Thus you can have genetic changes in offspring without altering the DNA sequence.


    • This is a very interesting example. I didin’t know that feeding a rat a diet high in vitamin B could cause an epigenetic change in DNA. It is funny how a vitamin can cause an epigenetic mutation.

    • Very interesting post. I like how you included information about the rat experimen-it was very clear, and interesting, as well as being a very good example for this post’s topic.

    • Your post is very interesting and clearly. The rat experiment is interesting as well.

    • What surprised me about this article was the fact that a diet can cause such a major affect on DNA. Often you would think radiation etc would affect DNA in such a manner but a diet such as this one (high in Vitamin B) is really weird. I really enjoyed reading it and i liked that you included an experiment to explain your reasoning.

      • Wow man, this post nice! It really is interesting to see how huge changes can still occur by phenotype and genotype from a miniature outside influence. Also short and to the point, and your logic on the genetic change was rally easy to follow

      • This is a good well written post that does a clear job at explaining how a little change can make a huge difference. Its like if a strict vegetarian accidentally ate a hamburger they would actually get sick. Its also comparable to depriving a person of a nutrient and watching how they develop as opposed to giving a person excess or normal amounts of the same thing.

  9. The story of epigenetics
    Epigenetics is a term used to describe the change that takes affect on a gene from its environment. This change isn’t necessarily on the order of the structure of the protein but rather, the outer orientation meaning that this change is not a mutation. Because of the new orientation, there will most likely be a new phenotypic outcome. In this scenario, some genes are ‘turned on’ and others are ‘turned off’ when it should happen in reverse for the process to be normal.
    A good example of this is in the phenomenon called zygosity. Zygosity is the characterization of twinning and multiple births in terms of the combination of alleles for particular traits. Although most monozygous (MZ) twins share common genotype, they are mostly not identical. There are many possible reasons as to why this happens but it all boils down to one thing, what were the zygotes exposed to post division.
    Epigenetics can better explain the total phenomenon of differences that takes place within the same phenotype and appear totally different. It’s pretty cool to know that the environment really can shape how one individual is formed.

    (1)MIM ID 276410

    • Hey I am a fraternal twin and I agree that both my brother and I do not look alike. This can be argued by some because when my brother’s friends see me, they think I am him and vice versa. Now that we are a lot older, environmental factors played a large part in our appearance. By that I mean exposure to sun, diet and exercise which makes us for differentiable. So I agree that the environment does have a large role in how the individual is formed.

    • Its also important to remember epigenetics does not only affect phenotypic characteristics. Rather it is the pattern of imprining that is changed or maintained. Examples of imprinting include: methylaiton, demethylation, acylation, and histone activity.

    • I like your post, and I also have read about the article that is related to your post. Yes, “although most monozygous (MZ) twins share common genotype, they are mostly not identical.” And the environment also has impacts on the differences between twins.

  10. Epigenetic is the study of heritable changes in gene expression that happens without a change in the DNA sequence. Research has shown that epigenetic mechanisms provide an “extra” layer of transcriptional control that regulates how genes are expressed. These mechanisms are critical components in the normal development and growth of cells. Epigenetic abnormalities have been found to be a causative factor in cancer, genetic disorders and pediatric syndromes as well as a contributing factor in autoimmune diseases and aging. Epigenetic modifications include addition of molecules, like methyl groups, to the DNA backbone. Adding these groups changes the appearance and structure of DNA, altering how a gene can interact with important interpreting transcribing molecules in the cell’s nucleus. Commonly defined as the study of heritable changes in gene function that occurs without a change in the DNA sequence, epigenetic is reshaping the way scientists look at traditional genetics. Genes carry the blueprints to make proteins in the cell. Because they change how genes can interact with the cell’s transcribing machinery, epigenetic modifications, generally turn genes on or off, allowing or preventing the gene from being used to make a protein. There are different kinds of epigenetic marks, chemical additions to the genetic sequence. The addition of methyl groups to the DNA backbone is used on some genes to distinguish the gene copy inherited from the father and that inherited from the mother. In this situation, known as “imprinting,” the marks both distinguish the gene copies and tell the cell which copy to use to make proteins.

