Mutations of na

Gene and chromosomal mutations

1. Mutations of Nucleic Acid By: Zeravan Ali

2. Contents: What is a mutation? Normal DNA Sequence. Types of mutations. Causes of Mutations. Gene mutations affect on health and development. Significance of Mutations. References.

3. Mutations are changes in the genetic sequence, and they are a main cause of diversity among organisms. These changes occur at many different levels, and they can have widely differing consequences. In biological systems that are capable of reproduction, we must first focus on whether they are heritable; specifically, some mutations affect only the individual that carries them, while others affect all of the carrier organism's offspring, and further descendants. Mutations in gametes can be passed on to offspring of the affected individual, but mutations in body cells affect only the individual in which they occur. What is a mutation?

4. A mutation: Is any mistake or change in the DNA sequence Alters the nucleotide sequence in DNA. Can result from mutagens such as radiation and chemicals. Can produce one or more incorrect codons in the corresponding mRNA. Can produce a protein that incorporates one or more incorrect amino acids. Causes genetic diseases that produce defective proteins and enzymes. What is a mutation?

5. The normal DNA sequence produces a mRNA that provides instructions for the correct series of amino acids in a protein. Normal DNA Sequence: Correct order

6. The substitution of a base in DNA changes a codon in the mRNA. A different codon leads to the placement of an incorrect amino acid in the polypeptide. Mutation: Substitution Wrong amino acid Incorrect order

7. In a frame shift mutation, an extra base adds to or is deleted from the normal DNA sequence. All the codons in mRNA and amino acids are incorrect from the base change. Frame Shift Mutation: Incorrect amino acids

8. Mutations are changes in the genetic materials. There are two basic types of genetic mutations: Genes mutations- mutations that produce changes in a single gene. Chromosomal mutations- mutations that produce changes in whole chromosomes. Types of Mutations:

9. The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. The types of mutations include: Substitution. Insertions. Deletions. 1- Genes mutations :

10. Single base substitutions are called point mutations, recall the point mutation Glu -----> Val which causes sickle-cell disease. Point mutations are the most common type of mutation and there are two types: Transition: this occurs when a purine is substituted with another purine or when a pyrimidine is substituted with another pyrimidine. Transversion: when a purine is substituted for a pyrimidine or a pyrimidine replaces a purine. I. Substitution:

11. An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly. The insertion of additional base pairs may lead to frameshifts depending on whether or not multiples of three base pairs are inserted. Combinations of insertions and deletions leading to a variety of outcomes are also possible. II. Insertions.: Frameshifts mutations

12. A deletion mutation occurs when there a piece of DNA is removed from the sequence. The size of the DNA that is removed can vary in length, from a single base pair to an entire gene or several consecutive genes. The removal of the DNA can, again, compromise the function of the encoded protein. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s). III. Deletions:

13. Involves the chromosomal changes in the number or structure of chromosomes. Can changes the locations of genes on chromosomes, and the number of copies of some genes. There are four types: Deletion mutation. Duplication mutation. Inversion mutation. Translocation mutation. 2- Chromosomal mutations :

14. I. Deletion mutation: Deletion mutation- a piece of chromosome breaks off completely. The new cell will lack a certain set of genes. Often this is fatal to the zygote.

15. II. Duplication mutation: Duplication mutation- a chromosome fragment attaches to its homologous chromosome, which then carry two copies of a certain set of genes. A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.

16. III. Inversion mutation: Inversion mutation- the chromosome piece reattaches to the original chromosome but in a reverse position. Chromosome segment breaks off and then reattaches in reverse orientation to the same chromosome.

17. IV. Translocation mutation: If the piece reattaches to a nonhomologous chromosome a translocation mutation results. Translocations are chromosome mutations in which chromosome segments, and the genes they contain, change positions. Translocations can occur within a chromosome (intrachromosomal) or between chromosomes (interchromosomal). In an intrachromosomal translocation, a segment breaks off the chromosome and rejoins it at a different location.

18. Causes of Mutations: 1. Errors in DNA Replication: On very, very rare occasions DNA polymerase will incorporate a noncomplementary base into the daughter strand. During the next round of replication the missincorporated base would lead to a mutation. This, however, is very rare as the exonuclease functions as a proofreading mechanism recognizing mismatched base pairs and excising them. 2. Errors in DNA Recombination: DNA often rearranges itself by a process called recombination which proceeds via a variety of mechanisms. Occasionally DNA is lost during replication leading to a mutation. 3. Chemical Damage to DNA: Many chemical mutagens, some exogenous, some man-made, some environmental, are capable of damaging DNA. Many chemotherapeutic drugs and intercalating agent drugs function by damaging DNA.

19. Causes of Mutations: 4. Radiation: Gamma rays, X-rays, even UV light can interact with compounds in the cell generating free radicals which cause chemical damage to DNA. 5. DNA Repair: Damaged DNA can be repaired by several different mechanisms. 6. Direct Repair of Damaged DNA: Sometimes damage to a base can be directly repaired by specialized enzymes without having to excise the nucleotide. 7. Recombination Repair: This mechanism enables a cell to replicate past the damage and fix it later.

20. How can gene mutations affect health and development? To function correctly, each cell depends on thousands of proteins to do their jobs in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from working properly. By changing a gene’s instructions for making a protein, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder . It is important to note that genes themselves do not cause disease—genetic disorders are caused by mutations that make a gene function improperly. For example, when people say that someone has “the cystic fibrosis gene,” they are usually referring to a mutated version of the CFTR gene, which causes the disease.

21. Significance of Mutations: Most mutations are neutral (they have little or no effect). Mutations that cause dramatic changes in protein structure or gene activity can be very harmful . Mutations are a source of genetic variability in a species. Polyploidy - a mutation where an organism has an extra set of chromosomes. • Polyploid plants are often larger and stronger.

22. Drake, J. W., et al. Rates of spontaneous mutation. Genetics 148, 1667–1686 (1998). Cairns, M.J., King, A. and Sun, L.Q., 2000. Nucleic acid mutation analysis using catalytic DNA. Nucleic acids research, 28(3), pp.e9-e9. Loewe, L., 2008. Genetic mutation. Nature education, 1(1), p.113. German, J., 1983. Chromosome mutation and neoplasia (pp. 347-357). New York: AR Liss . References: