lecture 12: mutation Flashcards
What is a mutation?
Permanent change in a cell’s genome
Are mutations goal-oriented?
No, they are random in nature and any DNA sequence can be affected
What do mutations result from? (2)
- DNA damage
2. Mistakes made during cell division
What induces mutations? (2)
Induced by mutagens
- Physical agents
- Chemical agents
What are examples of mutagens that induce mutations?
Natural metabolism, UV light, H2O2
What are the 3 possible effects of mutation on organisms?
- Beneficial
- Neutral
- Harmful
What are the two scales of mutations?
- Gene Mutations
2. Chromosome Mutations
Characteristics of gene mutations? (2)
- Small scale
- Involve one gene
Characteristics of chromosome mutations?
- Large scale
- Involve several genes
What do gene mutations cause? (3)
- Base pair substitutions
- Base pair additions or deletions
- Segment duplications or deletions
What do chromosome mutations cause? (2)
- Changes to chromosome structure
2. Changes to chromosome number
Describe a gene mutation/small-scale mutation
1 original DNA —> Error in replication (base-pair mismatch) —> Cell division: one daughter cell have the right, original template & other will have a mutant (different mRNA and polypeptide produced)
What are the 4 types of structural changes to chromosomes (large-scale mutation)?
- Deletion: removes a chromosomal segment
- Duplication: repeats a segment
- Inversion: reverses a segment within a chromosome
- Translocation: moves a segment from one chromosome to a nonhomologous chromosomes
—> Changes whole regions of chromosomes which contain several genes
Does a karyotype allow us to observe small-scale mutations (gene mutations)?
No, only large-scale mutations (chromosome mutations)
Three categories of effect of mutations on organisms based on their fitness
- Beneficial mutations: increases fitness of organism
- Neutral mutations: do not affect their fitness
- Deleterious mutations (FREQUENT): decrease the fitness of the organism
most small-scale mutations are … or …
neutral or deleterious
Large-scale mutations are almost always…
deleterious
SOMETIMES mutations results in…
beneficial
What is the main effect of mutation?
- Ultimate source of genetic and trait variation in all populations
- Fuel for evolution and speciation
Are mutations considered as diseases?
No, if there weren’t mutations, there would not have any difference in traits
What important characteristic of genes result from mutation?
Alleles or genes —> different versions of one gene
How are mutations the foundation of variation in traits in a population?
Various alleles —> Various genotypes —> Expression of different genotypes results in different phenotypes (traits)
What else usually contributes to our phenotype?
Environment
What are the 2 types of mistakes in mammals and what do they result in?
- Mistakes in mitosis —> somatic mutations
2. Mistakes in meiosis —> germ-line mutations
Characteristics of germ-line mutation? (3)
- Entire organism carries the mutation
- Half of their gametes carry the mutation
- Mutation can be passed on to offsprings
Characteristics of somatic cell mutations (4)
- Only of patch of affected area
- None of gametes carry the mutation
- Produces genetic mosaic: populations of cells within the body contain different genotypes
- Usually not passed on to offspring
What are the 3 mistakes a cell can make during cell division?
- DNA replication
- Crossing over
- Anaphase
Describe a mistake made during DNA replication
Point mutations can change sequence of a gene (base-pair mismatch) —> change sequence of the polypeptide produced (mutant) —> affect its function
What might be the effect (neutral, harmful, or beneficial) of a single nucleotide substitution?
Harmful or neutral (if it’s a different amino acid, but same codon)
What might be the effect (neutral, harmful, or beneficial) of a single nucleotide deletion?
Base-pair removed —> change reading scheme —> different codon when read —> Harmful
What might be the effect (neutral, harmful, or beneficial) of a single nucleotide addition?
Base pair added —> change reading scheme and codon read —> Harmful
Describe mistake made during crossing over
Crossing over has to be done with precision that is reciprocal (need same region of gene exchanged from both chromosomes) —> If aligned incorrectly —> Unequal crossing over —> Can duplicate or delete regions within a gene
What do mistakes during anaphase cause?
Nondisjuction: mistake where chromosomes fail to be separated correctly —> results in aneuploid daughter cells with abnormal chromosome number —> nondisjuction during meiosis results in aneuploid gametes —> aneuploid gamete can produce aneuploid zygote after fertilization
What is aneuploid?
Have abnormal chromosome numbers
Will outcome differ if mistake happens in meiosis I vs when it happens in meiosis II?
Yes in meiosis I —> 2 daughter cells will have n+1 chromosome (one additional) & 2 other daughter cells will have n-1 chromosomes (missing one)
In meiosis II —> 1 has n+1, another n-1 and the 2 others have normal number (n)
What do aneuploidies/aneuploid zygotes usually lead to?
Majority of miscarriages
- Do not lead to viable offspring in humans as they do not complete development
2 types of aneuploidies?
