genomics exam 3

ELSI: as a result of education on ELSI, ____ states have passed non-genetics discrimination bills. (Federal Genetic Information Nondiscrimination Act, 2008) Major ELSI with DTC personal genome services: ______ DNA is being tested? Who can see ______? who owns the ________? can the company give the data to ______ _________? who interprets results, not medically certified. genetic info doesn't just affect one ____________, it forces relatives to consider their own genetic susceptibilities. in 2013, FDA ordered 23andMe to discontinue services because there were no rules in place yet for ____________ ___________ ___________ (LDTs) or in vitro diagnostics. FDA says 23andme failed to demonstrate its service was safe or __________. DTC providers frame this as consumer ______________: we have a right to know all that we can about our own genome.

40, whose, results, data, third parties, individual, laboratory developed tests, effective, empowerment

atypical chromosomes: a human karyotype is atypical if the number of chromosomes in a somatic cells is not ________ or if the individual chromosomes have missing, extra or blocks of rearranged genetic material. atypical chromosome structure: _____________: atypical structure but the normal amount of genetic information. examples are ___________ and inversions. ____________: atypical structure that results in an excess or deficit of genetic material. examples are _________ and deletions.

46, balanced, translocations, unbalanced, duplications

chromosomes short hand formula: total chromosome number (usually _____), _____ chromosome constitution (XX or XY), atypical autosomes. normal male would have shorthand of _________. a female with trisomy 21 (down syndrome) would have shorthand of __________.

46, sex, 46XY, 47XX+21

genetic testing for children: chromosome microarray analysis: detects _______ that are associated with autism, IDD's, behavioral problems and other phenotypes. exome sequencing: sequences just the _________ region of DNA, the exons. this can reveal _______ mutations that cause disease. genome sequencing: sequences the whole genome to reveal rare mutations. these can diagnose rare disorders when there is no family history and has been very helpful. however, there are many SNPs that are not __________ ________ and it can be difficult to decide what is significant and what is not. can take a lot of time.

CNVs, coding, rare, disease causing

______ are scattered through our genome and many have no known phenotype. __________ __________ ___________ is a technique that can detect gains or losses of a chromosomal region associated with a phenotype. can affect _______ _________, or how much a gene is expressed. what causes CNVs? a process called ___________ ___________ __________ that occurs during meiosis, which is basically misalignment that causes duplications and deletion of chromosome regions.

CNVs, comparative genomic hybridization, gene dosage, non-allelic homologous recombination

the ______ genes are involved in metabolizing medications. different ________ of CYP are more efficient at processing drugs than others. cytochrome ____ have 4 broad classes of phenotypes. genetic variations in these genes can affect how an individual metabolizes different types of drugs. 1. ________ metabolizer: two variants present, one from maternal chromosome and one from paternal, produce loss of function enzymes. 2. _______ metabolizer: one variant present, the variant allele produces loss of function enzymes but the normal copy functions properly. 3. ________ metabolizer: no variant alleles and normal activity. 4. _______ ______ metabolizer: in CYP2C19 a 17 variant causes increase in enzyme activity. also happens in CYP2D6. CYP genetics is complicated because there are _____ different CYP genes. for each CYP gene, people can have different genetic variations and some can be PM for one class of drugs and the IM for another one.

CYP, alleles, P450, poor, intermediate, normal, ultra rapid, 57

hybridization molecular beacon: a small fragment of single stranded ____ folded over and hybridized with itself to form a _________ structure. one end has a fluorescent molecule called _______ attached covalently on the ______ end. the other ______ end has a ______ molecule attached. in the hairpin formation, the quencher ______ the fluorescence from the reporter, so no signal is given off. when the two components are separated from each other, it glows because no suppression. when the genetically designed hairpin hybridizes with correct DNA, it stretches and glows, indicating _____ mutation. if there is a mutation, there is no annealing and no ______.

DNA, hairpin, reported, 5', 3', quencher, suppresses, no, glow

what is 16s rRNA analysis? first step: isolate _________. PCR amplify with primers specific to a _________ _________ region of 16s rRNA. 16s rRNA is a ___________ conserved gene. used to study evolutionary relationships among microbes. you can sequence the ________ region of 16s and many sequences form multiple species can be generated at the same time from one environmental sample. 16s rRNA gene encodes for part of the _________ that is used for ____________. some regions are highly conserved, some are highly variable. primers that can anneal to many different templates are called __________ _______________.

