Fundamentals I: 11:00-12:00
Date: 9-21-2010
Professor: Pittler
Protein Synthesis I
1
Scribe: Abby Northcutt
Proof: Ashley Russell
I. Genes and Gene Mutations – Lecture III (S1)
a. Intro
II. Mutation (S2)
a. Define Mutation: not good or bad, just a change
b. Chromosome level: rearrange entire chromosomes
c. Transposable elements not a big deal in humans
III. Mutation con’t (S3)
a. What part of a gene is most likely to be affected to cause slow or over production?
i. Defect that affects promoter, enhancer, primary core promoter, etc.
ii. Thanks to Jesse for asking him to repeat this ambiguous quandary!
b. What part of a gene is most likely to impair its function?
i. Defect in actual gene for a protein (protein coding region) or in another
protein that affects the protein of interest (secondary effect)
c. People with CCR5 mutation can not get HIV = good change
IV. Mutation con’t (S4)
a. Mutant refers to what is happening at chromosome or gene level
b. Mutant could be deleterious, but really just different from the norm
V. Types of Genetics Tests Table (S5)
a. Carrier screen, prenatal test & screen will be talked about in later lecture
b. Newborn screen can find problems that can be treated immediately (routine in US)
c. Diagnostic test usually done when there is a failure to thrive to confirm diagnosis
d. Predisposition test usually works with later onset disorders (ie. Macular
degeneration)
e. Predictive test can check for disorders that are prevalent in their family (also adult
onset diseases)
VI. Mutation (S6)
a. What is a gene?
i. DNA sequence that starts at regulatory portion of the gene & shielding
from neighboring gene effects & ends with regulatory & shielding from
neighboring gene effects
1. Between these two points is the functional portion of the gene
ii. A mutation between these two points = mutation in that gene
iii. Gene can be removed and replaced with an endogenous gene from a
different organism and yield the same product
b. Don’t call humans wild type (or mutant) just common
VII. Mutation con’t (S7)
a. For humans we say haplotype instead of wildtype
b. Demonstrated in drosophila that you have to have some genetic variation between
sister chromatids or they will not thrive (will not be viable)
i. Ie. HIV resistance (environmental influence)
VIII. Somatic Mutations (S8)
a. Somatic: not passed from one generation to the next, but can be passed to cells that
divide from the infected cell
i. Cancer isn’t transmitted automatically to offspring
b. Germline: can pass on to new generations – mutations in sperm or egg
IX. Hemoglobin (S9)
a. Read Slide
X. Single Base Change in Hemoglobin (S10)
a. DNA strand that encodes the mRNA = anti-sense strand because you want to make
sense strand of mRNA to encode for protein
i. Anti-sense = CTC (DNA) & sense = GAG (RNA)
b. Mutant changes the T to an A which causes the Glu to change to Val
i. Causes Sickle Cell Anemia from a point mutations
ii. Sickled cells don’t move well through capillaries, get stuck
Fundamentals I: 11:00-12:00
Date: 9-21-2010
Professor: Pittler
Protein Synthesis I
2
Scribe: Abby Northcutt
Proof: Ashley Russell
XI. Hemoglobin Genotype Causes Sickle Cell Anemia (S11)
a. Sickling occurs in low oxygen levels & prevents many parts of the body from getting
blood
XII. Different Sites in a Gene can Mutate (S12)
a. More of a promoter type defect = Thalessemia
i. Relatively higher levels of alpha subunit
b. Heterozygous mutation = only on one chromosome
c. Homozygous mutation = on both chromosomes
XIII. Collagen (S13)
a. Affects gene expression promoters
b. Attention Dentists: diseases that affect collagen affect teeth, eyes, & many other
organ systems
c. Procollagen is cleaved by specific proteases to produce active form of collagen
XIV. Different Collagen Mutations => Distinct Disorders (S14)
a. Ehlers-Danlos = teeth
b. Stickler Syndrome = eyes
XV. Ehlers-Danlos Syndrome Photo (S15)
a. Greatly increased elasticity of oral collagen
XVI. Alzheimer Disease (S16)
a. Receptor anchored in the Golgi Apparatus membrane (transmembrane protein)
b. When the protein is not present it results in beta amaloid accumulation & plaque
formation due to mutations
XVII. Genotype to Disease Phenotype (S17)
a. Cystic Fibrosis: CFTR protein defect (Chloride Trans-regulator Protein) = channellike protein
i. One deletion is more prevalent than others
ii. Lung infection due to pseudomonous infections
b. Duchene: more susceptible to larger types of mutations ie. Deletions; may also
involve the nearby RP gene
c. We use to have to treat the phenotype, but now we can treat the genotype with gene
therapy in some cases this will address all of the phenotypes that could be expressed
XVIII. Genotype to Disease Phenotype (S18)
a. Anticipation: some genes have the ability to increase in severity through generations
b. Marfan: inflicted Honest Abe (connective tissue disorder found in log cabin
dwellers, jk)
c. Neurofibromatosis: elephant man syndrome
XIX. Spontaneous Mutation (S19)
a. In any somatic cell change in DNA sequence can occur (toxicity, radiation,
environmental effect, drug, etc.)
i. Do give some drugs to animals to induce genetic variation to study defective
genes
b. De novo is from an error in the mechanism itself (doesn’t depend on environmental
factors or mutagen)
i. These structures have the ability to change which forms tautomers which
causes problems for the enzymes that are trying to recognize the sequence
XX. Spontaneous Mutation Rate (S20)
a. This rate has nothing to do with environmental factors
b. Some sequences of DNA just make lots of mistakes
c. Most genes have a lot more junk DNA than coding (or critical) DNA so it is more
likely that the mutation will occur in the noncoding region
XXI. Mutation Rates of Genes Causing Disease (S21)
a. Non-Mendelian genetics = not due to transmission from one organism to its
offspring (not the same as somatic)
b. Fairly significant differences, but not huge differences
XXII. Mutations in Pathogens (S22)
Fundamentals I: 11:00-12:00
Date: 9-21-2010
Professor: Pittler
a.
