Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic...
-
Upload
abner-sparks -
Category
Documents
-
view
217 -
download
3
Transcript of Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic...
![Page 1: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/1.jpg)
Michael Cummings
David Reisman • University of South Carolina
Mutation: The Source of Genetic Variation
Chapter 11
![Page 2: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/2.jpg)
What comes to mind when you hear the word mutation?
Often this word has a negative connotation, but mutation has made the immense variety of life on earth possible.
![Page 3: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/3.jpg)
11.1 Mutations Are Heritable Changes in DNA
Mutations are the ultimate source of all genetic variation in humans and other organisms
Mutation can occur spontaneously as a result of errors in DNA replication or is induced by exposure to radiation or chemicals
An agent that causes a mutation is called a mutagen
![Page 4: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/4.jpg)
Two Categories of Mutations
Somatic Mutations• Occur in cells of the body that do not form gametes• Occurs in mitosis• Is not transmitted to future generations
Germ-line Mutations• Occur in cells that produce gametes• Occurs during meiosis• Transmitted to future generations - inherited
![Page 5: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/5.jpg)
11.2 Mutations Can Be Detected in Several Ways
How do we know that a mutation in a gene has occurred?• Change in a phenotype that is passed on
Mutations that do not cause a change in phenotype would most likely only be detected by sequencing an individual’s DNA
![Page 6: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/6.jpg)
Identification of Dominant Mutation
Dominant mutations are easiest to detect; they are expressed in the heterozygous condition
Sudden appearance of a dominant mutation in a family can be observed in a single generation
Accurate pedigree information can be used to identify the individual in whom a mutation arose
![Page 7: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/7.jpg)
Pedigree Analysis: Sudden Appearance of a Dominant Trait
Fig. 11-1, p. 246
![Page 8: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/8.jpg)
Recessive and Sex-Linked Recessive Mutations
It is more difficult to detect a recessive mutation• Can be detected only in the homozygous condition
It is extremely difficult to identify the origin of a recessive mutation
It is even more difficult to determine the origin of a sex-linked recessive mutation• Generally will only appear in males in a family tree
![Page 9: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/9.jpg)
Pedigree: An X-Linked Recessive Trait
Queen Victoria and hemophilia
![Page 10: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/10.jpg)
11.3 Measuring Spontaneous Mutation Rates
Mutation rate • ranges from approx 1 in 10,000 to 1 in 1,000,000
copies of a gene Several factors influence mutation rate• Size of the gene: Larger genes have higher mutation
rates• Nucleotide sequence: Presence of nucleotide repeats
are associated with higher mutation rates• Spontaneous chemical changes: C/G base pairs are
more likely to mutate than A/T pairs
![Page 11: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/11.jpg)
Mutation Rates for Selected Genes
Table 11-1, p. 249
![Page 12: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/12.jpg)
Known Mutagens: Radiation
Radiation • The process by which electromagnetic energy travels
through air
In the US, the average person is exposed to about 360 mrem/year, 81% of which is from natural background sources (cosmic rays, sunlight, dirt and rocks)
A dose of 5,000 mrem is need to cause somatic cell mutations and increase susceptibility to cancer
![Page 13: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/13.jpg)
Known Mutagens: Chemicals
Base analogs structurally resemble nucleotides and are incorporated into DNA or RNA during synthesis (causes insertion of G rather than A so that an A/T base pair is converted to a G/C in the helix
Chemical modifiers directly change the bases in DNA, Nitrous acid changes cytosine into uracil, resulting in a G/C to A/T mutation
Intercalating agents generally distort the double helix, addition or deletion of a base pairs during DNA replication
![Page 14: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/14.jpg)
Exposure to Chemical Mutagens
Not in text, not included on exam questions
Aflatoxin – in peanuts Nitrophenols, anisoles, toluene – hair dyes Furylfofuramide – food additive Nitrosamines – pesticides, herbicides cigarette smoke Sodium nitrite – smoked meats PBDEs – flame retardant
![Page 15: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/15.jpg)
Types of Mutations
Point Mutations or Nucleotide substitutions • Missense mutation – replaces one amino acid with another• Nonsense mutations – an amino acid codon is changed to
a stop codon• Sense mutation – a termination codon is changed into a
one that codes for an amino acid, producing elongated proteins
• Silent mutation – no effect on phenotype
Frameshift mutations • Bases are added to or removed from DNA, causing a shift in
the codon reading frame (nucleotide changes in multiples of 3 will NOT cause a frame-shift, but very likely alter the phenotype)
![Page 16: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/16.jpg)
Hemoglobin Variants: Missense Mutations
Fig. 11-8, p. 254
![Page 17: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/17.jpg)
Sense mutations in Alpha Globin Proteins
Table 11-3, p. 255
![Page 18: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/18.jpg)
Fig. 11-9, p. 256
mRNA transcribed from the DNA
DNA TEMPLATE STRAND
Resulting amino acid sequence Arginine Glycine Tyrosine Tryptophan Asparagine
Altered message in mRNA
A BASE INSERTION (RED) IN DNA
The altered amino acid sequence Arginine Glycine Leucine Leucine Glutamic acid
Genomic analysis has revealed that deletions and insertions account for 5-10% of known mutations
![Page 19: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/19.jpg)
Trinucleotide Repeats and Gene Expansions
Trinucleotide repeats • A three base-pair repeating sequence (example:
CGGCGGCGGCGG)
Allelic expansion • Increase in gene size caused by an increase in the
number of trinucleotide sequences• Potential for expansion is a characteristic of a specific
allele
![Page 20: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/20.jpg)
Diseases due to Expanded Tri-Nucleotide Repeats
Table 11-4, p. 257
![Page 21: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/21.jpg)
Gene Expansion is Related to Anticipation
Anticipation • Onset of a genetic disorder at earlier ages and with
increasing severity in successive generations• Due to increasing number of repeats with successive
generations
![Page 22: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/22.jpg)
Anticipation of Myotonic Dystrophy
![Page 23: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/23.jpg)
11.6 Mutations and DNA Damage Can Be Repaired Not all mutations cause permanent genetic damage
Cells have enzyme systems that repair DNA• Mismatch repair – enzymes detect nucleotides that do
not base pair in newly replicated DNA; the incorrect base is excised and replaced
• Excision repair - enzymes cut out the 1-30 bases of DNA with the mistake and resynthesize the small fragment
• End-joining – when both strands of the DNA molecule are cut, proteins simply take the ends and stick them back together
![Page 24: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/24.jpg)
Rates of DNA Damage
Table 11-5, p. 258
![Page 25: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/25.jpg)
Maximum DNA Repair Rates
Table 11-6, p. 258
![Page 26: Michael Cummings David Reisman University of South Carolina Mutation: The Source of Genetic Variation Chapter 11.](https://reader035.fdocuments.in/reader035/viewer/2022062422/56649ec05503460f94bcb595/html5/thumbnails/26.jpg)
Genetic Disorders Can Affect DNA Repair Systems Several genetic disorders,
including xeroderma pigmentosum, are caused by mutations in genes that repair DNA
Fig. 11-15, p. 259