Week 2 Flashcards
What is the term for increased propensity for mutations, including DNA base changes and structural alterations, in the genomic DNA?
Genomic instability
Describe the differences between Exogenous and Endogenous genetic damage.
Exogenous: involved influences from our physical environment (e.g. UV light, ionizing radiation, or carcinogens)
Endogenous: involve unintended consequence for metabolic processes (e.g. oxidation, nitrosylation, or hydolysis of DNA strands, errors in DNA replication.)
What does UV light do to DNA?
Pyrimidine bases can absorb UV light to form abnormal covalent bond called Pyrimidine dimers. These dimers distort the structure of a DNA helix, because they bond with each other rather than their counterparts.
What effects do pyrimidine dimers have?
DNA lesions that create structural defects, such as pyrimidine dimers, interfere with nuclear processes such as transcription and replication.
What are two ways endogenous sources of DNA lesions can damage individual nucleotides?
Through methylation and oxidation
True/False: ROS (reactive oxygen species) can be created from endogenous sources (i.e. many enzyme-catalyzed reactions, the mitochondrial electron transport chain, Fenton reactions, etc.)
True
How are ROS created?
When O2 accepts an extra electron, it becomes a superoxide anion O2-, an ROS.
Because ROS’s are so reactive to DNA, what sort of damage can they do?
Altering the structure of individual nucleotides, introducing covalent bonds between strands, or severing phosphodiesterase bonds leading to strand breaks.
How can pyrimidine dimers be created and why are they significant?
UV light create pyrimidine dimers. If left uncorrected, they will interfere with DNA replication and transcription.
Somatic mutations are mutations affecting tissue that is not passed on to offspring. Name an example disease that is a somatic mutation.
McCune-Albright syndrome, disease affecting bone, skin, and several endocrine tissues.
Germline mutations affect tissue uniquely designed to produce sex cells. They are inherited. Would the mutation that exhibits cafe au lait spots on skin be considered a germline mutation?
Yes, Mutation in the NF-1 gene, results in a patient with neurofibromatosis type 1, where the patient will have changes in skin pigmentation.
What is the name of the type of repair where cells can attempt to repair damaged nucleotide bases without breaking the phosphodiester bonds that hold nucleotides together?
Direct repair
What is the name of the enzyme that can break pyrimidine dimers in photo reactivation?
Photolyase enzyme
Do human possess Photolyase?
No, only plants
When do humans use direct repair mechanism?
What is the enzyme used?
To address spontaneous methylation.
Enzyme: O6-methylguanine methyltransferase (MGMT) detects and removes methyl groups.
What sort of repair will occur if the damage is just on one strand of the helix?
Use the complementary strand as a template for repair.
What repair occurs if the damage affects only a single nucleotide?
Base excision repair! (BER)
3 type of base excision repair: 1) _____ 2) _____ 3) _____
1) Introduction of uracil into DNA during replication
2) Deamination
3) Depurination (where a nucleotide loses it base entirely)
How is the process of BER, initiated? Enzyme used?
DNA Glycosylase, recognizes the damaged nucleotide and removes its base, creating an AP (apurine/apyrimidine) site.
What if the DNA lesion involves more than one nucleotide?
Nucleotide excision repair (NER) “Remove and replace” mechanism. Instead of a single base, a stretch of nucleotides containing the lesion is removed during NER.
Which phase of the cell cycle does NER primarily occur in?
G1 Phase
What type of damage does NER repair, that photolyase does in plants?
Pyrimidine dimers
How does NER differ from BER?
NER can recognize a broader range of single-strand lesions and removes an oligonucleotide instead of excising a single nucleotide.
What about when incorrect bases are incorporated into newly synthesized strands, what protein recognizes this mistake?
“Mut” class proteins recognize the mismatch and recruit endonuclease. From there, mismatch repair follows a similar strategy as NER.
What cell cycle does mismatch repair occur in?
S phase
What are the two repair mechanisms a cell will try when both strands of DNA are severed?
1) Homologous recombination (HR): uses a homologous chromosome as a template to process the severed strands.
2) Nonhomologous end joining (NHEJ): mechanism that uses a special ligase complex to directly fuse the ends of two DNA fragments.
Why is HR preferred over NHEJ?
Because NHEJ connects any two severed strands it can find (i.e the strands don’t have to be homologous) it is error prone and can result in mutations.
How do HR and NHEJ differ?
What phases do they occur in?
NHEJ is error-prone; HR restores nucleotide sequence by using a template. HR primarily occurs during S and G2 phases; NHEJ can occur in any phase.
