Bioinformatics: Questions and Answers

Bioinformatics: Questions and Answers

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Topic 1: Navigating and Understanding NCBI Database
In a few sentences, explain why bioinformatics is such an important discipline for understanding gene structure and function.
Bioinformatics is very update with the information about the gene structure and function. It can locate a gene within a sequence as well as predict the structure and or function of a particular gene. By applying bioinformatics to understand different biological processes, it allows a more global perspective in design, to test hypotheses about a gene or a protein and as well as allowing us the ability to take advantage of upcoming technology.
How many exons does the ERS1 estrogen receptor contain?
ERS1 contains 10 exons.
What does the ATG code for and what is the role of the ATG?
ATG codes for start and the role of ATG is to start the translation process of the gene.
The sequence of the stop codon is TGA. What is the role of the stop codon?
The role of the stop codon is to stop the translation process of the gene.
What does CDS stand for? What is the difference between the gene and the CDS?
CDS stands for coding DNA sequence. CDS refers to the portion of the DNA sequence that is translated i.e. coding sequence.
CDS are the portion of a gene’s DNA which is composed of exons, that codes for a protein. The gene is a locatable region of genomic sequence composed of nucleic acids, that code for mRNAs.
What is the function of the polyA-signal?
The function of the polyA_signal is to dissociate the ribosome that is translating the gene, adds a PolyA tail to cut transcription and add on a long chain of adenine nucleotides to increase the stability of a molecule.

Topic 2: Understanding Gene Function
Why are the UTRs important components of an mRNA sequence?
UTRs are an important component of an mRNA sequence because they are involved in regulation and stability of translation.

Why are ORFs important and what is the consequence of a STOP codon inserted into a protein coding sequence?
ORFs (open reading frame) are important because it is located before the transcription termination point which is beyond the translation stop codon. If a stop codon were to be inserted into a protein coding sequence then transcription would cease and an incomplete protein would be made which could either be harmful or harmless.

What is post-translational modification?
Post-translated modification is when proteins are being modified after they're made, being either activated or inactivated.

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Where is your gene located in the genome, how many exons and introns does it have?
The coagulation factor VIII gene also known as F8, is located at q28 (reverse strand). It consist of 26 exons and 25 introns.

List the predicted functional domains for your gene – briefly describe what one of these domains contributes to the function of the protein (100 words).
The F8 gene has seven domains;
low complexity
. intrinsic factor
. low complexity region
pfam: Cu-oxidase_3
. multi-copper oxidase
pfam: Cu-oxidase
. multi-copper oxidase
coiled coil (region)
. intrinsic factor
FA58C
. carbohydrate binding domain
pfam: Cu-oxidase_2
. multi-copper oxidase
pfam: F5_F8_type C
. responsible for phosphatidylserine binding, essential for activities
. this domain contributes to the function of the gene

Is your gene highly conserved between species? What species did you compare with and what was the level of homology? What can multi-species alignment of a gene tell you about its conservation?

The gene F8 is highly conserved between species due to the function being to important to change, it has an essential role in the body .
I compared the human gene to that of the gorilla and the mouse. Both species had a E-value of 0.0 indicating that the gene sequence is quiet similar. For the gorilla, there were a few conservative and non conservative changes to the sequence whereas for the mouse they were more conservative and nonconservative changes in the sequence but it still remained similar to that of the human gene.




Topic 3: Physiological Roles of Gene Function
Briefly describe the function of ESR-1, explain what its ligand is and what it does in the cell ( max.100 words).
ESR-1 encodes for an estrogen receptor which is important for hormone binding, DNA binding (binds to DNA to regulate different gene activity), and activation of transcription. The ESR-1 is located in the nucleus where it configures a homodimer or a heterodimer with the estrogen receptor 2. Both estrogen and its receptors are crucial for sexual development, reproductive functions, as well as having a role in other tissues, for instance, bone. They are also associated with many pathological processes such as breast cancer, endometrial cancer, and osteoporosis.

