Mutation and its types
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The Amerithrax investigation followed the 2001 anthrax attacks that killed 5 people. Letters containing anthrax spores were sent to media outlets and two senators. The FBI investigation into the source of the anthrax took 7 years. Mutations are changes in DNA sequences that are present in less than 1% of a population. Mutations can range from single DNA base changes to missing or extra chromosomes. They can affect protein function and transcription. Most mutations are recessive and cause loss of function, while gain-of-function mutations tend to be dominant. Sickle cell disease was the first genetic illness understood at the molecular level. It results from a single amino acid substitution in the beta globin protein that causes
Mutation and its types
- 2. The Amerithrax Story In the weeks following the 2001 terrorist attacks in the United States, Several people, including two senators and individuals at several media outlets, received letters containing threatening messages and a mysterious white powder. Of the 22 people who opened the letters and were exposed to the contents—spores of Bacillus anthracis —five died of inhalation anthrax. The Federal Bureau of Investigation (FBI) dubbed the investigation, which took 7 years, “Amerithrax
- 3. Mutation A mutation is a change in a DNA sequence that is present in less than 1 percent of individuals in a population. “mutate” refers to the process of altering a DNA sequence. Mutations range in size from alteration of a single DNA base; to deletion or duplication of tens, hundreds, thousands, or even millions of bases; to missing or extra entire chromosomes. Mutation can affect any part of the genome, including sequences that encode proteins or control transcription; in introns; repeats; and sites critical to intron removal and exon splicing
- 4. The effects of mutation vary. Mutations may impair a function, have no effect, or even be beneficial. A deleterious (harmful) mutation can stop or slow production of a protein, overproduce it, or impair the protein’s function—such as altering its secretion, location, or interaction with another protein. Geneticists describe the effect of a mutation as a “loss of function” when the gene’s product is reduced or absent, or as a “gain of function” when the gene’s action changes in some way. Most mutations are recessive and cause a loss of function. Gain-of function mutations tend to be dominant.
- 5. Geneticists define a mutation as being present in less than 1 percent of a population and a polymorphism as being present in more than 1 percent of a population. The term mutation refers to genotype—that is, a change at the DNA or chromosome level. The familiar term mutant refers to phenotype. In a germline mutation, the change occurs during the DNA replication that precedes meiosis A somatic mutation happens during DNA replication before a mitotic cell division
- 6. The Beta Globin Gene The first genetic illness understood at the molecular level was sickle cell disease In 1904, young medical intern Ernest Irons noted “many pear- shaped and elongated forms Irons sketched this first view of sickle cell disease at the cellular level, In 1949, Linus Pauling discovered that hemoglobin from healthy people and from people with the anemia, when placed in a solution in an electrically charged field (a technique called electrophoresis), moved to different positions The difference between the two types of hemoglobin lay in beta globin
- 7. Protein chemist V. M. Ingram took a shortcut to localize the mutation in the 146-amino-acid-long beta subunit. He cut normal and sickle hemoglobin with a protein- digesting enzyme, separated the pieces, stained them, and displayed them on filter paper. Ingram identified the tiny mutation responsible for sickle cell disease: a substitution of the amino acid valine for the glutamic acid that is normally the sixth amino acid in the beta globin polypeptide chain At the DNA level, the change was even smaller—a CTC to a CAC, corresponding to RNA codons GAG and GUG
- 8. The valine at this position changes the surfaces of hemoglobin molecules so that in low-oxygen conditions they attach at many more points than they would if the wild type glutamic acid were at the site. The aggregated hemoglobin molecules form ropelike cables that bend red blood cells into rigid, fragile, sickle-shaped structures
- 10. Causes of Mutation A mutation can occur spontaneously or be induced by exposure to a chemical or radiation. An agent that causes mutation is called a mutagen Spontaneous Mutation Two healthy people of normal height may have a child with achondroplasia, an autosomal dominant form of dwarfism. How could this happen when no other family members are affected? If the mutation is dominant, why are the parents of normal height?
- 11. This is a spontaneous mutation—that is, it is not caused by a mutagen. A spontaneous mutation usually originates as an error in DNA replication.
- 12. Mutational Hot Spots In some genes mutations are more likely to occur in regions called hot spots, where sequences are repetitive. It is as if the molecules that guide and carry out replication become “confused” by short repeated sequences The increased incidence of mutations in repeats has a physical basis. Within a gene, when DNA strands locally unwind to replicate in symmetrical or repeated sequences, bases located on the same strand may pair. A stretch of ATATAT might pair with TATATA elsewhere on the same strand, creating a loop that interferes with replication and repair enzymes, increasing risk of error
- 14. Induced Mutation: Geneticists use mutagens on model organisms to infer normal gene functions, yielding many collections and insights into human health Intentional Use of Mutagens: Researchers have developed several ways to test the mutagenicity of a substance Researchers exposed human connective tissue cells growing in culture to liquefied cigarette smoke. The chemicals from the smoke cut chromosomes through both DNA strands. This is an especially damaging insult because broken chromosomes can join with each other in different ways that can activate cancer-causing genes
- 15. Accidental Exposures to Mutagens: Some mutagen exposure is unintentional. This occurs from workplace contact before the danger is known; from industrial accidents; from medical treatments such as chemotherapy and radiation; and from exposure to weapons that emit radiation.
- 16. Natural Exposure to Mutagens