Genetics

Question 0

Haplotype

Answer 0

Combination of alleles at different loci that are transmitted together. Depends on number of recombination.

Question 1

Fragile x syndrome

Answer 1

CGG repeat…CG gets methylated and results in FMR1 gene to have reduced expression. Combo of genetic duplication and epigenetic control.

Question 2

Red green color blindness

Answer 2

Happens when there is unequal recombination. One red and gene and multiple green genes…these genes are 96 percent identical and can lead to faulty recombination. Lineup in prophase 1 meotic division inappropriately

Question 3

Does number of genes and chromosome size relate to each other ?

Answer 3

Usually…but for example chromosome 4 is large but does not have that many genes

Question 4

What are the three types of genetic variance that affect pharmacotherapy ?

Answer 4

1) proteins that affect metabolism (pharmacokinetics)
2) proteins that affect drug target (pharmacodynamics)
3) idiosyncratic adverse drug affects (interaction between drug and unique physiology of the patient)

Question 5

Butyrlcholinesterase and genetic polymorphism

Answer 5

Breaks down anticholinesterase drug succinylcholine. That is why paralysis only lasts 5-10 min
…defect in the BCHE gene causes slower breakdown. Autosomal recessive

Question 6

NAT2 and polymorphism (N-acety transferase)

Answer 6

Catalyzes acetylation of isoniazid. Homozygous recessive people are slow acylators and therefore are more prone to toxic affects due to higher drug concentration in the plasma if metabolism requires acetylation

Question 7

Cyp2d6

Answer 7

Responsible for breakdown of antidepressants, anti arrhythmias, and analgesics…ultrarapids can have up to 13 copies of this gene. Ultra Rapids Break down drug too fast and usually require higher doses of drugs. codeine is opposite because it is a PRO DRUG that metabolizes into morphine so it can result in toxic amount and vis versa.

Question 8

TPMT (THiopurine S-methyl transferase)

Answer 8

Methylates cancer drugs which inactivates them
…thiopurines have a small therapeutic index (anemia and life threatening myleosurpression)
-1/300 have polymorphism for low activity and therefore have to be given about 1/10 of the normal dose

Question 9

Warfarin

Answer 9

Thin therapeutic window
-S warfarin is 3-5 times more potent than R warfarin
-metabolized differently. S = CYP2C9 (polymorphism leads to pharmokinetics)
-R= others
Pharmodynsmics = target vitamin K reductase

Question 10

CYP2C9

Answer 10

Polymorphism that cause lower activity thus doses

Question 11

Warfarin pharmodynamic effect

Answer 11

Gene VKROC1 codes for vitamin k reductase complex one. Changes the dosage you have to give to patients

Question 12

What is the classical idiosyncratic genetic variance example ?

Answer 12

G6PD deficiency…this reduces a the amount of nadph produced therefore reduces the amount of oxidase stress the patient can take.
-nadph is necessary for the glutathione pool

Question 13

What drugs cause oxidative stress on RBC

Answer 13

Sulfamides, antimalarials, chlromanphenicol. Can cause hemolytic anemia

Relevant to G6PD

Question 14

Malignant hypothermia

Answer 14

Genetic disorder of skeletal muscle (autosomal dominant)

• results from altered ca2+ release from the sarcoplasmic reticulum
• most cases caused by defective RYR1 gene (ryanodine receptor gene) and causes unregulated release of Ca from sarcoplasmic reticulum

Question 15

What goes wrong with malignant hypothermia

Answer 15

Excessive ca2 cause lactic acidosis from anaerobic exercise.

• muscle fibers die leading to hyperkalemia and myoglobinuria
• triggered by inhalation anesthetic(halothane) or succinylcholine

Question 16

What three things can lead to polydactyl ?

Answer 16

Over expression of GLI or SHH. Disruption in hoxd13 gene

Question 17

What chromosome and part is SHH located on ?

Answer 17

Distal part of chromosome 7

Question 18

Hypertelorism?

Answer 18

Over expression of SHH that leads to mediolateral facial extension

Question 19

Smith-lemi-opitz syndrome

Answer 19

Mutation In 7 dehydrochilesterol reductase…leads to microencphaly, mesodermal issues, polydactyl

Question 20

Achondroplasia

Answer 20

FGFR3 mutation. Almost always G transversion to C. ARGININE TO GLYCINE IN FGFR3 receptor protein. Mutation is located on the transmembrane region. Hot spot because the soerm has a selective advantage to survive despite causing mutation after birth. Gain of function mutation

Question 21

Diff mutations and types of FGFR3 gene ?

