GENETIC MUTATIONS

ELIZABETH MENDOZA
NOVEMBER 2019
WHAT IS A MUTATION?

• A change or alteration of a DNA sequence

• Typically rare in a population
• Generally affects the phenotype of an individual
• Can range from a change in a single nucleotide base to larger level mutations of entire chromosomes
• Can happen in any part of the DNA sequence
• Effects of mutations vary
• Most are recessive and cause loss of function
• Dominant mutations often cause gain of function, dubbed “toxic”
(Lewis, 2008)
ABOUT MUTATIONS
 Mutations can be in just some types of cells or all cells in an individual

• Germline mutations happen when DNA is replicating before meiosis

• all cells resulting from the fertilization have the mutation
• passed to the next generation
• Somatic mutations happen during DNA replication before mitosis
• That line of cells are affected, but not the whole individual
• Spontaneous (de novo) or in response to exposure to toxins (mutagen)

(Lewis, 2008)
CAUSES OF MUTATIONS

• Spontaneous (unpredictable; random through crossing over or other variance)

• Induced through intentional use of mutagens (usually in a lab for research purposes)
• Accidental exposure to mutagens (through manmade or natural disasters, lifestyle choices, etc.)
• Natural exposure to mutagens (through natural radiation in, on, and around Earth)

 Lifestyle choices (job, hobbies, etc.), location, and genetic susceptibilities help determine chance of
mutagens causing mutations

(Lewis, 2008)
SOME TYPES OF MUTATIONS
 Mutations are classified based on what they do to and how they act on the DNA

• Point mutations – change to a single nucleotide/DNA base

• Switch (transition or transversion), addition, or deletion
• Missense mutation creates a different type of amino acid than intended
• Nonsense mutation puts in a stop codon instead of creating an amino acid
• Splice-site mutations – mutation that happens where there an exon and an intron meet (this is called a splice
site) (HHS, n.d.)
• Frameshift mutation – shift that alters the reading frame, thus altering amino acid creation
• Translocation – part of a chromosome breaks off and attaches itself to another chromosome

(Lewis, 2008; Bozeman Science, n.d.)

SOME TYPES OF MUTATIONS (CONTINUED)

• Deletions – range in size from 1 nucleotide to parts of chromosome; often results from mitosis or
meiosis
• Duplication – a piece of DNA is replicated too many times during the S Phase of mitosis
• Inversion – section of DNA is copied correctly but then transcribed backward or upside down
• Insertions – extra DNA sequence or chromosome piece is added and it alters reading frame; more
consequential if this happens during meiosis than during mitosis

(Lewis, 2008; Bozeman Science, n.d.)

DNA REPAIR

• Mechanisms are in place to help protect against most errors in DNA replication
• Some errors are fixed by enzymes
• Other times damaged cells die off
• Cancer can result from damage

• DNA polymerase and DNA damage response genes are in charge of ensuring accuracy in DNA
replication
• Mitochondrial DNA cannot repair itself

(Lewis, 2008)
DNA REPAIR (CONTINUED)
• Three types of DNA repairs in humans:
• Nucleotide excision repair
• 30 different proteins do this
• Replaces up to 30 nucleotides and removes errors resulting from various exposures
• Base excision repair
• 1-5 nucleotides repaired at once
• Focuses on errors from oxidative damage
• Mismatch repair
• Enzymes look over DNA right after replication and take out any mismatches that are found, replacing them with correct
match

 Humans can have disorders in DNA repair genes, causing mutations and increasing cancer risk

(Lewis, 2008)
CHROMOSOMAL ABNORMALITIES
 Normal human karyotypes have 46 chromosomes, in pairs
• Abnormal karyotypes happen when anything is added, missing, or changed
• Embryos with abnormalities in chromosomes usually spontaneously abort (about 50% of them)
• Embryos that continue to gestate can have one of various chromosomal abnormalities listed below
• Chromosomal abnormalizes often happen at some point in meiosis or mitosis

• Polyploidy – a complete extra set of chromosomes; can be from fertilization by two sperm or from starting fertilization with a diploid
gamete (caused by nondisjunction, when sister chromatids do not separate properly during mitosis or meiosis); most of these cases
end in spontaneous miscarriage
• Aneuploidy – when a single chromosome is missing or there is an extra chromosome; usually spontaneously aborts, but fetuses born
with these chromosomal abnormalities have various syndromes depending on chromosome affected; nondisjunction is an error
during meiosis that causes aneuploidy
• Monosomy - a chromosome missing from the pair; most cases spontaneously abort
• Trisomy – an extra chromosome is added to the pair; most cases spontaneously abort; most frequent Trisomy are 21, 18, and 13

(Lewis, 2008; Bozeman Science, n.d.; Encyclopedia Britannica, 2019)

CHROMOSOMAL ABNORMALITIES (CONTINUED)

• Structural abnormalities – a change in the structure of one of more chromosomes

• Deletion – part of the chromosome is missing; microdeletion possible
• Duplication – an extra section of DNA is replicated on a chromosome; microduplication possible
• Translocation – a piece of one chromosome is removed and transferred to another chromosome
• Inversion – a piece of chromosome has become detached, turned around, and re-attached
• Ring – a piece of chromosome broke off and formed a ring shape in the chromosome; isochromosome; meiosis
error

(Lewis, 2008; Bozeman Science, n.d.; NHGRI, 2019)

REFERENCES
Bozeman Science. (n.d.) Mutations [video file]. Retrieved from http://www.bozemanscience.com/mutations

Encyclopedia Britannica. (2019). Polyploidy. Retrieved from https://www.britannica.com/science/polyploidy

Lewis, R. (2008). Human genetics, 11th ed. New York, NY: McGraw-Hill Education.

National Human Genome Research Institute (NHGRI). (2019, November 7). Chromosome abnormalities fact
sheet. Retrieved from https://www.genome.gov/about-genomics/fact-sheets/Chromosome-Abnormalities-Fact-
Sheet

U.S. Department of Health and Human Services (HHS). (n.d.) NCI Dictionary of Genetics Terms: Splice-site
mutation. Retrieved from https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/splice-site-
mutation