- Trisomy: condition in which somatic cells contain 3 copies of one chromosome
- Monosomy: condition in which somatic cells contain only 1 of a chromosome pair
What is Trisomy 21 (Down’s Syndrome)?
Example of autosomal aneuploidy
- 3 copies of chromosome 21
What is Monosomy X (Turner’s Syndrome)
Example of sex chromosome aneuploidy
- Born with 1 X chromosome —> female
- Only monosomy observed in humans that gives rise to live births
2 types of sex chromosome aneuploidies
- Nondisjunction during egg development
2. Nondisjunction during sperm development
Which nondisjuction mistake occur most often?
- Trisomy 21 = most observed type of trisomy —> much more common in the smaller chromosomes (13-22)
- Most aneuploidies (other than trisomy 21) are sex chromosome aneuploidies
Autosomal aneuploidy vs Sex chromosome aneuploidy
Sex chromosome aneuploidies = much less severe consequences on development and survival
What makes nondisjunction occur?
Accidents, not genetic predisposition
What are 2 patterns in the occurence of nondisjunction?
- Maternal errors (due to error in egg vs error in sperm): accounts for most incidences of trisomy
- Maternal age (46-48): important factor in occurrence of trisomies
3 types of autosomal aneuploidies
- trisomy 21
- trisomy 18
- trisomy 13
Characteristics of trisomy 21 (Down Syndrome)?
- 1/800 frequency of # of live births
- Mental retardation, abnormal pattern of palm creases, slanted eyes, flattened face, short stature, early death
4 types of sex chromosome aneuploidies
- XXY
- XYY
- XXX
- XO
More flexibility
What is cancer?
General term for family of diseases caused by cells that are growing in an uncontrolled fashion and form dangerous masses called tumors
- Complex disease that affect array of organs
- Highly variable genetic causes resulting from mutation
- 90% do not involve mutation —> passed on to offsprings
Characteristics of tumors
Use nutriments and space needed by normal cells & disrupt function of normal tissues and organs giving rise to disease and death
2 types of tumors
- Benign: self-limited in growth, do not invade or metastasize, must be monitored as they can become malignant
- Malignant: cancerous, cells divide quickly and are invasive, can matastasize
Cancel cells display… (2)
- Uncontrolled cell division
2. Unlimited cell division
Why do cancer cells divide abnormally?
- Bc they have defective cell communication and cell cycle control system
Why do cancer cells have unlimited capacity for cell division? (2)
Bc they evade protective mechanisms that usually limit cell division:
- Senescence (aging
- Apoptosis (programmed cell death)
Normal cells only divide if… (3)
- Nutrients are available
- Growth factors are present
- Substratum (solid-support) for attachment is present (anchorage dependence —> cells anchor to surface
Normal cells stop dividing if…
they come into contact with other cells which limits cell density to a single layer (density-dependent inhibition)
Cell division defects in cancer cells do not produce single-layer of cells, they produce…
clumps of overlapping cells
Why do cancer cells lose normal limitations during cell division?
They ignore physical/chemical cues
What causes a cell to become cancerous?
Defects caused y accumulation of mutations that affect activity of proteins involved in:
- Cell cycle control
- Cell communication
- Cell senescence
- Apoptosis
- DNA repair (no repair = increases number of mutation rate in all the above)
How many mutations are needed for normal cells to become cancer cell?
Typically several mutations + many different combinations of defects
2 main types of mutations all activities of proteins
- Make go proteins overactive
2. Make stop proteins underactive
What are go proteins? (4)
- Products of proto-oncogenes
- Function in progression of cell cycle (go): tell cells to divide
- Promote cancer when activity is increased (overactive): too much division
- Transferred by cancer viruses
What are stop proteins?
- Products of tumor suppressor genes
- Function in stopping cell cycle or promoting senescence or apoptosis
- Promote cancer when activity is decreased (underactive): don’t stop division so more mutations
How does cancer develop?
Requires accumulation of SEVERAL mutations in a cell that converts normal genes into abnormal versions that produce abnormal go and stop proteins
Why is cancer prominent in later ages?
More time for more mutations
What are the 4 possible treatments of cancer?
- Surgery: if localized
- Radiation: if localized, destroy cancel cells to make them nonfunctional, make cancer cells lose their ability to repair DNA
- Chemotherapy: for metastatic tumours, damage all actively diving cells, lot of side effects
- Targeted/Personalized Therapies: specific for a individual tumour
What is “metastasize”?
Cancer cells spread in respiratory system, blood vessels and to other parts of the body —> form secondary tumours
What are some side effects of chemotherapy and why are there side effects?
Nausea: affecting the lining of digestive system
Immune suppression: less production of white blood cells
Hair loss: affect the production of hair follicle
—> Because all dividing cells are destroyed so the cells that NEED dividing would be affected too
What are targeted/personalized therapies?
The goal of cancer treatment as there is no cure for cancer
- Best option
- Find treatments that only target cancer with less damage possible to healthy cells
