Genetics

Question 1

mutations

Answer 1

replace, add, or delete a nucleotide base which can result in new traits
- are only relevant to evolution if they are present in the germline

Question 2

silent mutation

Answer 2

aka a synonymous mutation where the codon is different but the amino acid stays the same

Question 3

bad mutations

Answer 3

they will cause death or will be selected out as opposed to advantageous ones that will improve their fitness and will be selected for

Question 4

causes of mutations

Answer 4

are mistakes in replication or by mutagenic stress caused by chemical or physical mutagens like ionizing radiations, UV rays, ROS, or intercalating agents which cause insertions

Question 5

Eukaryotes can…

Answer 5

use several mechanisms to detect & correct mutations but aren’t 100% effective

Question 6

6 Classifications of Mutations

Answer 6

1. SNPs- 1 base pair is changed
2. Indels- insertions & deletions of 1-3 base pairs in DNA
3. VNTRs- triplets repeated
4. Transposable elements- sequences of DNA move by themselves within a genome
5. structural polymorphisms- changes in chromosome structure
6. chromosome abnormalities- altered # of chromosomes

Question 7

SNPs

Answer 7

• 1 base pair is altered
• Synonymous: Amino Acid still stays the same
• Nonsynonymous: substitution, a new AA is added, can even cause truncation of the protein
  -Ex: Sickle cell

Question 8

Indels

Answer 8

• insertion/deletion of 1-3 base pairs in DNA
• Frameshift mutation: happens in a protein coding sequence and can completely alter the whole protein sequence
• 10-fold less frequent than SNPs
• Ex: cystic fibrosis

Question 9

VNTRs

Answer 9

• Short nucleotide sequences that tandem repeat
• Slippage during replication and recombination can cause repeats to be added or removed from the VNTR which leads to alleles with different numbers of repeats
• The more repeats there are the higher the chance there is to have more repeats which causes slippage
• Microsatellites: 2-4bps and 10-30 repeats
• Minisatellites: 10-100 bps and up to 1000 repeats
• Satellites= several hundred bps which are centromeres, they are diff for all people and mutations here don’t affect the phenotype because its not coding for genes
• Used in DNA profiling for kinship analysis and forensic identification (look at satellites)
• Affected by error during replication = greater mutation rates
  -Example: Huntington’s Disease

Question 10

Transposable Elements (TEs)

Answer 10

• can create, reverse, and alter genome size so it creates genetic diversity
• about 40% of DNA is made of TEs and about ½ of DNA used to move
• HIV is an example of a retrovirus disease
• Hemophilia is example of Alu dysfunction
• 2 classes of TEs
  1. Retrotransposons
  2. DNA transposons

Question 11

Sickle Cell Anemia process

Answer 11

example of SNP
-Beta- globulin is changed from GLU to Val on the 6th AA so it goes from Hb to HbS
-Cell sickles (polymerizes) once it reaches deoxygenated blood (venous)
-This means the ion gates on the surface are affected so the electrolyte balance is off where there is high conc. of Ca+ and low conc. of K+
-The RBC dehydrates because of the K+ leakage since water follow K+
-This imbalance of Ca+ creates a hostile environment for plasmodium (malaria)
-The cell becomes sticky

Question 12

affects of sickle cell

Answer 12

-Venule occlusion leads to: microinfarction (tissue death), ischemic tissue pain (b/c of clotting), ischemic organ malfunction (b/c clotting), auto infarction of spleen because the ability to recycle RBC is shorter since they have lower lifespans now
-Shortened RBC lifespan can lead to: anemia due to loss of RBCs, jaundice b/c bilirubin accumulates in the process of hemolysis, gallstones b/c of bilirubin buildup, leg ulcers due to lack of oxygen supply b/c of anemia

Question 13

Sickle cell disease

Answer 13

homo recessive, lower life expectancy

Question 14

sickle cell trait

Answer 14

hetero, incomplete dominance, normal life expectancy but risk of crisis under certain circumstances like high altitude and exercise

