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genetics
final exam
| Question | Answer |
|---|---|
| what is a fusion gene | 2 genes merge together due to chromosomal rearrangement |
| CML fusion gene | ABL gene (9) merges with BCR gene (22) to make 9:22 |
| what is the philadelphia chromosome | 9:22, fusion gene formed by reciprocal translocation |
| what chromosome gets shorter in the philadelphia chromosome | 22 |
| two main types of genes involved with cancer | oncogene and tumor suppressor |
| oncogene aka | accelerator |
| oncogene activates | cellular proliferation |
| a mutation to oncogene causes | cells to divide uncontrollably |
| tumor suppressor gene (TSG) aka | brake |
| TSG inhibits | cellular proliferation and regulates cell cycle checkpoints |
| a mutation to TSG causes | uncontrollable growth |
| TSG details | requires 2 hits to be mutated, recessive at cellular level and gain-of-function |
| oncogene details | requires 1 hit to be mutated, dominant at cellular level, loss-of-function |
| proto-oncogene | normal genes that encode products for cell growth and division |
| proto-oncogene when mutated or over-expressed | contributes to development of cancer and called oncogene |
| Tp53 aka | guardian of the genome |
| Tp53 activates | genes involved in DNA repair or apoptosis |
| if Tp53 is mutated then, | cells move through checkpoints regardless of DNA condition |
| Tp53 is a | tumor suppressor |
| Tp53 responds to | cell stress by halting cell cycle, activating DNA repair and apoptosis, inducing senescence |
| role of cyclins and kinases in cancer | regulate the cell cycle |
| when cyclins and kinases are dysregulated, | uncontrolled division |
| cyclins activate | CDKs |
| CDKs | phosphorylate proteins to push cells into the next cell cycle phases |
| when CDKs are overactive | there is uncontrolled division |
| two hit hypotheses | TSGs need 2 mutated copes for cancer to develop because you get 2 copies of every gene so if 1 is mutated the other will step in, however if both are mutated then you lose that protection |
| inherited aka | germline |
| genetic aka | somatic, acquired |
| germline | present in every cell from birth, passed from parent to egg/sperm |
| somatic | not present in egg or sperm, occurs during lifetime |
| hardy weinberg describes | how allele and genotype frequencies stay constant from generation to generation |
| hardy weinberg assumptions | no mutations random mating equal rates of survival and reproductive success individuals don't migrate out of a population allele frequencies don't change from 1 generation to the next |
| variability | occurs if assumptions aren't met |
| dogs and variability | have a very high degree of variation - different nose shapes, sizes, colors, breeds, etc |
| a sample is in equilibrium if | allele frequency stays constant observed genotype is the expected genotype no deviations |
| if a sample is in equilibrium, | no variability |
| if a sample is not in equilibrium, | variability increases and population evolves |
| p values and equilibrium | >.05 = equilibrium <.05 = not in equilibrium |
| genetic drift | allele frequency changes by random chance, especially in small populations |
| bottleneck events | sudden, drastic changes |
| founder effect | small group leaves larger population and forms new colony |
| founder effect results in | new population with different frequency than the original population |
| when the population size is small, | random events have a huge impact |
| random mating causes | unequal allele distribution |
| phenotype | observable traits |
| mantle cell lymphoma | MCL |
| MCL genetic testing | PCR |
| COVID implications for a pt on Rituximab | symptoms last much longer because the med kills all Bcells which are needed to produce antibodies to neutralize viruses and impairs humoral immunity |
| pt on Rituximab with COVID are called | long haulers |
| what is PCR | lab technique used to amplify DNA so it can be detected, analyzed or tested |
| think of PCR like | a DNA photocopier |
| steps of PCR | denature: separate 2 strands anneal: primers stick to target sequence extension: polymerase builds new DNA |
| how many times are the PCR steps repeated | 30-40 cycles |
| PCR amplification requirements | double stranded target DNA DNA polymerase 4 deoxyribonucleoside triphosphates (ACTG's) primers!! |
| primers needed for PCR | short, single stranded sequences 1 complementary to 5' end and 1 complementary to 3' end |
| HDACs | remove acetyl groups from histone proteins, tightening the DNA and reducing gene expression |
| HDAC inhibitors (HDACi) | block HDACs, acetylation stays and chromatin opens so gene expression is increased and turns TSGs back on so cancer cells are killed |
| hallmark translocation of MCL | t(11;14) = overexpression of CCND1 |
| ROS issue with MCL | overexpression of CCND1 = rapid proliferation = increased stress = increased ROS = DNA damage and genomic instability |
