Honorable Mention Excerpts



Jason Lam
Stuyvesant High School, NY
Teacher: Maria Nedwidek

In the end, methylation is critically important to the causation of a disease because it can break up a very delicate chain of events that must occur in a specific way. In the case of Fragile X, methylation stops the creation of mRNA for the FMR1 gene which subsequently leads to no FMRP protein being translated. This has disastrous outcomes (mental retardation and physical deformities) for the organism because of the very important function the protein has in regulating translation in the neurons. Thus, it shows how critical and specific gene regulation (in this case, methylation) must occur to maintain the health of the organism.

Monica Woolley
Punahou School, HI
Teacher: Marguerite Ashford

It is gene regulation, for example, which designates cells of the human body to become skin cells, liver cells, and pancreatic cells; it is also thanks to gene regulation that pancreatic cells excrete insulin instead of hemoglobin, and only on an as-needed basis. This places a heavy responsibility on gene regulation to maintain health and properly create a living organism. It is this reliance and dependency which turns small errors in gene regulation into enormous health issues with widespread consequences. A single error in gene regulation can lead to a debilitating disease with lifelong reverberations.

Lindsay Leigler
Tesoro High School, CA
Teacher: Megan Gray

Environmental toxins such as heavy metals disrupt DNA methylation in chromatin, and these changes are inherited by subsequent generations. (Feinberg). In addition, the reported epigenetic changes associated with exposure to smoking, pollution, and poor diets are similar to the epigenetic alterations found in patients with cardiovascular disease. (Ordovas and Smith). This research has led scientists to believe that our environment is indeed responsible for some of the epigenetic changes to chromatin which lead to disease.

Emily Kragel
Junius H. Rose High School, NC
Teacher: Jedediah Smith

The process of methylation is important in gene regulation. Depending on cell type, methylation blocks transcription by blocking the promoter regions where transcription factors are supposed to bind. Studies have shown that methylation of promoters is correlated with low amounts or no transcription. 3 Methylation occurs at the cytosine bases of DNA. The enzymatic addition of a methyl group to these bases converts them to 5- methylcytosine. There are two types of enzymes involved in methylation, de novo DNA methyltransferase (DNMT) and maintenance DNMTs. De novo DNMTs begin methylation by being the first to place methyl groups on a sequence of DNA. Maintenance DNMTs are involved in the continuation of methylation process during the replication of DNA. The modified cytosine base is found (with few exceptions) throughout genomes at CpG sites, places in the DNA sequence where cytosine nucleotides are found next to a guanine nucleotide. This means that there are normally two methylated cytosine bases diagonal to each other on both sides of the stand of DNA. 4 This is an important characteristic of methylation because when DNA replicates, the inactivation of this gene will be passed down when the cell replicates since it is found on both strands.

Brian Lue
The John Cooper School, TX
Teacher: Holly Barlaam

Perhaps most surprising of all, epigenetics seem to also “keep records” which are then passed down through generations. A study in 2002 of a parish in northern Sweden revealed shocking evidence: that there was a connection between the parents’ and grandparents’ diet and their children’s risk of diabetes and cardiovascular disease (Kaati, Bygrin, & Edvinsson, 2002). …

An explanation for this phenomenon could lie in epigenetics and its transgenerational abilities, called epigenetic inheritance (Kaati, Bygrin, & Edvinsson, 2002). Epigenetic inheritance occurs when epigenetic structure of an organism is passed down to its offspring. It is considered to be non-Mendelian, as it cannot be explained by “changes to the primary DNA sequence” (Daxinger & Whitelaw, 2012, p.2), and has been observed in a wide array of organisms ranging from bacteria and fungi to mice and plants (Jablonka & Raz, 2009).

Kristen Datta
St. Paul Academy and Summit School, MN
Teacher: Tina Barsky

X chromosome inactivation is also a vital function of DNA methylation. X chromosome inactivation is a female specific process in which one of the female’s two X chromosomes is methylated (this is different than genomic imprinting because it involves the entire chromosome) creating what is called a “Barr Body.” Which X chromosome is inactivated randomly occurs in early embryonic development, and varies from cell to cell (Phillips et. al., 2008).

Vivienne Chen
Montgomery Blair High School, MD
Teacher: Angelique Bosse

Cancer has long been a topic of intense interest and research. However, many details behind the causes of cancer were unknown until the connection between epigenetic mechanisms and cancer was discovered. Cancer can be caused by genetic mutations that transform normal cells into uncontrollably dividing tumor cells. What has intrigued many researchers, however, is how cancer can develop in the absence of gene mutation. Epigenetic mechanisms may provide an explanation for this puzzle. They do not affect DNA sequences, but rather influence the expression of oncogenes, which can cause cancer, of proto-oncogenes, which are able to become oncogenes, and of tumor suppressor genes, which normally inhibit tumor growth.

Tejas Sundaresan
North Carolina School of Science and Mathematics, NC
Teacher: Myra Halpin

Both miRNA and siRNA are derived from precursor RNA molecules cleaved to 20-25 nucleotide lengths by an RNase called Dicer. One of the strands of the interfering RNA binds Argonaute to form an RNA-induced silencing complex (RISC) (3). RISC uses the attached RNA to bind to a cytoplasmic messenger RNA that has a complementary sequence to the bound RNA. After binding is achieved, RISC catalyzes the cleavage of mRNA (4). The degradation of cellular mRNA results in a dampening of protein production, equivalent to reducing the effect the gene has in the cell. RNAi thus allows the cell to control protein output, a central component of cellular function.

Lucy Li
St. Paul Academy and Summit School, MN
Teacher: Tina Barsky

Genetic limb malformations, which are the second most common type of human malformation, are sometimes caused by enhancer mutations, especially if the malformation is isolated to one limb of the body (VanderMeer & Ahituv, 2011). The effects of enhancer mutations range from shortened limbs to changes in finger and toe number and are usually dominant traits. These often emerge during early stages of development, which involve cooperation between the anteroposterior, proximodistal, and dorsoventral axes (VanderMeer & Ahituv, 2011). A zone of polarizing activity, or ZPA, expresses a gene called Sonic Hedgehog, or SHH, that signals the development of the anteroposterior axis (VanderMeer & Ahituv, 2011). SHH is regulated by a widely studied enhancer called the ZPA regulatory sequence, or ZRS. ZRS is located about one million base pairs away from SHH, within the intron of a gene called limb region 1 on chromosome 7 (Visel et al., 2009).

ZRS is important to SHH because any unusual expression of SHH can cause preaxial polydactyly, in which extra fingers and toes develop next to the thumb. So far, scientists have identified thirteen point mutations in ZRS that cause human limb malformations (VanderMeer & Ahituv, 2011).

Gabrielle Ewall
Cold Spring Harbor High School, NY
Teacher: Jaak Raudsepp

During development, neural stem cells migrate throughout the body before differentiating into more specific types of neurons due to the activity of certain regulatory genes which transition on and off in a specific order. The precise timing of this mechanism is controlled by a number of processes, one of which being DNA methylation (Feng et al., 2007). During early development, the CpG site undergoes a repeated cycle of methylation and demethylation (Teter et al., 1994). Methylation of DNA blocks transcription factors from binding to the DNA thus preventing the transcription of certain genes (Watt and Malloy, 1988). Because transcription cannot occur while the CpG sites are methylated, neurogenesis and cell differentiation do not occur before the demethylation of these sites (Takizawa et al., 2001).