Answer 21

Thanatophoric dysplasia These two are extracellular domain and SADDAN dysplasia
Achondroplasia Transmembrane domain
Hypochondroplasia tyrosine kinase

Severe to least severe

Question 22

AZFa, b , c

Answer 22

Azoospermia factor are found deleted In infertile men

Question 23

What chromosome are alpha globulin genes found on ?

Answer 23

Chromosome 16

Question 24

What chromosome are Beta genes found on ?

Answer 24

Chromosome 11

Question 25

What are three drugs used to treat sickle cell ?

Answer 25

Derepress the epigenetic methylation that caused fetal hemoglobin(more soluable) to be repressed. - 5-axacytidine(decitabine) = demethylating drug - hydroxyurea = mechanism unknown but is best drug - buytrate compounds = inhibit histone deactylation

Question 26

What sequence should you think of when you see the word sines

Answer 26

Alu sequence

Question 27

What are the three types of pseudogenes

Answer 27

1. Vestigial Lay dormant I.e. Vitamin c 2. Duplicated Not expressed I.e. Beta globulin 3. Processed pseudogenes No promoter or intron

Question 28

What are two ways that repetitive transposons can lead to disease

Answer 28

1. Jumping genes can be inserted in a critical spot in genome and disrupt the gene 2. Repetitive sequences may lead to misalignments during MEISOIS AND GENE REPLICATION

Question 29

What is the benefit of using PCR over southern blot when looking at strs and vntr

Answer 29

Don't need a large sample and can look at more than one locus at a time. Especially helpful doing paternity test

Question 30

What is thought to be the mechanism behind evolution

Answer 30

Gene duplication...because there can be a buildup of mutations that have subtle changes that aren't an issue because the original copy still works. Mutations happen quicker

Question 31

What drugs use TPMT to inactive

Answer 31

6 mercaptopurine | Azathioprine

Question 32

Holoprosencephaly

Answer 32

Mutation in SHH or the six3 gene (regulator of SHH)

Question 33

Gorlin syndrome (Neviod basal cell carcinoma)

Answer 33

Mutation in patched (Ptc) gene | -early basal cell cancer and rib defects

Question 34

Pallister hall syndrome

Answer 34

Mutation in the GLI genes | -brain tumors, polydactyl

Question 35

Rubinstein taybi syndrome

Answer 35

Mutation in the CREBB gene - broad thumbs and toes - mental disability, short stature, small head, facial features

Question 36

What chromosome are alpha globulin genes found on ?

Answer 36

Chromosome 16

Question 37

What chromosome are Beta genes found on ?

Answer 37

Chromosome 11

Question 38

What are three drugs used to treat sickle cell ?

Answer 38

Derepress the epigenetic methylation that caused fetal hemoglobin(more soluable) to be repressed. - 5-axacytidine(decitabine) = demethylating drug - hydroxyurea = mechanism unknown but is best drug - buytrate compounds = inhibit histone deactylation

Question 39

Autosomal trisomy examples

Answer 39

21 Down Syndrome 18 Edward Syndrome 13 Patau Syndrome

Question 40

Sex chromosome Aneupolidy examples

Answer 40

``` Turner syndrome (45,X) Klinefelter Syndrome (47,XXY) ```

Question 41

Down syndrome

Answer 41

Chromosome 21. Increased maternal age affects meiosis 1 no disjunction during oogenesis. Symptoms: intellectual disability, short stature, congenital heart, epicnathal folds , up slanting palpebral fissures, depressed nasal bridge single palmar crease

Question 42

Edward syndrome

Answer 42

Trisomy 18. Non disjunction during oogenesis Symptoms: clenched fist, congenital heart defects, low set ears, micrognathia, intellectual disability, microcephaly, overlapping of fingers

Question 43

Patau syndrome

Answer 43

Trisomy 13. Non disjunction during oogenesis Features: polydactyl, CLEFT LIP AND PALATE, micropthalmia, cardiac anomalies , intellectual disability due to major cleft lip issue

Question 44

Turner syndrome

Answer 44

X chromosome monosomy -short stature, webbed neck, cystic hygroma at birth (neck swelling), primary amenorrhea (no menstruation), gonadal dysgenesis, streak ovaries. Make sure there is no Y because can lead to gonadal blastoma so must remove the gondal streak. NO BARR BODY. Look in lecture

Question 45

Klinefelter syndrome

Answer 45

47,XXY - non disjunction during meiosis. - testicular atrophy - female distribution of hair, infertility - presence of a Barr body in the buccal mucosal cells