Final Flashcards
What are the three “types” of diseases?
- acquired (cancer)
- infectious
- inherited
What are the 3 types of different ways that a genetic disease can be inherited?
- Autosomal
- X/Y linked
- mitochondrial
What is the difference between monogenic and polygenic?
monogenic: one gene involved (Mendelian)
polygenic: multiple genes involved
What are the consequences of mutations in coding/non-coding/regulatory regions?
coding: could affect the proteins being built
noncoding: affects amount of gene expression
regulatory: disrupt transcription factor binding sites
Define haplotype
group of closely-linked genes that tend to be inherited as a block
What are 2 reasons we would want to know what gene causes a disease?
- screening purposes
- druggable targets
What is a polygenic risk score?
provide a measure of your disease risk due to your frequency of SNPs
What are 3 biases with GWAS?
- self reporting
- location of data collection
- sample type
What is trio sequencing and how is it useful?
sequencing genome of mother, father, and offspring
- able to tell if SNP in question is inherited from a parent
What do microarrays measure for in GWAS?
hetero(yellow) /homozygosity (red, green)
whole exome sequencing better at detecting _________________ than whole genome sequencing?
novel variance
Why is exome sequencing advantageous?
Takes less time since only the usable (exons) are sequenced
What does a Manhattan plot show?
shows the significance of the associations between each genetic variant (SNP)
What is the purpose of GWAS?
identify a genotype (gene) associated with a phenotype (disease)
How was CFTR gene identified via positional cloning and Sanger sequencing?
positional cloning was able to identify which chromosome the gene was on and comparative genomic narrowed the location down
What is a current treatment for people with CF and the CFTR gene and how does it work?
Trikafta; opens up ion channel to reduce mucus
Is heterozygous or homozygous mutations worse?
heterozygous
The phenotypic severity of SNPs varies considerably, depending on the _____________ of the SNP relative to gene sequences and the genomic background of the individual
location
What is the Mendelian Inheritance of Man (MIOM)?
record of all genes that are autosomal dominant, autosomal recessive, X/Y linked, and mitochondrial
What is a katyotype?
normal number or chromosomes
What is cytogenetics?
study of chromosomes
What is aneuploidy?
abnormal number of chromosomes
What are 3 aneuploidies that we discussed in class?
- Down Syndrome (trisomy 21)
- Edwards syndrome (trisomy 18)
- Patau Syndrome (trisomy 13)
Trisomys are usually the result of ______________
non-disjunction (mispaired chromosomes during replication)
When are chromosome abnormalities typically detected?
in utero
Chromosomal instability syndromes are caused by mutations in DNA repair pathways and are associated with high rates of ________________
cancer
Cancer is a disease of the __________ in which cells divide uncontrollably
genome
What is an example of a chromosomal instability disease?
Ataxia telagiectasia
What are the three tissues of origin for cancers?
- carcinomas (90%)
- blood (9%)
- sarcoma (1%)
What tissue are carcinomas?
skin, lungs, gut
what tissue are sarcoma?
bone, fat
What is an example of acquired mutation causing cancer?
chemical
radiation
How do pathogens cause cancer?
interfere with genome
What is Helicobactor pylari?
pathogen that causes stomach cancer
mutations that lead to transformation are associated with what 3 types of genes?
- oncogenes
- tumor supressor genes
3.apoptosis related genes
what are oncogenes?
promote cell growth
what do tumor suppressor genes inhibit?
cell growth
What are the 6 hallmarks of cancer?
- self- sufficiency in growth signals
- insensitivity to anti-growth signals
- evading apoptosis
- limitless replication
- angiogensis (new blood vessels)
- mustastasis (maligenant growths)
What are driver mutations v. passenger mutations?
dirver: Mutations that provide a selective growth advantage, and thus promote cancer development
passenger: those that do not are termed passenger mutations
How does radiation treat cancer?
induces DNA damage to initiate apoptosis
How does chemotherapy treat cancer?
induces DNA damage to initiate apoptosis
How does alkylating agents treat cancer?
crosslink DNA and replication
- damaging DNA preventing replication
How does antimetabolites treat cancer?
chemically resemble nucleotides, tricking cancer cells into using its drug
How does antimicrotubules treat cancer?
inhibit microtubule function which block cell cycle
What 3 molecules are involved in triple negative breast cancer?
- estrogen receptor (ER)
- progesteron receptor (PR)
- HER2
What is Estrogen Receptors targeted with in breast cancer for treatment?
tamoxifen
What is the advantage to personalized medicine for cancer treatment?
affect healthy cells less and cells involved in cancer more
______________ chemotherapy then surgery is given for breast cancer patients but only works 50% of time
neoadjuvant
What is the purpose of single cell sequencing for tumors?
it distinguishes different cell types in tumor tissue
How does single cell sequencing work?
- disassociate single cells of tumors
- one cell per plate
- add one barcode per plate
- mix
- NGS
What is intratumor heterogeneity?
individual cells can accumulate thier own mutations
What are the 2 reasons for chemoresistance?
- chemoresistant cells were there all along
- chemo caused them
what are 3 challenges of gene therapy?
- how do we get in new DNA
- need to understand problem
- need to be very specific (safety)
What are 3 things that work best for gene therapy? (1 genes and 2 diseases)
heritable genes
monogenic disease
tissue specific disease
what is an advantage and disadvantage of in vivo gene therapy?
advantage: it’s easier to target internal organs. It’s also less complicated, since cells don’t need to be removed from a person at all.
disadvantage: they require very precise delivery of genetic material to the damaged area of the body.
What is an example of a lentivirus?
AID
What are 3 reasons lentiviruses are useful?
- infects dividing/non-dividing cells
- permanently integrates into host
- carries long pieces of DNA
what is a disadvantage of lentiviruses?
inserts randomly into genome and inserts some of its own DNA
what is an example of a lentivirus used to treat B-thalassemia (hemoglobin issue)?
Zynteglo
What are 3 advantages of Adeno-assocaited viruses? (AAV)
- non pathogenic
- infected dividing/non-dividing cells
- integrates into 1 place
what is a disadvantage of Adeno-assocaited viruses? (AAV)
can only carry small pieces of DNA
what is an example of a AAV used to treat spinal muscular atrophy by providing SMN1?
Zolgensma
Who was the first person to die from a clinical trial involving gene therapy?
Jesse Gelsinger
What disease did Jesse Gelsinger have?
OTC deficiency causes a build up ammonia
What did the death of Jesse do?
reformed informed consent
Is ex vivo or in vivo better for treating blood disorders?
ex vivo
What are CAR T cells?
T cells that detect cancer
What are CAR T cells build with?
suicide switches (injected to kills CAR T cells)
Why is forensics so concerved?
link to law
What are the 3 goals of forensics?
- establish paternity
- identify remains
- identify suspects
What is DNA finger printing?
identifying a series of short tandum repeats (STR)
What are short tandum repeats?
repeats on codons that can be used in DNA finger printing to identify people based on how many repeats they have
DNA fingerprinting uses ___________ electrophoresis
capillary
What is genetic geneology?
using publicly available genetic data base to find relatives (gold state killer)
What is a method to identify tissue?
microarrrays (look at transcriptomics)
How is measuring microbiomes useful?
each person has a unique microbiome
tell time of death
