Changes in DNA

Analogy We will be using a sentence as an analogy representing a strand of DNA. Our sentence is: The fat cat ate the wee rat.   If this sentence represents a strand of DNA, what does each word represent? What does each letter represent?

Mutations?!? Now, we’re going to look at mutations in the DNA.   When you hear about mutations, you may think about some teenage turtles or growing an extra arm, but the word mutate just means change. Let’s look at what happens when we change the sentence/DNA.

Substitution The fat cat ate the wee rat. The fat cat ate the wet rat.   What changed? What does this represent? How would this type of change affect the protein? What changed: The letter “e” changed to “t”. What does this represent: It represents a substitution of a single nucleotide in a codon. How would this type of change affect the protein: It may change one amino acid in the protein, or it may not change anything; depending upon the specific nucleotide change. For example, if AAA becomes AAG, they both still code for the same amino acid (phenylalanine).

Deletion The fat cat ate the wee rat. The fat cat att hew eer at.   What changed? What does this represent? How would this type of change affect the protein? What changed: The “e” in “ate” was deleted. This caused all the letters to shift and changed all of the remaining codons. This represents a deletion of a nucleotide that causes a change in all the remaining triplets/codons. How would this type of change affect the protein: Because all of the remaining codons are changed, it may shorten the protein or make it ineffective.

Insertion The fat cat ate the wee rat. The fab tca tat eth ewe era t.   What changed? How would this type of change affect the protein? What changed: There was a “b” inserted between the “at” of “fat”. How would this type of change affect the protein: Again, it changes everything else remaining, so it will likely make the protein shorter or ineffective.

Point Mutations vs. Frameshift Mutations The substitution example was a point mutation. These last two examples of deletion and insertion were frameshift mutations.   What’s the difference between a point mutation and frameshift mutation? Which has the most significant impact on the protein? Why? A point mutation only changes one single point/nucleotide in the DNA sequence and so, therefore, may have a smaller impact. I either causes no change in the amino acid or a change in only a single amino acid. A frameshift mutation changes all of the remaining codons in the sequence, so therefore will likely have a much larger impact because it changes the translation of the sequence.

Synonymous (“Silent”) Point Mutations What do you think a synonymous (“silent”) point mutation is? Do not cause a change in the amino acid sequence Generally, do not cause a change in the protein—however, can reduce the amount of a specific protein the cell makes or cause the structure of the protein to be changed in a manner that disrupts its functioning in the body Example: TAT changed to TAC—both still code from Tyrosine CTC changed to CTA—both still code for Leucine **You may wish to discuss with students that research is showing that even these “silent” point mutations cause changes. Scientists used to believe that synonymous point mutations were “no big deal”; however, new research is proving them wrong. Articles to consider are: http://news.sciencemag.org/sciencenow/2006/12/22-02.html http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/ucm271385.htm http://www.nature.com/scientificamerican/journal/v300/n6/full/scientificamerican0609-46.html

Inversion The fat cat ate the wee rat. The fat tar eew eht eta tac.   What changed? How would this type of change affect the protein? What changed: The last portion of the sentence was completely inverted (reversed). How would this affect the protein: It will invert the amino acid sequence so it may result in an ineffective protein.

Chromosomal Mutations What changed? How would this type of change affect the protein? This graphic represents a chromosome level duplication mutation. A portion of the chromosome is duplicated. This may result in no noticeable change; however, it is also how some cancers spread.

Chromosomal Mutations What changed? How would this type of change affect the protein? This graphic represents a chromosome level deletion mutation. A portion of the chromosome is deleted. Deletions of larger portions of a chromosome often lead to genetic disorders (ex: Duchenne Muscular Dystrophy, Cri du chat syndrome, and Spinal Muscular Atrophy) and some deletions may be fatal. (Note to students the difference between a base sequence deletion when just one or a few nucleotides are deleted vs. a chromosomal deletion in which a large portion of a chromosome is deleted.)

Chromosomal Mutations What changed? How would this type of change affect the protein? This graphic represents a chromosome level translocation mutation. This is the rearrangement of chromosomal sections with non-homologous chromosomes. Possible affects include: destroying the gene’s function; alterations in gene expression (ex. Burkitt’s Lymphoma) or creation of a hybrid gene (ex. Chronic Myelogenous Leukemia).

Non-Disjunction Ex: Trisomy 21 or Down Syndrome Sometimes, there is an error in meiosis when egg or sperm cells divide resulting in too many or too few chromosomes. How do you think this type of change would impact an organism? Causes an abnormal number of chromosomes and often results in genetic disorders (ex. Down Syndrome, Turner’s Syndrome, Triple-X Syndrome). This can also result in death of the fetus.

Mutation Impact The impact of a mutation on an individual also depends on where and when it occurs. If there was a mutation in the DNA of a zygote, how would that impact the individual? How might a mutation in a skin cell affect an individual?

Pedigree Charts Pedigree charts are like a genetic family tree. They can use family information to trace genetic conditions that have been passed along in the family (genetic conditions caused by mutations). Genetic counselors use them to help people analyze their family history and determine the probability of them having or passing on a particular condition (mutation).

Pedigree Chart Symbols Empty Square = male Empty Circle = female Filled/Darkened Square = affected male Filled/Darkened Circle = affected female Square/Circle with Slash through = deceased individual

Pedigree Chart Example Use this diagram to talk about autosomal vs. sex-linked. In this example, the number of affected males and females is almost 50/50, meaning it is autosomal, not sex-linked. If a trait is sex-linked, it will be seen in mostly males (because they have only one of each chromosome X and Y). In addition, this is a dominant trait because the original parent was affected. If the original parents are not affected, then we know the trait is recessive. Graphic attribution: By Jerome Walker (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC-BY-2.5 (http://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons