Exam 3

Question 1

How could a gene get duplicated?

Answer 1

Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

Question 2

Why does gene duplication not solve the problem of the origin of the first version of the gene?

Answer 2

What it does not solve is where did the first gene come from? Duplication only works if there is a previous existing gene to duplicate. A gene cannot duplicate something that does not exist so the question that needs exploring is where did the original gene come from and how did it get duplicated?

Question 3

In an organism, what cell lineages will enable mutations to be carried to the offspring?

Answer 3

A mutation that occurs in a germ-line cell can be passed on to the next generation. While a mutation in a somatic cell affects only the progeny of that cell and will not be passed on to the organism’s offspring

Question 4

The textbook argues that the globin gene family arose through duplication, what is an alternative explanation from a design perspective?

Answer 4

• This gene can be explained by a Designer specifically placing these genes in those organisms that need this gene. The duplication of this gene does not entirely fit within this timeline due to the fact that to get to the point of having the singular gene apparently took place 500 million years ago. A designer would know to place this gene in the genome due to the need of large amounts of oxygen holding.

Question 5

What is exon shuffling and why is it used to try to explain formation of new genes?

Answer 5

Novel genes can be created via exon shuffling. Exon shuffling is a molecular mechanism for the formation of new genes, where two or more exons from different genes are recombined between introns, yielding rearranged genes with altered functions

Question 6

What is common ancestry? What do evolutionists look at to determine how closely related two genes or organisms might be?

Answer 6

Common ancestry refers to the fact that there are similarities in the nucleotide sequences that indicated we came from similar predecessors. Common genetics is great the theory of common ancestry because it fits the narrative that we all evolved from x, y, z. This then begs the question, if common genetics is true, is it common design or common evolved ancestry?

Question 7

What are mobile genetic elements? Why do some scientists believe these came from viruses?

Answer 7

Mobile genetic elements can induce dramatic alterations in the body plan of an organism. Mobile genetic elements (MGEs) are segments of DNA that encode enzymes and other proteins that mediate the movement of DNA within genomes. Cut-and-paste transposition, replicative transposition. MGEs encode the components they need for movement. The human genome contains two major families of transposable sequences. Viruses are able to move between cells and organisms. Also, retroviruses reverse the normal flow of genetic information.

Question 8

What are some roles of mobile genetic elements?

Answer 8

• Encoding of a protein called transposase
• Antibiotic resistance genes
• Rearrange the DNA sequences of the genome in which they are embedded
• Makes up half of the human genome

Question 9

How much of the human genome is unique vs. repetitive sequences?

Answer 9

~50% is repetitive

Question 10

How much of the human genome encodes proteins?

Answer 10

1.5%

Question 11

How much do humans typically differ from one another genetically?

Answer 11

1 in every 1000 nucleotide base pairs

Question 12

What is the difference between exogenous and endogenous DNA damage factors? Give an example of each.

Answer 12

Endogenous factors (i.e. oxygen radicals, replication errors). Exogenous factors (i.e. environmental exposure).

Question 13

What happens to a cell if the DNA damage can be repaired? What happens if the damage cannot be repaired?

Answer 13

• Can be repaired: Substitution of one nucleotide pair for another as a result of incorrect base-pairing during replication or to deletion of one or more nucleotide pairs in the daughter DNA strand after DNA replication
• Cannot be repaired: These genomic correctly, these genomic errors can lead to cell death or be passed along to all daughter cells

Question 14

What is a transition mutation?

Answer 14

Pyrimidine substitutes for another pyrimidine OR a purine substitutes for another purine.

Question 15

What is a transversion mutation?

Answer 15

Pyrimidine substitutes for a purine or vice versa

Question 16

What does it mean for something to alkylate DNA?

Answer 16

Alkylating agents: add carbon containing alkyl groups that may result in a transversion mutation or may promote tautomer formation (i.e. methylguanine pairs with thymine instead of with cytosine, leading to possible transition mutations)

Question 17

What is a DNA intercalator?

Answer 17

Intercalating agents: planar molecules that can insert themselves between stacked bps, distorting the DNA double helix and causing deletion/insertion of bps (resulting in frameshift mutations); can cause chromosomes to break

Question 18

What types of mutation can result from UV damage?

Answer 18

o Strand breaks
o DNA-protein cross-linking
o Ring openings
o Base modifications
o Pyrimidine dimers (thymine dimers are most common)

Question 19

What is a translocation?

Answer 19

o Swapping of chromosome segments after a double-strand break
o In this case, repair process incorrectly fuses chromosome breaks
o Some translocations lead to cancer.

Question 20

In genetics, what is the difference between a polymorphism and a mutation?

Answer 20

• In genetics, what is the difference between a polymorphism and a mutation? (57)
  o Polymorphism is a variation in the DNA sequence that is present at an allele frequency of 1% or greater in a population.
   2 major types:
  1. Single nucleotide polymorphisms (SNPs)
  2. Insertion/Deletions (Indels)
  o A mutation is a variation in the DNA sequence that is present at an allele frequency of less than 1% in a population.

Question 21

What does the term indel mean?

Answer 21

Insertion/deletions. Insertion- insertion of an additional base pair or multiple base pairs. Deletions- one or more base pairs are lost from DNA

Question 22

What does SNP mean?