Use BioGPS to perform a search for your gene, in what tissues is it most highly expressed? Does this give you any insight into the physiological role of your gene? Why is understanding the tissue-specific abundance of gene expression important to understanding its biological role?
The coagulation factor VII gene is expressed in all tissue types but it’s highly expressed in the pineal gland as well as the prefrontal cortex. This information allows use to see that this gene is essential for every tissue due to its normal function of being a blood clotting protein. So, by understanding the tissue-specific abundance of a gene, it allows us to understand it's biological role because if you know where the gene of interest is expressed, you can comprehend its specific role.

For your chosen gene write 150-200 words (excluding references) describing the normal function of that gene (what it does) in any physiological process that you like. Don’t forget to reference your work. A PubMed search for your gene might be useful.
The coagulation factor VII gene encodes for a protein known as F8 which is a blood clotting protein (Genetics Home Reference, 2014). This protein is mainly produced by sinusoidal cells in the liver and endothelial cells located on the outside of the liver, throughout the body (Genetics Home Reference, 2014). This protein is bound to a molecule known as von Willebrand factor while circulating in the bloodstream in its inactive form (Genetics Home Reference, 2014). Once an injury to the blood vessels occurs, the coagulation factor VII protein is activated and disconnects from the von Willebrand factor (Genetics Home Reference, 2014). Once separated, the active protein combines to another coagulation factor known as IX (Genetics Home Reference, 2014). This interaction generates a chain of additional chemical reactions that help to form the blood clot (Genetics Home Reference, 2014). This blood clot seals off the injured blood vessels, preventing any further loss of blood from the body (Genetics Home Reference, 2014).



Topic 4: Genes and Disease Processes
Write 100-150 words describing the role of ESR1 in a disease process.
Estrogen receptor 1 is a key factor in many diseases. In breast cancer ESR1 plays an important role in the progression of this cancer. It has been noted that many cancers start out as estrogen dependent and express this receptor. Estrogen receptor signaling is suggested to be complex, involving extranuclear actions and co-regulatory proteins. ER-coregulatory proteins are tightly regulated under the normal conditions with miss expression primarily recorded in cancer (Roy, 2011). The ER-coregulatory proteins have the potential to be expressed differently and their functions may alter which can lead to cancer. By this gene being altered and expressed differently can lead to other genes such as PEL1 to be activated (Roy, 2011). Not only can estrogen receptors activate other genes, they are associated with growth factor receptors such as HER2, this interaction play a huge role in cytoskeleton reorganization. The disregulation of HER2 in breast cancer cells enhances the expression of an isoform of MTA1, which promotes the cytoplasmic sequestration of the estrogen receptor (alpha) (Roy, 2011). Overall the deregulation of estrogen receptors co-regulators has potential to promote metastasis of breast cancer which can be fatal.
For your chosen gene write 100 - 150 words (excluding references) describing the role of your gene in a disease process. Don’t forget to reference your work.
The coagulation factor 8 gene gives instructions for making a protein called factor VII (Genetics Home Reference, 2014). This protein binds to a molecule known as von Willebrand factor while circulating in the bloodstream in its inactive form (Genetics Home Reference, 2014). Once activated the factor VII forms a blood clot in order to seal off the damaged blood vessels (Genetics Home Reference, 2014). Mutations such as deletions, insertions, or inversions can occur which can alter the protein, creating an abnormal version or it can reduce the amount of the protein produced (Genetics Home Reference, 2014). As a result, once an injury occurs, blood clots can no longer form properly which can lead to continuous bleeding (Genetics Home Reference, 2014).




References
Genetics Home Reference, (2014) ESR1. Retrieved from
http://ghr.nlm.nih.gov/gene/F8
Genetics Home Reference, (2014) F8. Retrieved from
http://ghr.nlm.nih.gov/gene/ESR1
Genetics Home Reference, (2014) Hemophilia. Retrieved from
http://ghr.nlm.nih.gov/condition/hemophilia
Roy, S.S., Valdlamudi, R.K. (2011) Role of Estrogen Receptor Signaling in Breast Cancer Metastasis, (pp. 8) DOI: 10.115/2012/654698

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