DNA, highly conserved, evolutionary, variable, ribosome, translation, universal primers

most normal cells are "parked" in _____ phase. a set of molecules called ______ ________ signals the cell to go through the different stages of the cell cycle by ________ ______ ___________. but cancer cells escape controls on the cell cycle. cancer cells can divide rapidly often in the ________ of growth factors. they spread to other tissues through the _________ system. growth is not ________ by other cells.

G0, growth factors, signal transduction pathways, absence, circulatory, inhibited

there are several genomic based "precision" approaches to studying/detecting/treating cancer. ______ identifies risk factors, large scale sequencing of cancer genomes involves looking for similarities and differences in _________ and cancer sequences. _______ sequencing and __________ analysis can also be use. precision medicine approaches: ctDNA: _____ biopsy cancer genome sequencing: reveal ________ ________________: CAR T cells, immune checkpoint inhibitors

GWAS, healthy, exome, microarray, liquid, targets, immunotherapy

preimplantation genetic diagnosis: PGD. should do this if thinking about _______. makes sure the embryo is healthy before being implanted into mother. removes ____ cell from embryo.

IVF, one

primary methods to detect smaller mutations like ________ which are several thousand bases long: DNA _________, ________, sequencing (__________), hybridization, primer __________ and RFLP. first step in genotyping is usually always sequencing DNA which is done by ________ DNA and then doing PCR. Sanger sequencing is great for SNPs at specific locations. sequencing is the most _______ method.

SNPs, extraction, PCR, Sanger, extension, extracting, direct

multiple genetic mutations are necessary to develop cancer. cancer results from the gradual __________ of mutations in ________ cells. this is why our risk of cancer increases with _______, we are accumulating mutations

accumulation, somatic, age

cancer involves the _______ of many genes. although many of these alterations are the result of genetic mutations, some are due to changes in the ______ of _______ of the genes not the function of the gene. cancer cells have different ___________ marks than normal cells. cancer cells have extensive __________ of genes (less methylation), but _____________ of TSG __________ (over methylation). also have altered levels of _________ expression. also methylation _______ gene expression

alteration, level, expression, epigenetic, hypomethylation, hypermethylation, promoters, microRNA, suppresses

__________ is missing a single chromosome or having an extra chromosome. this results from ____________ during meiosis. _________ is having an extra chromosome and is more common, _________ is missing one chromosome. ___________ disability is a common symptoms in all aneuploidies. trisomy ____, ____ and ____ are the most common forms of autosomal aneuploidies. these chromosomes carry fewer genes than other chromosomes so extra copies of these chromosomes are better tolerated. sex chromosome aneuploids: more ______ than autosomal. arise from nondisjunction. appear phenotypically __________.

aneuploidy, nondisjunction, trisomy, monosomy, intellectual, 13, 18, 21, common, normal

3. evading cell death: cancer cells evade programmed cell death or ____________. this is a common and normal event in multicellular organisms, when cells age or become sick, they initiate programmed cell death for the health of the tissues. ______ triggers apoptosis in response to damaged DNA and other signals. many cancer cells evade apoptosis by ______ p53. p53 is a ______ and is mutated in several different tumor types.

apoptosis, p53, disabling, TSG

gene therapy: gene replacement aka gene ____________ therapy. ideal for _________ gene disorders due to loss of function mutations. adds back the _______ copy of the gene. necessary to understand basis or disease and maintain normal function. there are challenges: how to sustain ________? have to be repeated? can it be cost effective long term?

argumentation, single, functional, effect

the little block is known as the _________. each array has smaller compartments called __________. each features has millions of the same exact strand of DNA that is 25 bp long. theory says if a single stranded stretch of DNA encounters a complementary strand, it will ________ and form double stranded DNA, if one nucleotide is _________, it will not anneal. in the array are DNA sequences with one nucleotide changed. only patient DNA that matches the DNA in the array will be lit up by the biotin and the fluorescent coloring. All other DNA will be ________ away.

array, features, anneal, different, washed

two types of tumors: _________ and ____________. _________: tumors that grow in a _______ area. usually self contained with clear borders and can be __________ without affecting other tissues. _________: can invade surrounding tissues and spread via ________. the term cancer generally refers to a __________ tumor.

benign, malignant, benign, confined, removed, malignant, metastasis, malignant.