Answer 22

Single nucleotide polymorphisms. Types include Coding SNPs (cSNPs) and noncoding SNPs (ncSNPs).
Coding SNPs:
-Nonsynonymous (missense): AA substitution
-Synonymous: No AA substitution
-Nonsense: STOP codon created

Noncoding SNPs:
- Intronic regions; Exon/intron boundaries (could affect splicing)
- Promoter regions: Could alter cis/trans acting elements that regulate gene transcription or regulate gene expression
-Intergenic regions: Could affect DNA tertiary structure, interaction with chromatin and topioisomerases, or DNA replication

Question 23

What is the difference between nonsynonymous, synonymous, and nonsense SNPs in coding regions?

Answer 23

-Nonsynonymous (missense): AA substitution
-Synonymous: No AA substitution
-Nonsense: STOP codon created

Question 24

Where are some locations were noncoding SNPs could occur?

Answer 24

Noncoding SNPs can be found in the intronic regions, promoter regions, and intergenic regions

Question 25

How could indels have little impact on a protein structure even if they are within the coding region?

Answer 25

Indels are additions or deletions of nucleotide(s). Unless the length of an indel is a multiple of 3, it produces a frameshift mutation. So as long as it comes in a multiple of 3, the frameshift mutation will not occur. Frameshift indels have a significant effect on the expression of a protein.

Question 26

What is the general process or steps of DNA repair?

Answer 26

1) Recognition of damage and removal/excision of damage
2) Replacement of DNA by polymerase
3) Ligation of nick by DNA ligase

Question 27

What type of damage does base excision repair fix?

Answer 27

Oxidized bases and abasic sites. Oxidized bases: Caused by oxidative reactions. Removal and replacement of damaged base. Abasic site: Ionizing radiation, heat, spontaneous base loss.

Question 28

What type of damage does nucleotide excision repair fix?

Answer 28

Thymine dimer and pyrimidine dimers. Caused by UV light exposure. Removal and replacement of multiple nucleotides.

Question 29

What type of damage does mismatch repair fix?

Answer 29

Mismatched base:
 Caused by misincorporation during synthesis
 Some of this gets repaired during replication

Question 30

What types of damage does nonhomologous end-joining fix and homologous recombination fix?

Answer 30

o Nonhomologous end-joining
o Homologous recombination fix nicks (single-strand breaks). Caused by ionization radiation, heat, chemicals.

Question 31

What mutation leads to cystic fibrosis? What does that change about the functioning of the protein?

Answer 31

(delta)F508. A deletion in the ability to transport Chloride throughout the lung tissue. So mucus cannot be cleared out of the lungs as a result.

Question 32

What mutation leads to resistance to HIV?

Answer 32

CCR5(delta)32 this is the chemokine receptor 5, the HIV virus uses this receptor to enter the cell. If this gene is mutated, it produces the protein incorrectly and HIV can no longer enter the cell.

Question 33

What is meant by CYP polymorphisms? How can these genetic differences affect drug metabolism?

Answer 33

A polymorphism in this scenario is when a variant allele replaces one or both wild type alleles. Based on what type of allele replaces the original, it may mess with the metabolizing properties of these genes.

Question 34

What are the implications of CYP polymorphisms on drug therapies given to different ethnic populations?

Answer 34

Different ethnic populations will have varying results of the drug based on their ethnicity and if they have the certain polymorphism.

Question 35

What is precision medicine?

Answer 35

Using all available information (from genome, blood and saliva, guy microbiome, and lifestyle) to improve the precision with which patients are categorized for selection of the appropriate therapy or medical interventions

Question 36

How can genetic profiling help select the correct cancer drug therapy?

Answer 36

A targeted therapy is a drug which is designed to work directly on a single protein or enzyme with the fewest possible side effects

Question 37

How are genetic profiling studies influencing drug development?

Answer 37

The use of genetic profiling is making certain drug development more specific. With variations in genes, certain drugs need to be taken into close consideration or not used and this leads to drug development with more specificity.

Question 38

What are some factors that can contribute to variable drug response?

Answer 38

Co-medication, gender, body mass, age, environmental agents, disease, genetic factors, diet

Question 39

Define pharmacogenetics and pharmacogene

Answer 39

o Pharmocogenetics is the study of genetic influences on an individual’s response to drugs. Analysis of specific gene, or group of genes, may be used to predict responses to a specific drug or drug class.

o Pharmacogene is any gene in the response to a drug. Pharmocogenomics is the study of all genes involved in the response to a drug.

Question 40

How does CYP2D6 impact codeine metabolism? What effect does CYP2D6 polymorphisms have on drug metabolism?

Answer 40

Codeine is a commonly used opiod that must be metabolized/bioactivated into morphine for activity. CYP2D6 is the protein that performs this metabolism in the liver. Patients who deficient in 2D6 activity are biochemically unable to convert codeine into the active analog morphine.

Question 41

What does it mean for something to be a poor, intermediate, extensive, or ultrarapid metabolizer?

Answer 41

• PM: Those with two nonfunctional alleles at CYP2D6 have poor metabolism
• EM: Person with one or two functional alleles considered to have extensive metabolism
• UM: One who has duplicated or amplified active CYP2d6 considered to have ultrarapid metabolism
• Those who are deficit in this gene are unable to convert codeine into morphine
  o Likely to experience treatment failure
• Those who have UM are likely to convert codeine to morphine much quicker
  o Resulted in patient deaths

Question 42

What are some effects of genetic polymorphisms on expression of CYP genes?

Answer 42

Genetic polymorphisms of single genes, including mutations in coding sequences, gene duplications, gene deletions and regulatory mutations affect numerous drug-metabolizing enzymes.

Question 43

What are some main lessons from pharmacogenetics?

Answer 43

Many drugs that are currently available are “one size fits all,” but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects/toxic effects (called adverse drug reactions). All drug effects vary from person to person and all drug effects are influenced by genes. Most drug responses are multifactorial.