  11. Epigenetics is the study of heritable changes in an organism’s appearance or gene expression caused by a change that does not affect the DNA sequence. These changes may remain through cell divisions for the remainder of the cell’s life and may also last for multiple generations. The non-genetic factors alter the organism’s genes causing changes in the organism and possibly causing disease. An example of an epigenetic mechanism is abnormal epigenetic regulation in hematopoietic cells. In the Bottardi et al. paper, two transgenic mice (mice that had been injected with genetic material that did not come from the mice) was used as models to “demonstrate that heritable alteration of chromatin organization at the human β-globin locus in multipotent hematopoietic progenitors contributes to the abnormal expression of the β-globin gene in mature erythroid cells” This was cause by histonecovalent modifications that are inherited during erythropoiesis. Genes regulated is through the remodeling of chromatin. The modifications include can include acetylation, methylation, ubiquitylation, phosphorylation or sumoylation. Chromatin is the complex of DNA and the histone proteins. Histone proteins are little spheres that DNA wraps around. If the way that DNA is wrapped around the histones changes, gene expression can change as well.

    In the paper they suggest that the human β-gene –promoter are epigenetically marked by histone H3 acetylation/k4 dimethylation in human. The histone methylation serves as a signal for a gene to get expressed or suppressed. In the paper it discussed how “position effect variegation (PEV) pattern of human β-gene expression appears to be linked to the disruption of chromatin potentiation. PEV is characterized by the activity of a gene that is restricted to a subset of cell. Since the histone modification is important for the potentiation of the human β-globin gene in the bone marrow this defect can cause sickle cell anemia and thalassemia because of the reduced amount of beta chains.


    • Your explanation on epigenetics is clear and easy to understand. I agree with you on if the way that DNA is wrapped around the histones changes, gene expression can alter as well.

  12. Epigenetics is the study of gene activity that involves changing the information that is coming out of the genome, without changing the sequence. These alterations can be passed down from parent to offspring. These epigenetic marks govern the patterns of gene expression and turn the genes on and off. They are also the reason why environmental factors such as diet and stress can make an imprint on genes that can be passed on genetically. Therefore lifestyle changes such as smoking and over-eating can manipulate the epigenetic marks on top of DNA which can cause the genes for obesity to express themselves. This can influence diseases to one’s off springs before they are even conceived. Many diseases may have an epigenetic component. For instance, Beckwith-Wiedemann syndrome (BWS) is caused by mutation or deletion of imprinted genes in chromosome 11p15.5 region. BWS is a pediatric overgrowth disorder which can cause tumor development. Huntington disease could also be caused by genetic imprinting. Hunting disease (HD) is an autosomal dominant progressive neurodegeneration disorder. By imprinting, the gene is modified in regards to methylation of DNA.

    MIM ID #130650
    MIM ID #143100

  13. Epigenetic is the study of heritable changes in gene function that occur without a change in the sequence of the DNA. There are a lot of diseases like that one of them is Silver-Russell syndrome. It is a disorder present at birth that involves poor growth, low birth weight, short height, and differences in the size of the two sides of the body. The disorder often results from the abnormal regulation of certain genes that control growth. An estimated some of patients with this syndrome have a defect called the maternal uniparental disomy (UPD) for chromosome 7. In other of patients, there is an abnormality on chromosome 11 that affects growth genes. Also in most patients a cause cannot be identified. Researchers found out that almost all cases of Russell-Silver syndrome result from changes in a process called methylation. Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. Russell-Silver syndrome has been associated with changes in methylation involving the H19 and IGF2 genes, which are located near one another on chromosome 11. These genes are thought to be involved in directing normal growth. A loss of methylation disrupts the regulation of these genes, which leads to slow growth and the other characteristic features of this disorder.

  14. Epigenetics is the study of how gene expression is expressed differently through the environmental changes without any directly changes of the genetic genome. In the case of monozygotic (MZ) twins, the two individual may have the common genotype from their parents. The twin pairs are not identical due to the difference of epigentics, the way the genes are expressed in their own bodies, which resulted in the differences in genotypes. In 2005, through the examination of the global and locus-specific difference in DNA methylation and histone acetylation of the MZ twin Fraga et al. had concluded that the younger MZ twins are epigenetically identical to each other. However, later on as the MZ twins grow up, the MZ twins express their gene differently due to the contribution of their own DNA methylation and histone acetylation. In one of their experiment, the patterns of X inactivation between the two MZ twins were being examined. Through amplification of inter-methylated sites (AIMS), DNA methylation between 3 year-old MZ twins and 50 year-old was examined, few differential bands that corresponded the sibling-specific changes of DNA methylation were indicated. The chromosomal region of the MZ twins and the promoter CpG island region were also examined using AIMS and Southern blot, Bisulfite genomic sequencing respectively. All the experiments all resulted in the same conclusion that MZ twins gene would have similar gene expression at their early age, but as their grow older, the gene expression would change differently.
    MIM ID 276410

