Gene Mutation

From IIITM-k-wiki

This project considers three cases of DNA mutation of E-coli bacteria :

Case 1: Point Mutation –�Point mutation occur when there is an exchange of a single nucleotide for another. This can be classified into three types :

1)Silent Mutations which results in the same amino acid.
2)Missense Mutations which results in a different amino acid.
3)Nonsense Mutations which results in a stop codon.

Case 2: Insertion of a set of nucleotides

Case 3: Deletion of a set of nucleotides

1 Team
2 Abstract
3 Introduction
4 Problem Analysis
5 Review of related work
6 Solution Outline
7 Glossary
8 References

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Team

Dr. M.S. Gopinathan gopinathan@mail.iiitmk.ac.in
Dr. Venkatesh Choppella choppell@gmail.com
Nithya Sam nithya-pg5@mail.iiitmk.ac.in
Vimi Soman vimi-pg5@mail.iiitmk.ac.in

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Abstract

Cell is the �building block of life”. There is bankers life and casualty something called ”Gene”�in a cell which determines the hereditary characteristics. This is a research project which aims at doing a study on gene Mutation on the protein coding region of Escherichia Coli bacteria. Mutations can be caused by copying errors in the genetic material during cell division and by exposure to ultraviolet or ionizing radiation, chemical cavite housing mutagens, or viruses. Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens. Changes in DNA caused by mutation can cause errors in protein sequence, creating partially or completely non-functional proteins.

Each cell depends on thousands of proteins to function in the right places at the right times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. A condition caused by mutations in one or more genes is called a genetic disorder. However, only a small percentage of mutations cause genetic disorders; most have no impact on health. For example, some mutations alter a gene�s DNA base sequence but don�t change the function of the protein made by the gene.

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Introduction

A Gene is the unit of heredity in every living organism. Gene is encoded in an organism�s genome, composed of DNAor RNA, and direct the physical development and behavior of the organism. Gene is a region of DNA (or RNA, in the case of some viruses) that determines the amino acid sequence of a protein (the coding sequence) and the surrounding sequence that controls when and where the protein will be produced (the regulatory sequence). The genetic code determines how the coding sequence is converted into a protein sequence. The protein-coding regions of gene is composed of a series of three-nucleotide sequences called codons. Each codon specifies a particular amino acid to be added to the protein chain; thus gene determine the protein�s primary structure.

DNA replication is a simple and precise process that creates two complete strands of DNA (one for each daughter cell) where only one existed before (from the parent cell). Shortly before the cell begins to divide, its DNA within the nucleus is �unzipped”�by a chemical called an enzyme which breaks the hydrogen bonds between the bases. Two halves of the DNA consequently exist. The free-floating nucleotides within the nucleus begin bonding to the bases of both strands. Because A only bonds with T and C only with G, both strands form exact matches. The two are identical. Mutations are changes to the base pair sequence of genetic material (either DNA or RNA). Once propagated to the next generation, this mutation may lead to variations within a species’�population. Mutations are the results of the cells’�attempts to link building repair chemical imperfections in this process, where a base is accidentally skipped, inserted, or incorrectly copied, or the chain is trimmed, or added to.

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Problem Analysis

Figure showing Translation process

A nucleotide is a character from the set {A, G, T, U}. A gene is a sequence of nucleotides. A codon is a set of 3 nucleotides. Since there are 4 types of nucleotides, we can have at most 64 different set of codons. Each codon is mapped to one of the amino acids. More than one codons can refer to same amino acids or it may refer to STOP codon. Codons are mapped to corresponding amino acids using codon table. This process is called translation.

Proteins are large molecules that make up cells in the human body. They are long ribbons that are folded up into three -dimentional shapes. Each long ribbon is a chain of connected links called amino acids. The different kinds of amino acids are strung together in a specific sequence to form a protein ribbon. The exact Tracfone Coupons sequence of these amino acids in the protein is very important for the protein for the protein to fold up correctly and to carry out its proper function in the cell.

DNA (deoxyribonucleic acid) is the information storage system of the body. DNA is a code that contains instructions telling the cell how to make all of its proteins. There is a separate DNA code (a gene) corresponding to each protein that is made by the cell. Like proteins, DNA molecules are also long ribbons. They store instructions for making the protein ribbons. Each protein is a chain of amino acids, and each DNA molecule is a chain of connected nucleotides.