chromosomal abnormalities: chromosomal aberrations are mutations that are _____ enough to be seen by looking at chromosomes under a microscope. generally having too much genetic material has ______ effects on health than missing genetic material. most chromosomal abnormalities result in spontaneous _______. ________: filed that links chromosomal variations with phenotypes.

big, milder, miscarriages, cytogenetics

4. obtaining nutrients a growing mass of cancer cells needs oxygen and nutrients to thrive. cancer cells induce ______ _______ growth to deliver nutrients to the tumor. the process of recruiting blood vessels and inducing their growth is called ______________. establishing its own blood supply is a critical step in tumor development. angiogenesis is the growth of new blood vessels and occurs during normal development and in wound repair. it is induced but the signal gene ______ __________ growth factor (VEGF). this is also released by the tumor to stimulate growth of nearby endothelial blood vessels.

blood vessel, angiogenesis, vascular, endothelial

classification of cancer by tissue origin: __________ arise in external or internal body coverings like skin. _________ arise in supportive and connective tissue like bone. _________ and _________ arise from blood forming tissues.

carcinomas, sarcomas, leukemias, lymphomas

adult testing: ________ testing: originally offered to groups of people who have a particular ancestral background. now expanding to couples before they have __________. estimated that each person has ____ disease causing recessive mutations. a single test can detect _____ recessive diseases. two main types of susceptibility testing: _____________: an individual has an allele that is associated with an increased risk of a disease (BRCA1 mutation for example). ____________: an individual has an allele that determines/predicts they will have the disease. this type of testing basically confirms that you will develop this disease.

carrier, children, 3, 500, predisposition, predictive

4 main causes of cancer

chemicals, radiation, heredity, viruses

ctDNA: ____________ ___________ DNA. these are small fragments of DNA circulating in bloodstream. this small amount of DNA can be taken from a blood sample and _____________. it is a noninvasive approach to sequencing cancer DNA. the ______ of ctDNA in blood is related to the _______ of cancer. this is called a ________ _______ and is used for detection, staging and treatment.

circulating, tumor, sequenced, amount, stage, liquid, biopsy,

CNVs are detected by _______ __________ ___________. it combines hybridization and fluorescence. looked at CNVs of autism DNA. it finds out which starting pool has more ______________. __________ spot: more patient DNA is present and hybridized. _________ spot: hybridization is equal. _________ spot: control DNA is more hybridized and patient DNA is lacking

comparative genomic hybridization, expression, green, yellow, red

karyotypes have many uses: 1. ________ clinical diagnoses 2. _________ individuals who are at high risk for health problems (__________) 3. _________ genetic damage from exposure to ________ and mutagens 4. _____________ evolutionary relationships. the more closely related two species are, the more similar their karyotypes will be.

confirm, identify, translocation, monitor, toxins, study

tumor suppressor genes usually ______ or ______ cell division. when mutated, they lose their function (________ ________) and cannot prevent cancer. mutations to TSGs are usually ________. DNA repair genes function in _____ __________, fixing spontaneous errors made normally during the DNA replication process. some of these __________ occur in proto-oncogenes or TSGs. mutations in DNA repair genes lead to an ______________ of mutations in other genes and drastically __________ the likelihood of cancer.

control, block, absent essentials, recessive, mismatch repair, mutations, accumulation, increases

applications of pharmacogenetics: codeine: a CYP gene is responsible for converting codeine into morphine. SNPs in CYP genes can lead to ______ in activity, making them PM and codeine not work as well. other people might be U-R M and convert to morphine _______, and become at risk for opioid toxicity. antidepressants: considerable individual variation in response to antidepressants. many GWAS studies going on to identify SNPs associated with antidepressant responses. people try an average _____- ______ different prescriptions before finding the right one that helps. ______ is a serotonin receptor variant that can help predict response to different antidepressants. TPMT: thiopurine methyltransferase: important enzyme in detoxifying chemotherapy drugs. some individuals have genetic variants of TPMT that results in _____ levels of TPMT causing bone marrow _________ in leukemia patients.

decrease, quickly, 2, 3, HTR2A, low, toxicity

cancer cells are ________________. they can revert back to a ____ cell like state. cell differentiation is controlled by ______ _________. specialized/differentiated cells have a _________ to how many times they can divide, thats why cancer cells can _______ repeatedly.