What is the enzyme that unzips the DNA during DNA replication?
DNA Helicase
What additional phase will the DNA go through if it is damaged?
Go Phase
Can DNA Polymerase fix its own mistakes?
Yes it can act as an exonuclease, to remove and replace.
What enzyme removes the damaged base in Base Excision Repair?
Glycosylases
How many chromosomes are included in a person’s genotype?
46 chromosomes
What term describes a specific location on a chromosome?
A locus (Loci: plural)
Can a variation in alleles result in a disease?
If so, what it is considered now?
Most allelic variation is NOT related to disease. However, if it does, the allele is considered a pathogenic variant.
Explain Wildtype alleles.
Alleles that encode genes that do not cause disease and result in an otherwise healthy individual.
Homozygote vs. Heterozygote: If each chromosome in a pair has:
Homozygote: the same allele
Heterozygote: different alleles.
What term is used to describe the physical expression of one’s genes?
A phenotype
True/False: If only one allele is necessary to produce the phenotype encoded by the allele, then the condition is dominant.
True
Males are _____ for genes on the X chromosome.
Hemizygous - Individuals with only one allele for a trait.
How many mutant alleles are necessary to result in a male that displays the phenotype of an X-linked disorder?
One, regardless of whether or not the disorder is recessive or dominant.
True/False: Individuals can be carriers of an autosomal dominant disorder.
False! Any person who has one dominant allele of an autosomal dominant condition will express the disordered phenotype.
Why are males not the carriers of X-linked disorders?
They only have one X chromosome and do not have another to compensate with a wild type allele.
Is there male-male transmission in an autosomal dominant pedigree?
Yes, an affected male can transmit an autosomal dominant disorder to male and female offspring alike.
What kind of disorder does Tay-Sachs come from?
Autosomal recessive disorder (Tay-Sachs: mutated hexosaminidase A leading to build-up of gangliosides within lysosomes.)
Do pedigrees of autosomal recessive disorders typically show affected individuals in every generation?
No, a key feature of autosomal recessive pedigrees is that they often do not show affected members in every generation.
Explain what Heterozygote advantage is in terms of Sickle Cell disease and malaria.
People who are heterozygous with one HbA allele and one HbS allele will rarely have symptoms of sickle cell disease, and they have a natural protection against the most severe symptoms of malaria.
In an X-linked dominant pedigree, how often will affected males produce affected females?
100% of the time
In an X-linked recessive pedigree, how often will affected males produce affected males?
Never; males do not transmit X-linked disorders to their sons.
Which of Mendel’s laws states that an organism’s gametes (sperm or egg cells) randomly receive one of their two alleles?
Law of Segregation
Mendel’s Law of independent assortment: Inheritance of one gene does not affect the ______ of inheriting any other gene.
Probability
The exception of the law of independent assortment is ______.
Linkage
In terms of crossing over chromosomes, what is Linkage?
The tendency for genes that near one another to cross over together and thus be inherited together during meiosis
Are genes that are closer together or father part more likely to be inherited together?
Closer, due to linkage
An exception to the law of Dominance: ______, the proportion of individuals with a certain genotype that express the associated phenotype. Give an example.
Penetrance:
Ex: Familial breast cancer caused by BRCA1 gene mutation. It’s autosomal dominant, however not everyone with a BRCA1 mutation develops breast cancer.
Another exception of law of Dominance: What is expressivity?
The extent to which individuals express a phenotype.
When a homozygous red snapdragon (RR) is bred with a homozygous white (WW) one, heterozygous offspring (WR) will be pink. What is the name of the dominance shown here?
Incomplete dominance
When somebody is heterozygous with both A and B alleles, both genes are expressed. So one gene is not dominant to the other, and these people will have red blood cells with both A and B antigens. What sort of dominance is shown here?
Codominance
What is a mutation that occurs after fertilization? This generates cells that are different in genetic composition from other cells in the body, and as the embryo grows, so do to cells that are different (multiply)
Mosaicism
True/False: Germline mosaicism occurs after development of primordial germ cells.
False, it occurs before or during development of primordial germ cells.
Does Germline or somatic mosaicism affect the mosaic individual’s offspring?
Germline
Does allelic or locus heterogeneity involve genes at different locations?
Locus heterogeneity.
What is the mitochondrial matrix?
Name of the lumen surrounded by the inner mitochondrial membrane.
How many genes comprise Mitchondrial DNA (mtDNA)?
37 genes
True/False: mtDNA also use Histones.
False