| proteasome inhibitor | prevents degradation of ubiquitin-tagged proteins which leads to accumulation of pro-apoptotic factors like p53 |
| proteasome inhibitors protect | p53, cause cancer cells to die faster than normal cells |
| acute lymphocytic lymphoma | ALL |
| ALL genetic testing | TPMT genetic testing |
| TPMT | adds a methyl group to the sulfhydryl group on the drug or its metabolites, decreases the concentration of the active drug metabolites (thio-GTP and thio-dGTP), acts indirectly to decrease the effective dose of the drug |
| high TPMT | protects from toxicity, good |
| low TPMT | more drug activity = myelosuppression, bad |
| Laura (ALL case study) | homo recessive, low level of TPMT so active form of drug was not removed and lead to toxicity |
| Beth (ALL case study) | drug worked on her, normal level of TPMT (homo dominant) |
| how is ALL treated | with thiopurine |
| ALL treatments for Laura and Beth | worked on Beth did not work on Laura |
| ALL treatment has | narrow therapeutic index |
| 3 variants of TPMT | 3A, 3B, 3C |
| 3A | homo recessive, more severe results of mutations because half life is .25 (low) so drug is not broken down fast enough |
| 3B | heterozygous, half life is 6.1 lower but not terrible |
| 3C | homo dominant, major allele/wild-type, half life is 18 which is normal |
| maple syrup urine disease | MSUD |
| MSUD is | metabolic, autosomal recessive disease that occurs when there is a defect in breaking down certain AA and causes the urine to smell like maple syrup |
| what is founders effect | trait or mutation that is more common in small populations (amish) with little genetic variation |
| MSUD testing | newborn screening - heel stick to get blood |
| MSUD is diagnosed | as a newborn, within 24-48 hrs |
| MSUD diagnosis results | elevated leucine or isoleucine |
| leiden V genetic type of disorder | autosomal dominant with incomplete penetrance (skips generations) |
| leiden V disorder | blood clotting disorder caused by a mutation in the F5 gene |
| F5 gene | makes coagulation protein (factor V) |
| people with leiden V | factor V can't be normally inactivated by APC so clotting factors remain active longer than usual so there are higher chances of abnormal blood clots |
| leiden V is multifactorial: other factors that contribute are | oral contraceptives, hormone therapy, surgery, smoking, pregnancy, selective estrogen receptor modules |
| how is leiden V treated | treat the underlying causes are of the clots and use anticoagulations ONLY when needed |
| pharmocogenomics that could affect ability to treat leiden V | hetero are 3-8x more likely to develop DVT homo dom are 40-140x more likely to develop DVT |
| alzheimers disease is an | autosomal dominant disease that occurs due to the build up of misfolded proteins that results in memory loss, impaired function and behavioral/personality changes |
| genetic risk for alzheimers | APOE is the main risk factor |
| APOE has | 3 common alleles: e4, e3, e2 |
| APOe4E | strongest genetic risk factor 1 copy = 3x increased risk 2 copies = 10-15x increased risk closely related to CVD |
| early onset | closely related to down syndrome, located on chromosome 21 shift in proteolytic cleavage of APP which affects the formation of amyloid plaques through gain of function mutation |
| late onset | closely related to down syndrome, located on chromosome 21 shift in proteolytic cleavage of APP, females/fam Hx/mitochondrial variations put you at higher risk |
| pedigree red flag for alzheimers | onset before age of 65 |
| alzheimers is mutlifactorial: factors that contribute are | genetic factors, environmental exposures, lifestyle influences, age related biological changes |
| chaperone genes normal function | genes that encode proteins whose job is to assist correct folding, prevent misfolding, stabilize proteins or help degrade damaged proteins |
| when chaperone genes are impaired, | misfolded proteins accumulate more easily and contribute to AD development |
| variation is chaperone genes can | increase susceptibility, influence age of onset and affect severity |
| misfolding of proteins that contribute to AD | AB and tau |
| AB and tau and AD | misfold, aggregate and accumulate in the brain which causes neuronal dysfunction and death |
| aging and AD | aging = loss of proteostasis which means the brain is less able to refold, repair or degrade misfolded proteins |
| what causes the plaques | accumulation of misfolded proteins |
| alpha one antitrypsin | AAT |
| AAT is | a protein that protects tissues (especially lungs) from enzymatic damage |
| alpha one antitrypsin disease | genetic disorder that occurs when the body can't produce enough AAT and primarily affects the lungs and liver |
| AAT deficiency = | elastase works unchecked = destroys lung tissue |
| alpha one antitrypsin disease occurs due to | mutations in the SERPINA1 gene |
Created by:
leh195