dedifferentiated, stem, gene expression, limit, divide

gene therapy has two types of delivery: _________ and ________ __________. the therapeutic gene can be inserted into a _______ vehicle or it can be delivered directly to the _______ that needs it. sometimes, gene is put into own patients cells in ________. sometimes patient can use ________ _______ cells. can take own adult ______ cells and modify them then insert back into person.

direct, cell based, delivery, tissue, vitro, genetically modified, stem

personal genomics has spawned a new commercial industry that provides personal genome services. these companies are called _______ to ________ (DTC) marketers of genetic information. most companies ________ your DNA at disease associated SNPs for a fee, only one company will sequence your entire genome. genome scan vs whole genome sequencing most DTC companies offer genome scans of a limited number of SNPs. only provides insight into less than ____% of your genome. exome sequencing: provides ____% of your sequence. genome sequencing services give you the entire genome sequence but is more expensive. all of these tests can be obtained ______ medical professional input. DTC providers are not ____________ like providers of genetic tests.

direct, consumer, scan, 1, 3, without, regulated

cell free fetal DNA: _____ method to detect chromosomal abnormalities by ____________ the fetal DNA. fetal cell free DNA exists in smaller fragments. not considered ____________. fetal DNA can be detected in the blood stream. if more DNA from the paternal allele is present in the bloodstream than from the maternal allele, this indicates that the fetus may have ______ DNA than expected, which is another way to detect _______. fetal DNA comprises up to ______% of cell free DNA in maternal bloodstream.

direct, sequencing, diagnostic, more, trisomy, 13

gene therapy: any therapy that uses genes ______ or targets genes to _____ a disease. theroretically: ________ defective gene with a healthy one. applies to ______ gene disorders. in reality: not as easy to execute. adding a gene back _____ to the patient or ______ the action of a dominant negative gene.

directly, treat, replace, single, directly, stopping

what type of results do you get from a DTC provider? - ___________/trait - your ______ genotype - scientific ________ about the SNP association - ______ ______ of having SNP, most likely will be small. DTC services multiply the odds ratio of the SNP that you have with the _________ population risk to calculate your overall risk for the disease. relative risk (1.5) X avg population disease risk (10%) = your risk (_____). genome scan providers use SNPs identified in GWAS studies that are proved to be associated with a specific trait. genome scan genotypes you at each risk SNP and then calculates the risk of you developing that disease. how accurate are DTC services? not always accurate. buyers beware!

disease, SNP, information, odds ratio, average, 15%

__________: extra duplicated DNA sequences. __________: missing regions of DNA. can arise ____ ______, not inherited from parents. the bigger the duplication or deletion, the more ________ the phenotype. translocation: ____________________ chromosomes exchange parts. regions of different chromosomes are swapped. translocation _______ have no overall gain or loss of chromosomes. can result in improper gene _______ and function in carrier if breakpoint is in the middle of a gene or breaks up the _________ region. translocation carriers are usually not affected, its their children that show the phenotype of improper genetic expression.

duplications, deletions, de novo, severe, non homologous, carriers, expression, promoter,

visualizing chromosomes _____ and _____ were first used to visualize chromosomes. _________ stained more darkly. different chromosomes has unique patterns. fluorescence in _____ ____________ (FISH) is now used to visualize. smaller stretches of single stranded DNA _________ to specific and complementary sections of chromosomes and then fluoresce. entire chromosomes can be "__________" with FISH.

dyes, stains, heterochromatin, situ hybridization, hybridize, painted

DNA sequence is static, but the interpretation of the genome is ________. technical challenges to making precision medicine fueled by personalized genomics: _______ read length, improper ___________, reference _________, variant ________, consistency, standards

dynamic, short, algorithms, quality, calling

NIPT: Non-Invasive prenatal testing, using cfDNA. noninvasive, only requires blood sample. performed at 9 weeks of pregnancy, which is _________ than amniocentesis. it is highly accurate, with no risk of miscarriage. It is _____ FDA approved and can only be used for a few abnormalities right now. however, it is not diagnostic, it is just a _________.

earlier, not, screen

gene therapy vectors: there are viral and nonviral vectors, but nonviral vectors are not as ________. viruses are good at __________ cells and _______ genetic material. different viruses have different abilities to affect different cells, this is called __________. affinity for a specific cell or tissue type is determined by: cell receptors, cell _________ factors that recognize viral promoters, ability of the cell to support ________, survival in environments like the GI tract.

efficient, infecting, injecting, tropism, transcription, replication

gene therapy: ______ ______ therapy. the target is not the original gene, the target is a __________ gene or tissue. adds a gene that is supplying a needed function. appropriate for diseases in which _______ has already occured.

end run, downstream, damage

newborn genome sequencing: pilot studies ongoing to determine feasibility of sequencing ________ genome of newborns to replace newborn screening. ________ project in boston. however, it raises many _______ concerns, what will we learn, who should know, when to tell, what to do etc.

entire, babyseq, ethical

CNVs influence ____________ levels of genes. CNVs can have the biggest impact influencing _______ _________. a CNV outside of a gene can influence dosage if the CNV is of the ______ or other regulatory regions.

expression, gene dosage, promoter

Amniocentesis: ______ cells and fluid is removed from uterus and cultured in lab. ____ cells are karyotyped. fluid is tested for ________ that may indicate other genetic disorders. this can detect ______ different problems. _________ or an extra chromosome is the most common abnormality detected. performed between 14-16 weeks of pregnancy. procedure has risks, 1/1600 miscarriages. recommended to women over ____, history of miscarriages, children with birth defects or elevated serum markers. frequency of trisomy ______ exponentially with maternal age.

fetal, 20, proteins, 1000, trisomy, 35, increase

gene therapy: suppression targets __________ of _________ mutations that are dominant and cause monkey wrenches. used in cases where its not enough to just replace with a functional copy but actually have to ______ the bad copy. gene silencing happens through __________, or RNA interference, which is mediated by siRNAs. it targets _______. RNAi are small stretches of RNA that are complementary to region of gene that has the dominant mutation. _________ is an epigenetic mechanism that cells naturally use to control their own expression. this has been harnessed to use for suppression.

gain, function, stop, RNAi, mRNA, microRNAs.

germline gene therapy: alters DNA of a _________ or fertilized _____ so that all cells of the individual are changed. this is how ______ organisms are made. this is not done on humans. this is an important tool because it recreates human disease in ________ models.

gamete, egg, transgenic, animal

viruses are modified. viruses are first engineered in vitro to remove their own ______ that cause them to ________ or elicit an immune response. viral DNA that integrates into the host chromosome is stable and can be replicated but it can cause ____________ and cancer. the ideal vector: integrates into a known, ______ site in human genome or can be maintained long term outside of chromosomes. viral DNA can enter the cell and just be expressed and produce proteins and this is ideal because of more control but right now it is difficult to control. we can't always determine integration site which can cause gene activation or inactivation.

genes, reproduce, mutations, controlled

testing of the deceased: can look at _________ __________ __________. can also use OMIM to learn the ________ associated with a disease, information about a specific disease related gene or protein, disease associated genes on a ___________ of interest.

genetic testing registry, genes, chromosome

________ ________: use genetic information from an individual to predict, diagnose, screen and treat diseases. _________: ordered because of a history, symptoms, circumstances (age of parents), usually specific for a condition or set of conditions. ________: not based on a specific medical reason other than being a member of a particular population (like babies)

genetic testing, test, screen

germline vs sporadic cancer: _________ cancer: every cell in the individual has that original cancer causing mutations. this is inherited cancer. the two hit model applies to ______ cancer. ___________ cancer: a somatic cell has acquired the necessary mutations to induce tumorigenesis. this type of cancer is not inherited.

germline, germline, sporadic

1. uncontrollable growth cancer cells grow even in the absence of ________ signals. even without growth factors to _____ cell cycle and mitosis, cancer cells will go right through that checkpoint. doesn't sit in _____ like normal cells. most normal cells require an external growth signal to ___________. cancer cells make their own external growth signals. cancer cells stimulate their division by activating their signal pathways ______ an external signal. 25-50% of all cancer types have a mutation in the ____ proto-oncogene, that turns on a signal that tells the cell to divide. mutations in Ras cause the protein to become _______ in its activated form, always ______ to initiate cell growth and division. it is attached to _____ to keep growing. only ____ single point mutation is needed to mutate making it a ________ mutation.

growth, initiate, G0, replicate, without, Ras, locked, signaling, GTP, one, dominant

how does CRISPR work: consists of _____ RNA and ____ double stranded cutting protein. can be designed to cut whatever sequence you are interested in, making it __________. you can design the RNA to be complementary to whatever you want to fix. Cas9 cuts the DNA and DNA ______ mechanisms will fill in the cut DNA. CAR T cells come from _______.