Question 15

malaria and sickle cell

Answer 15

-Mosquito born disease caused by parasitic protozoan’s aka plasmodium falciparum
-Sickle cell carriers are resistant to malaria because the Ca+ increase creates a hostile environment for plasmodium and the shortened lifespan of RBCs also impairs plasmodium survival
-Malaria and sickle cell coevolved together where heterozygotes of sickle cell are resistant to malaria without severe anemia

Question 16

cystic fibrosis

Answer 16

• indel mutation
• It’s the accumulation of thick mucus secretions in the lungs, intestines, pancreas which greatly increases the risk for infection
  -most common mutation: deletion of Phe at position 508 on the CFTR gene (70% of all mutations for cystic fibrosis)
  -lifespan has been improved from 5 to 37 years
  -treatments: organ transplants (permanent solution) and releasing the mucus

Question 17

cystic fibrosis chemical process

Answer 17

-mutation in the gene that codes for CFTR Cl- channels
-normal: phosphorylation causes ATP to bind and opens Cl- channel to let Cl- out and water follows it
-mutation causes: Cl- to accumulate inside the cell so it retains lots of water so outside of the cell thick (dehydrated) mucus accumulates

Question 18

Huntington Disease

Answer 18

• VNTR mutation
• caused by the expansion of a triplet
• almost full penetrance: if you inherit the alleles you will get huntingtins (over 40 repeats)
• low rate of new mutation
  -More severe repeats = more severe disease
  -function in neuron differentiation/proliferation and thus brain development/function
  -CAG repeats: glutamine
  -The more repeats you have the earlier onset you have, avg onset 30-50
  -It develops after people typically have kids, so the trait is passed on and not selected out

Question 19

penetrance

Answer 19

what portion of people with the genotype will also express the phenotype

Question 20

anticipation

Answer 20

new generations have more severe signs and symptoms because the more repeats there are the more repeats are likely to continue to occur

Question 21

Huntington’s signs/symptoms

Answer 21

chorea (involuntary movement), paranoia/depression/mood disorders, dementia, slurred speech, unsteady gait, anticipation (shows earlier in later generations)

Question 22

Retrotransposons

Answer 22

Retrotransposons: transcribed from DNA to RNA then RNA is reverse transcribed (this step is catalyzed by a reverse transcriptase) to DNA and inserted back into genome at a new position.
- The reverse transcription is catalyzed by reverse transcriptase which is why many transposons originated from retroviruses
-most retrotransposons are of ancient origin and can no longer move while younger ones can still move and are used to mark ancestry
-retrotransposons can disrupt protein coding and regulatory regions

Question 23

retroviruses

Answer 23

are single stranded RNA viruses that replicate their genetic materiel with a reverse transcriptase that they inject into the host cell where it is reverse transcribed into DNA and inserted into the hosts DNA so now it can produce viral proteins like HIV
- Insert RNA – reverse transcriptase – into DNA – insert DNA into hosts DNA – creates new virus with reverse transcriptase RNA

Question 24

DNA transposons

Answer 24

DNA transposons: a portion of DNA is removed and the DNA intermediate is inserted into the target DNA to create a new strand of DNA

Question 25

DNA transposon and Alu
- what is an Alu
- what are 2 way’s it causes disease

Answer 25

• Alu is a short DNA sequence that was originally derived from a transposon in primates and are used to study ancestry
• Alu elements can cause disease in 2 ways
  1. Insertions: Alu inserts into specific genes, (e.g. clotting factor 9 deficiency and hemophilia)
  2. Recombination’s: homologous recombination, a recombination between Alu sequences at the wrong spot can cause a deletion, (e.g. familial hypercholesterolemia)

Question 26

Hemophilia

Answer 26

is an Alu dysfunction\
-Hemophilia A: deficiency in clotting factor8
-Hemophilia B: deficiency in clotting factor9
-Both factors are coded for on X chromosome so men most often have this disease since they only have one shot (XY) to get it right unlike women with 2 chances (XX)
-Hetero females are mildly affects, homo females severely affected
- Factor 8 or 9 deficiency disrupts the coagulation process so it can cause internal and external bleeding episodes
- Repeated bleeding into synovial joint (aka hemarthroses) can cause irritation, inflammation, scarring and reduced mobility
- A minor fall could lead to major bruising or even internal bleeding and death
- Mild hemophilia may not need treatment but its important to know incase of surgery of accidents
-Treatment: factor 8 & 9 supplements when bleeding occurs or 2-3x a week if severe hemophilia