    • I like the amount of support you gave for epigenetics but i felt that you could have focussed on explaining what methylation is and how it relates to epigenetics. You gave a lot of facts and I feel that if some of the facts were broken down a bit, the response would have been very thought out.

  15. An organisms development and maintenance is ensemble by sets of chemical reactions that turns its genes on and off at calculated times and spot. Epigenetic is said to be the study of such reactions and factors that manipulate them to create changes. These factors include environmental changes such as stress, diet, and so on.
    Let’s take for example the H19 gene located on chromosome 11. The gene is expressed on one parental allele through imprinting. It is transcribe from the mothers inherited allele. It is said to have a role in some cancers, like breast cancer and Beckwith-Wiedemann syndrome.
    In this case the mother is said to be stamped since she is carrying that gene, during the egg and sperm formation. The stamping process is known as methylation, where chemical reaction attaches methyl groups to certain segment of DNA. For instance, in people with Beckwith-Wiedemann syndrome, the ICR1 region is in charge of the genomic imprinting of H19 gene and also the IGF2 gene. Once this region is hypermethylated, having too many methyl groups attached, it interrupts the regulation of these genes. Hypermethylation of the ICR1 region causes a failure of H19 gene activity, which stops growth of a tumor, and increases the activity of IGF2 gene, which promotes growth, therefore causing an over growth of tumor in people with the syndrome.

    Reference: http://ghr.nlm.nih.gov/gene/H19

  16. Epigenetics is a study of heritable changes in the phenotypes of proteins. These changes however have nothing to do with the DNA itself. The DNA itself has nothing wrong with it. Studies found out that these epigenetic changes occur in many illnesses, especially in cancers. Due to the mitosis of cells, the epigenetic change in one cell can multiply rapidly and pervade throughout not only one part of the body but also throughout the whole body. One example of epigenetic change is Huntington’s Disease. It is a neurodegenerative genetic disorder that notable physical symptoms such as jerky, random, and uncontrollable movements called chorea. Cognitive abilities get progressively worse .this disease usually occurs in the middle age. Studies have shown that environmental factors can contribute to Huntington’s disease. This shows that even though for example a group of people that has Huntington’s disease. Each of them may show a little bit of different symptoms because they grew up in different places. During imprinting, an epigenetic change in the methylation of the DNA could cause the Huntington’s Disease’s symptoms to manifest itself.

  17. The H19 gene encodes a sequence that is not translated and that is expressed exclusively from the mother’s allele. The human H19 gene is 2.7 kb long and includes 4 small introns. It is a developmentally regulated gene with alleged tumor suppressor capabilities. Researchers have hypothesized that the loss of H19 expression may be involved in Wilms tumorigenesis. Wilms tumorigenesis arises from arrested differentiation of renal progenitor cells. An in-situ hybridization analysis of the H19 expression was performed during normal rabbit development and in human atherosclerotic plaques. The results found were that the H19 expression in developing skeletal and smooth muscles correlated with specific differentiation events in these tissues. The expression of H19 in the skeletal muscle correlated with nonproliferative, actin-positive muscle cells. They were also able to identified H19-positive cells in adult atherosclerotic lesions, which suggest that these cells may repeat early developmental events. These results, along with the identification of the insulin family of growth factors as potent regulatory molecules for H19 expression, provided additional clues toward understanding the physiologic regulation and function of H19.
    Source: http://www.ncbi.nlm.nih.gov/omim/103280

  18. Epigenetics is the alteration in gene expression caused by factors outside the genome. Examples of epigenetics includes environmental factors, diet and stress. In the molecular level, histones play a major role in epigenetics. Histones offer DNA a wrapping mechanism to save space in the nucleus. It is now clear that histones play a different role. Depending on if the histones are acetylated or methylated, some genes are either turned on or off.
    In a recent study of lung cancer, epigenetic alterations like promoter methylation have been detected. It was seen that methylation of CALCA, CDH1, DAPK1, and EVX2 genes was more common when exposed to squamous cell carcinomas. An abundant number of promoter methylation was observed in non-small cell lung cancer in which 48- 84% of the promoters were methylated in the 4 genes. This causes a different phenotype for the lung cells and promotes tumor formation. Furthermore, there was an increased PIK3CA gene mutation and is associated with a smoking history in humans. Although epigenetics and mutations are two different things, it is still viable to say that epigenetics may be the cause of some mutations in the body.

    Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC).2011 Apr 20. Ji M, Guan H, Gao C, Shi B, Hou P.
    PMID: 21507233

  19. Genes carry the design to life. The DNA contained in a gene is transcribed into RNA, which is then translated into the sequence of a certain protein. Although every cell in a particular body has the exact same genetic information, what makes every cell, tissue and organ different is which gene is turned and therefore expressed. For example, neuronal and epithelial cells have different functions because they have specific genes that are expressed while others are turned off. The term epigenetics implies all of the modifications done to genes besides the mutations in the sequence. Some of these modifications consist of the addition of different molecules, such as methyl groups. The addition of these groups can change the way a gene can interact with other parts of the nucleus of a cell by changing the form and structure of the DNA. These modifications can also turn a gene on or off, either permitting or averting the gene from being used to make proteins. Mutations, in contrast, affect not only the sequence of the DNA, but also change the function of a protein. One such gene that is involved in the mythelation process is MECP2. Mutations in this gene have been linked to a neurodegenerative disease known as Rett Syndrome.
    The MECP2 gene is located on the X chromosome at the xq28 region and contains 4 exons. It is vital to the production of a protein, MECP2, which is paramount for the healthy development of the brain. MECP2 a chromatin-associated protein that binds methylated CpGs. CpG islands are pieces of genomic DNA that consist of a cytosine and guanine separated by a phosphate group and when methylated can turn a certain gene off. What makes this protein unique is that it is dependent upon methyl CpGs for its dispersal among the chromosomes. Other inquiries imply that this protein also plays a major part in creating synapses between nerve cells for cell-to-cell communication and suppresses the translation of DNA sequences, preventing the formation of certain proteins that are not required.
    Mutations in the MECP2 gene have been traced to the development of a condition known as Rhett syndrome. Some of the mutations that were observed in the cause of Rett syndrome were novel mutations, or new mutations and frameshift deletions, which is a mutation that causes codons to be read incorrectly during translation. Rhett syndrome is a disorder that is usually sporadic, but there are few cases where the condition is passed down through a family. This neurological and developmental disorder occurs predominantly in females. Since females have one active X chromosome (the other becoming a Barr body), a portion of the cells in the nervous system of a girl that has Rett syndrome will use the faulty gene. The other portion of the cells will use the healthy gene to produce regular amounts of protein. For the females that do suffer from Rhett syndrome, they experience symptoms, such as loss of speech, loss of important hand movements, balance and coordination, breathing problems, anxiety and developmental disabilities. The seriousness of this disease is dependent on which copy of the gene a majority of the cells use. If the effective X chromosome that is utilizing the defective gene is turned off, the symptoms will be mild. However, if the active X chromosome that is manipulating the normal MECP2 gene is turned off, inception of the disorder can begin early and be more severe. Nevertheless, it is an entirely different case for males. This is because males have only one X chromosome, meaning that they have no support to save them from the dangerous effects of this condition. Most boys that suffer from Rhett syndrome feel their effects when they are first-born and unfortunately die soon after.


    Works Cited
    Downer, Joanna. Backgrounder: Epigenetics and Imprinted Genes. 15 November 2002.
    Eunice Kennedy Shriver NICD. Rett Syndrome. 02 August 2010.
    Genetics Home Reference. MECP2. April 2006.
    Online Mendelian Inheritance in Man. METHYL-CpG-BINDING PROTEIN 2; MECP2
    MIM ID *300005.
    NINDS. Rett Syndrome Fact Sheet. 16 February 2011.
    Oxford Journals. MECP2 mutations account for most cases of typical forms of Rett syndrome.
    23 March 2000. http://hmg.oxfordjournals.org/content/9/9/1377.full

  20. Epigenetics involves one’s DNA sequence where there are genes that can be ‘on’ or ‘off’. This will lead to which proteins will be expressed or not. An example of an epigenetic disease is Huntington Disease, which is under the category of neurodegeneration. This disease is characterized by uncoordination at many times and physical instability. It was found that there was a ‘short arm’ of chromosome 4 which may be ‘off’ for individuals that have Huntington disease. This is due to a over-repeated sequence of CAG on chromosome 4; therefore, it may be not be able to go through with apoptosis. If the number of repeated sequences is over 37, the individual may be diagnosed with Huntington disease. There are many theories on why this happens, such as genes that may protect the myelin sheath or mitochondrial dysfunction.
    source: 143100

  21. I really liked how you went about organizing your information in the blog. By describing what epigenetics was and then going on to describe your disease really made things clear. Also I liked how you about explaining methylation and how it was associated with your disease and epigenetics. You made something that can be confusing a little more understandable. It turns out that the disease I used for my post is a derivative of the disease you described.

  22. The apc gene plays a major role in the tumor suppression by antagonizing with the wingless-type (WNT). Molecular Location on chromosome 5: base pairs 112,043,217 to 112,181,935. The apc encodes a multidomain protein and when this pathway is inapprotiately activated it can contribute to cancer progression. It also takes on a role in cell migration, adhesion. There were several cases where the apc gene was found to suppress a tumor. i.e. Hoshino et al., Mastumine et al., Roose et al. basically the apc gene regulates the cell division cycle by keeping the cells dividing or growing too fast. If this gene is mutated it can create diseases in the person’s body. Most people will develop colorectal cancer and there can be some disorder in the human body called Turcot syndrome.

  23. Epigenetics is the study of heritable changes in gene function that occur without a change in sequence of the DNA. It’s when there is another influence on the expression of genes; a system in addition to the direct translation of the genetic information. Genetic imprinting and x-inactivation are epigenetic systems found in humans. In X-inactivation, both men and women have equal expression of the genes carried on the X chromosome; even though the women have two X chromosomes and the male has one X and one Y chromosome. The inactivation begins at the X chromosome inactivation center, consisting of genetic elements that are necessary for inactivation.

  24. Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness.It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social or occupational dysfunction. Due to similars symptoms characterized in both, researchers were trying to find out if schizophrenia and bipolar disorder were two distinct disorders or were more connected. Two years ago researchers in Sweden suggest a common genetic cause for the two conditions. Epigenetic misregulation is consistent with various nonmendelian features of schizophrenia and bipolar disorder. Microarray testin was used to identify DNA methylation changes in the frontal cortex and germline associated with schizophrenia and bipolar disorder. In the frontal cortex they found evidence for psychosis-associated DNA methylation differences in numerous loci. DNA methylation changes in a significant proportion of these loci corresponded to reported changes of steady-state mRNA levels associated with psychosis. Methylome network analysis uncovered decreased epigenetic modularity in both the brain and the germline of affected individuals, suggesting that systemic epigenetic dysfunction may be associated with major psychosis. The experiment also included evidence for a strong connection between DNA methylation in the promoter region of the MEK1 gene and lifetime of antipsychotic use in schizophrenia patients. Scientists also observed that the frontal cortex DNA methylation in the BDNF gene was correlated with genotype at a nearby nonsynonymous SNP that had been associated with major psychosis. The data was consistant enough to suggest that DNA DNA methylation changes are important to the etiology of schizophrenia and bipolar disorder.

    MIM ID #181500

  25. Epigenetics is the study of genetic changes in phenotype or the appearance of a gene that is expressed. This change in the appearance of the genes are caused by something other than a actual change in the DNA sequence. The changes undergone by the DNA may stay in the cell for the rest of the cell’s life. It can also last for multiple generations through the spread of cell division.
    The APC gene encodes a protein with multiple domains that plays a major role in the suppression of tumors by antagonizing the WNT signaling pathway. When activation of this pathway is not working properly through the loss of APC function, cancer progression speeds up. “APC also has a role in cell migration, adhesion, chromosome segregation, spindle assembly, apoptosis, and neuronal differentiation.”

  26. Epigenetics is the study of stable alterations in gene expression potential that can arise during the development stage or cell proliferation. When is comes to regulating genes, chromatin played an important role. Its considered the complex of DNA and the remodeling of its structure can cause changes in gene expression. Some ways remodeling can be done is by adding a methyl group to the DNA or post translational modification of Amino Acids that make up the proteins associated with it.

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