guide, Cas9, precise, repair, Cas9

things genetic counselors do: track family genetic ________, _______- construction, provide information on disorders/modes of inheritance, arrange genetic ______, discuss testing ________. two main reason for genetic counseling: 1. __________ genetic counseling: presents empiric and family based risks, explains test and weighs benefits and risks of testing like amniocentesis vs cfDNA. 2. ______ ________ of inherited DNA: explain the modes of inheritance, risk of having children, predictive tests for adult onset disorders.

history, pedigree, tests, results, prenatal, family history

lots of genotyping tech is based around _____________. hybridization based approach for many genes at a time: use the _______ ________. microarray analysis is a way to explore ___________ of a lot of different genes at one time. starts with _______, converts to cDNA, then can be used to query differences for genes at the same time. how it works: DNA is _______, adapted and PCR amplified. DNA gets fragmented into _____ base pairs. DNA is labeled at the ends with _______ and is placed into an array. can hold _____ peoples DNA.

hybridization, gene chip, expression, RNA, digested, 25 biotin, 96

primer extension: primers are ______ just upstream of the nucleotide of interest (location of mutation). DNA _______ incorporates complementary bases. this is considered a ______ sequencing reaction. how it works: you design a primer that ends right at the suspected location of ___________. then if the primer matches the DNA, the strands will ________, and extension will occur. if there is no match to primer, there is no extension and that how you know theres a mutation.

hybridized, polymerase, mini, mutation, anneal

DNA alterations and epigenetic changes can work together to lead to cancer. __________ can silence one copy of a _______ and then a mutation can knock out the other copy, resulting in the total loss of function of TSG. ______ epigenetic modifications can also contribute to tumor promoting environments.

hypermethylation, TSG, altered

8. reprogramming metabolism cancer cells have high energy demands because they are growing so fast in a ____________ environment, meaning low oxygen, waste accumulating. cancer cells reprogram the energy pathways to facilitate synthesis of new _______ and amino acids necessary for cell reproduction.

hypoxic, organelles

Newborn screening tests: purpose is to ________ infants at high risk of developing certain inheritable diseases. these conditions are _________, because the treatments and services can be provided to increase the quality of life. panel of about 53 tests for mendelian disorders. blood is taken from babies by __________ and then analyzed for biochemicals, or products of genes that may be _______ in important metabolic pathways and DNA (indirect). all newborns are screened if born in united states hospital. _________ errors of metabolism: involve an enzyme that is missing from a metabolic pathway.

identify, actionable, heelstick, missing, inborn

setbacks to successful gene therapy: viral vectors can trigger the _________ system. can also integrate into __________ and activate proto-oncogenes. gene therapy is getting safer. there are new _______ methods and ______ viral vectors.

immune, chromosomes, delivery, safer

10. tumor promoting inflammation _________ cells infiltrate tumor and result in __________. inflammatory response enhances cancer development and promote tumor growth. immune cells can release growth factors, anti-apoptotic signals and signals to increase blood supply. inflammatory cells also release ROS, ___________ ___________ species that are ___________ and can cause mutations in nearby cancer cells and enable them to become more aggressive.

immune, inflammation, reactive oxygen, mutagenic

_________ types of cancer are usually due to inheriting one defective copy of a TSG. the mutations in TSGs like RB are _____ because it takes two copies to knock out function. however, the _______ ______ acts like a dominant trait. if you inherit one recessive allele of TSG, then you are very likely to acquire the second mutation and have a very high risk of developing cancer. the two hit model is an inherited ________ to cancer. this model applies to _____ inherited forms of cancer. the more common cancer is ________ and requires more than 2 hits.

inherited, recessive, cancer risk, predisposition, rare, multifactorial

6. invading tissues and metastasizing cancer cells can overcome ___________ _______ and invade other tissues and ______ to distant sites in the body. this process is called ___________. it requires the expression of many genes involved in overcoming ______________ signals. normal cells grown on a plate form a monolayer, cancer cells grown on a plate form a __________ and continue growing all on top of each other. metastasis is a multistep process. cancer cells must activate the expression of many genes to drill through the ___________ layer of tissue, enter and exit the ________ stream, and then reinvade at a distant site. few cancer cells survive this process. metastasis is ________ migration. metastatic sites also depend on the _______ of the cancer cells and the new tissue sites.

inhibitory signals, migrate, metastasis, confinement, multilayer, basement, blood, nonrandom, interaction

__________ is a chromosome chart. it is a standard clinical tool for observing chromosomal abnormalities. chromosomes are lined up by ______. physical landmarks are denoted by ___________ patterns that appear when stained during metaphase of mitosis. chromosomes are numbered from ________ to ________.

karyotype, size, banding, largest, smallest

these techniques detect ______ scale deletions, insertions, translocations or entire chromosome duplications. chromosomal alterations of this size are very ______ and usually result in ________ phenotypic effects. _______ _______ _______: bigger than point mutations, but too small to be detected by karyotypes. bigger than 1000 nucleotides in size, so medium sized.

large, rare, significant, copy number variants

ELSI issues with DTC services: liability issues: law has not has time to catch up to DTC, there is little _______ regulation. DTC services say their product helps gain insight into medical information but also attach a disclaimer saying the results are not _________. this is misleading and confusing. education: there needs to be better understanding of risk and _________. medical professionals are very far behind on the genomic revolution and cannot interpret __________ results. will they ever catch up? privacy: who owns the data? how is that controlled? lawmakers argue that keeping genetic information ___________ will stall genomic research and understanding. incidental findings: American college of medical genetics and genomics made a policy that said patients should be alerted to the possibility of ___________ findings. list of conditions, genes and variants should be _________ to patients and health care providers. insurance: if an insurance company has a no pre-existing condition clause, will people be denied __________? does an elevated risk count as a pre-existing condition?

legal, diagnostic, uncertainty, genetic, private, incidental, coverage

_____________: analysis of a collective group of organisms from an environmental sample. isolate DNA, mRNA and proteins from the environmental sample and then you can do genomics, transcriptomics, proteomics for a metagenomic analysis. if you want to know which organisms are there, ______ sequence analysis is most appropriate. this analyzes just the _______ in the environmental sample. provides a sense of __________, species abundant and community.

metagenomics, 16s, rRNA, biodiversity

the collection of microbes that live in association with humans is called the _____________. microorganisms are thought to play a role in a variety of human ______ problems: obesity, heart disease, diabetes, parkinson's. metagenomic tools are being applied to these problems. in our own bodies, microorganisms outnumber human cells in a ratio of _______. these communities are __________, nasal communities are different than GI communities. researchers are sequencing the entire microbiome in different regions to identify all members of the community and figure out their ______.

microbiome, health, 9:1, distinct, role

gene therapy: gene supplementation. used when cell has healthy copy of a gene, it just needs ________ of it. increases gene __________. mostly used in bone ___________. ________, meaning only one allele is lost. gene therapy: cancer therapy the challenge with this therapy is to target _______ cells but protect healthy cells. there is a magic bullet approach being used which targets actively __________ cells with vector based delivery and then treating the entire body with an ______________. another method is _______ T Cell therapy. gene based therapy: using gene to produce a _________ agent but the gene itself is not changed. classic example: _________ DNA technology to produce human ____________.

more, dosage, synthesis, hemizygous, cancer, dividing, antiviral, CAR, therapeutic, recombinant, proteins

the 4 main causes of cancer ultimately lead to ________ in genes. the genes affected are the genes that _________ entry and exit of the _______ ________ or DNA _______. when these genes are mutated, cancer is _______ ________ to occur.

mutation, coordinate, cell cycle, repair, more likely

_______: disorganized tissue growth net _______ in the number of dividing cells a proliferating mass of abnormal cells is a ___________ or a tumor TUMORS LOSE THE BALANCE BETWEEN CELL ___________ AND CELL _________

neoplasia, increase, neoplasm, proliferation, differentiation

detecting CNV's with ______ ________ sequencing technology. this is another way to detect CNVs. how it works: human ______ genome and a ______ genome is cut up to be 3,000 bp long. sequence the ______ of the fragment and map it back to the _______ sequence. if there are no CNVs (which is what should happen) the ends would be 3,000 bases apart. if there is a CNV, the fragments would be ________ bases apart

next generation, reference, sample, ends, reference, 6,000

three main classes of cancer genes: 1. __________ 2. ______ _________ ______ 3. ______ ________ (or genomic stability) genes. ________ and _______ _______ ______ coordinate entry and exit of the cell cycle.