Proteins are made by machines called ribosomes, which read the DNA code and translate it into a chain of amino acids to form a protein. The ribosome reads each set of three nucleotides in the DNA and determines Proteins are made by machines called ribosomes, which read the DNA code and translate it into a chain of amino acids to form a protein. The ribosome reads each set of three nucleotides in the DNA and determines which amino acids to attach Howard Kaye Insurance together. The DNA also tells the ribosome when the protein is finished; i.e. when it should stop attaching new amino acids to the protein. Because the nucleotides are read in groups of three, it is important for the ribosome to know how to group the nucleotides. If they are grouped incorrectly, the ribosome will choose the wrong amino acids and the protein will not function.

A cell is an object that has in it many genes. These genes actually determines various characteristics and features of the cell. A cell undergoes division to produce two daugther cells.

Figure showing cell division

During cell division, even the nucleotide sequence gets replicated identically(general case). So at the end of cell division, we get two cells each having the similar genes. Cell division typically results into two similar cells, unless it has undergone some kind of mutation. The mutations may cause some defects in the protein sequence. Defects in the protein can be mild or severe depending on the type of mutation.

Mutation could be due to affect of UV rays or due to influence of mutagens. A mutagen is a sequence of nucleotides. Typically, a mutagen is much smaller than a gene.

We can classify mutation into 3 types based on its nature -

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Point Mutation.
Mutation due to insertion.
Mutation due to deletion.

Mutation where in the gene sequence is affected at just a point is called point mutation. In this case one of the nucleotides in the sequence is being replaced by some other nucleotide. This could be under the influence of UV rays or some other similar substances. Point mutation can be further classified as - silent, missense or nonsense based on the output of mutation.

1. Silent mutation is the case where the new nucleotide series obtained results in the same amino acid. As mentioned before, more than one codons may refer to same amino acid, change in codon sequence may not change the resulting amino acid. Since the working of amino acid is unaffected or rather change in functionalities is silent, this process

of mutation is called silent mutation.

2. Missense mutation is the case where due to alteration in one of the nucleotides of a codon, a different amino acid itself is produced. It may or may not serve the purpose of the amino acid, which was

supposed to be generated.

3. A NONSENSE or STOP mutation occurs when the protein chain stops prematurely. This mutation is caused by a mistake in the DNA that prevents the attachment of new amino acids to the protein. This is a severe defect because much of the protein is missing, so the protein

cannot function correctly.

A frameshift mutation occurs when all of the amino acids in the protein, after a certain point, are wrong. This mutation is caused by an insertion or deletion of one or more nucleotides in the DNA. Inserting or deleting a set of nucleotide means that we can no longer group the nucleotide sequence into sets of three. Hence every set of three after the insertion or deletion is incorrectly grouped. This is a severe defect because much of the protein is

wrong and the protein cannot function correctly.

To understand how a frameshift works, and why its effects can be dramatic, consider an analagous example in English:

THE DOG ATE THE CAT WHO ATE THE RAT
Now let�s insert an �R”�after the first G:
THE DOG RAT ETH ECA TWH OAT ETH ERA T

You can see how everything after the insertion has now been changed, and why frameshifts are sometimes called gibberish mutations. A SPLICE-SITE mutation occurs when a sizeable section of the protein is missing.

Splice-site mutations can range from mild to severe, depending on which section of the protein is missing.

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Review of related work

Computer simulation of cancer growth[1]

This research results a math model to predict tumor behavior. The model is a series of mathematical equations that drive computer simulations of tumor growth and also suggests that the microenvironment around tumor cells determines the tumor�s ultimate cellular makeup and invasive potential and the math model is similar to the ones used to redict the weather.
Visualizing the Random, Rare, and Jackpot Nature of Genetic Mutations This project explores the random, rare, and jackpot nature of genetic mutations. It is a visual manifestation and expression of the potential for a mutation to occur, which is embedded in every juncture of replication.

Random nature refers to the outdoor fountains idea that mutations can spontaneously occur by chance during reproduction of a DNA sequence.
Rare nature refers to the relatively small probability of such a chance to occur.
Jackpot distribution refers to the notion that the original �spontaneous”�mutation is passed down to successive generations, causing an accumulation of that mutation within the population.

Visualizing the Random, Rare, and Jackpot Nature of Genetic Mutations[2]

This project explores the random, rare, and jackpot nature of genetic mutations. It is a visual manifestation and expression of the potential for a mutation to occur, which is embedded in every juncture of replication.

Random nature refers to the idea that mutations can spontaneously occur by chance during reproduction of a DNA sequence.
Rare nature refers to the relatively small probability of such a chance to occur.
Jackpot distribution refers to the notion that the original spontaneous mutation is passed

down to successive generations, causing an accumulation of that mutation within the population.

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