XXIII.
XXIV.
XXV.
XXVI.
XXVII.
XXVIII.
XXIX.
XXX.
XXXI.
XXXII.
XXXIII.
XXXIV.
Protein Synthesis I
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Scribe: Abby Northcutt
Proof: Ashley Russell
Misuse of antibiotics leads to mutation
i. Genetic experiment - dangerous
Mutational Hot Spots Exist (S23)
a. Regions in genome that are more susceptible to mutation = short repetitive
sequences
b. Three types of DNA: highly repetitive, moderately repetitive, & unique
i. Unique = genes
ii. Highly repetitive exist partially just to give a location for mutations to occur
and not effect the genome
c. Palindrome: reads the same forwards & backwards
Mutations (S24)
a. Can have very short repeat segments that cause stutter or miss by the reading
mechanism
b. Repetitive type sequences are more susceptible to mutations than other sequences
Small or Large Insertion or Deletions (S25)
a. Region that makes up the hairpin will be lost when this gene segment is read =
deletion (Left Photo)
i. Polymerase can not decode region within the hairpin
b. Recombination is non-reciprocal which ends up with a duplication on one side & a
deletion on the other (Right Photo)
Mutations (S26)
a. Having an extra copy (3) is not as bad as being short a copy (1)
i. Can be selected for in some populations ie. Africa – anti-malaria
Chromosome Photo (S27)
a. See notes on slide 26
Induced Mutation (S28)
a. Not mutually exclusive
i. Can have carcinogenic mutagen or a mutagenic carcinogen
Induced Mutation con’t (S29)
a. Hamburger or hotdog processing leads to things that can be mutagenic
b. Alkylating agents can be on hotdogs or peanut butter
i. You can eat peanut butter or hotdogs, but not at the same time (just some
personal advice)
c. Peanut butter & airplanes do generate small amounts of mutagenic or carcinogenic
exposure
d. Mismatch compliment should be repaired but if it’s not it will result in mutation
e. Acridine Orange destroys the DNA bases individually – used as a chemical weapon
Ames Test (S30)
a. If you don’t put in histidine and it can not produce histidine then it can’t survive
i. If it does not mutate to be able to produce histidine it will not live
ii. More readily mutate = more mutagenic
b. If you can add back mammalian liver tissue and the rate decreases greatly the liver
does a good job detoxifying this substance which would make less mutagenic – tells
you how well the body fights this mutagenic substance
c. Radiation from tanning booths, peanut butter, etc.
Mutagen – Source Table (S31)
a. skipped
Crossed Out (S32)
a. skipped
Natural Exposure to Mutagens (S33)
a. Already talked about – skipped
i. In general don’t worry about it but try to limit exposure
Natural Exposure to Mutagens con’t (S34)
a. Alpha form = least penetrating
b. Don’t worry about Beta’s because they can be safely contained
Fundamentals I: 11:00-12:00
Date: 9-21-2010
Professor: Pittler
XXXV.
XXXVI.
XXXVII.
XXXVIII.
XXXIX.
XL.
XLI.
XLII.
XLIII.
XLIV.
XLV.
XLVI.
XLVII.
Protein Synthesis I
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Scribe: Abby Northcutt
Proof: Ashley Russell
c. Gamma = dangerous
Natural Exposure to Mutagens con’t (S35)
a. Read over slide
Sources of Radiation Exposure Table (S36)
a. Read over
Types of Mutation (S37)
a. Start Your Engines
Point Mutation (S38)
a. Read through slide
Missense Mutation (S39)
a. Missense will ALWAYS be an amino acid change
Nonsense Mutation (S40)
a. Change in amino acid from a normal codon to a premature stop codon
b. Leads to molecular drug therapy – some diseases more susceptible to this treatment
than others (ie. CF or Duchene’s)
Splice Site Mutations (S41)
a. Protein may have extra material which is deleterious
Splice Site Mutations (S42)
a. Read through slide Speed Racer style
Insertion or Deletion Mutations (S43)
a. Micro insertions/deletions
i. If it’s not a multiple of three it will produce a frameshift
1. May cause premature stop codon
ii. Even if it is a multiple of three it can cause disease
Insertion or Deletion Mutations con’t (S44)
a. Read through
Types of Mutations Tables (S45)
a. Look at the differences between these
Pseudogenes (S46)
a. Has all the features of a gene but isn’t functional
Expanding Repeats (S47)
a. If you have a codon that’s repeated multiple times, you can have early onset and
more sever phentoypes => Anticipation
b. In each generation the problem is magnified and the disease state worsens with each
generation
c. Propensity for the disease worsens in successive generation
XLVIII. End Lecture 51:05 (Slides 48 through 62 may or may not be covered at a future time)