Question 27

hemostasis steps

Answer 27

1. Vasoconstriction = reduce blood flow
2. Platelet plug temporarily blocks hole
3. Coagulation – formation of clot (this step fails in hemophilia)
4. Retraction of clot which also pulls skin back together to close hole
5. Clot degradation

Question 28

structural polymorphisms

Answer 28

• large scale chromosome rearrangements: duplications, inversions, insertions, deletions, translocations
• Have been frequent in mammalian genome evolution but impact on genetic diversity has only recently been appreciated
• chromosome 2: Most Hominidae have 24 pairs chromosomes but humans have 23 pairs because chromosomes 2 had end to end fusion of two ancestral chromosomes because primates have acrocentric chromosomes with centromere close to the ends so the short arm isn’t important if lost like in the fusion of chromosome 2 for humans it doesn’t matter or harm us
• cytochrome P450: is an enzyme with a heme cofactor and is involved with metabolic processes like drug catabolism and steroid & fat metabolism and electron transport chain
• duplication of cytochrome P450 can lead to “ultrarapid metabolizer phenotype” where they metabolize drugs rapidly which can lead to toxicity and/or treatment failure

Question 29

chronic myeloid leukemia
- acute
-chronic

Answer 29

-CML is a cancer of pluripotent hematopoietic stem cells in the bone marrow
-Chronic leukemia: regular # of cells but stem cells differentiate and divide less and later
-Acute Leukemia: stem cells divide early and produce quickly

Question 30

chronic myeloid leukemia on the genetic and cellular level process

Answer 30

-CML Cause: reciprocal translocation of DNA between ch9 and ch22
-C-abl-1
-oncogene: promotes cell proliferation normally but when mutated it enhances this ability, leading to cancer
-its active during hematopoiesis (production of blood cells) but normally its function declines
-Bcr: break point cluster region, whish codes for a protein with serine/threonine kinase activity that is constitutively expressed in cells
-This Translocation creates: 1. the Philadelphia chromosome which is a changed ch22 which show up on FISH scans 2. A fusion protein (Bcr and C-abl-1) that is constitutively expressed leading to cancer

Question 31

chromosome abnormalities

Answer 31

• aneuploidy: loss/gain of 1 chromosome
• monosomy: missing 1 chromosome
  `- trisomy: 1 extra chromosome
  -tetrasomy (not in humans): leads to miscarriage
• compatibility with life depends on the genes on the chromosome: dosage effect is crucial
• Polyploidy: gain of 1 complete haploid pair so there is a miscarriage, no cytokinesis, 2 sperm fertilize 1 oocyte
• people with an abnormal # of chromosomes have fertility issues

Question 32

conditions due to chromosomal abnormalities

Answer 32

• trisomy 13 is Patau: more likely to die than down syndrome
• trisomy 18 is Edward’s syndrome: more likely to die than down syndrome
• trisomy 21 is Down Syndrome: most likely trisomy to survive because it’s a small gene and the type of gene makes it compatible with life
• Turner syndrome: 45, X is compatible with life and these people are shorter, can survive if it’s a monosomy
• triple X syndrome: 47, XXX inactivates 2 X chromosomes
• Klinefelter syndrome: 47, XXY inactivates 1 X chromosome
• Jacob syndrome: 47, XYY there are more sex chromosomes so more SHOX genes so taller, associated with sociopathic tendencies in jail

Question 33

lyonization

Answer 33

women have double the genetic code but deal with this by Lyonization which is permanently deactivating one of the X chromosomes and is condensed into a bar body so not expressed
-this is random, early in embryonic life, decision is transmitted to all daughter cells, its because of dosage sensitive genes
-Lyonization example: calico cats are female so whichever X chromosome is deactivated wont express that color but the activated one will