oncogenes, tumor supressor genes, DNA repair, oncogenes, tumor suppressor genes

___________ is the science of how genetic variations affect a body's response to drugs. genes play a role in many aspects and stages of receiving medication: ______ transporters, drug targets, __________, clearance of ______. pharmacogenetics can lead to selecting the best, most ______ drugs for individual patients. genetic testing (SNPs) patients for: 1) _________ chance of suffering an adverse reaction to a drug, 2) _________ a drug that is most likely to be effective, 3) ________ response to drug treatment, 4) _______ the course of illness (prognosis) example: warfarin dosage must be very _______ and the levels need to be carefully monitored. too much warfarin will less to bleeding and too little will lead to clotting. Vitamin K counteracts warfarin so patient _______ must be considered also.

pharmacogenetics, drug, metabolizers, drugs, appropriate, increase, selecting, monitoring, predicting, precise, diet

16s rRNA analysis is a common way to build _____________ trees. using a high throughput technology to build a large scaled phylogenetic tree is called ___________. process of metagenomics: 1. isolate _______ from environmental sample. 2. _________ as much DNA as possible 3. assemble the _______. 4. _______ the data, estimate gene function 5. determine ____________ groups represented.

phylogenetic, phylogenomics, DNA, sequence, data, annotate, phylogenetic

chorionic villi sampling (CVS): cells are sampled from chorionic villi, fingerlike projections into the __________. occurs between 10-12th week of pregnancy. karyotype is prepare directly from cells. procedure has risks 1/1000-3000 procedures results in lethality or birth defects. it cannot detect other genetic disorders, only ________. advantage: can be done _______ and ______ than amniocentesis. disadvantage: less accurate, less safe, less power of ________.

placenta, trisomy, earlier, faster, detection

two hit model of tumor formation: a "hit" is a _____ mutation or a deletion that takes out the function of the good allele. if a baby is born with an inherited hit in their RB gene, they are ________ there to developing cancer. when there is a second hit, it results in no functional copy of the gene, making it actively _______ and cause cancer. the process of the hit: mechanisms in loss of ______________. there are 4 ways to get two hits. 1. _________, 2.________, 3. rescue of ______, 4. mitotic _________.

point, halfway, divide, heterozygosity, mutation, duplication, trisomy, recombination

____________: having an extra set of chromosomes. __________: individual whose cells have _____ sets of chromosomes, causing ploidy to be ___N. this arises from ________ of one oocyte by ______ sperms or when a sperm fertilizes a diploid oocyte. always _______. certain human somatic cells maybe polyploid, such as some ______ cells.

polyploidy, triploid, three, 3, fertilization, 2, lethal, liver

gene therapy: genome editing more _________, fixes problem at the source without using viral vectors. goes right to the source, ______ and causes double stranded breaks and fixes mutations directly. there are no __________ issues. but it is not perfect because it can have severe _______ effects like point mutations, deletions and rearrangements. has potential.

precise, DNA, integration, side

____________ medicine: advanced and customized prevention, characterization of disease and treatment that take individual variability into account. primarily based on individual _______ information. requires many ________ to be analyzed first and requires healthcare professionals to be well __________.

precision, genetic, genomes, educated

BRCA 1 and 2: 10% of all breast cancers can be traced to hereditary _________: inherited mutations in either _______ or ________. if you inherit one copy of mutated BRCA, you are more _______ to develop breast cancer. not a two hit model of cancer, because it requires more hits to cause the cancer. BRCA genes are not tumor suppressing genes, but they are involved in _______ __________. mutations in BRCA causes additional mutations in other _________.

predisposition, BRCA1, BRCA2, likely, DNA repair, genes

Detecting Chromosomal Abnormalities: mostly done for ________ screening. ________ methods: usually done first because quicker, cheaper and less invasive. - can measure levels of ___________ in blood that are correlated with a particular chromosomal composition. - ______________, this cannot detect chromosomes but can detect ________ abnormalities. direct methods: can detect ________ chromosomes. - DNA stains and probes: distinguish a specific chromosome by sequence or _________ pattern. examples include: ______________, chorionic villi sampling (CVS), cell free ______ __________. - any cell except mature ______ can be used to examine chromosomes.

prenatal, indirect, biochemicals, ultrasound, physical, specific, banding, amniocentesis, DNA sampling, RBCs

broadly speaking, cancer has 2 key abilities: 1. ability of cells to ___________ _________ 2. ability to _______ and to ________ to other tissues

proliferate uncontrollably, invade, spread

_____________ normally trigger cell division. when ___________, they become oncogenes. oncogenes are cancer causing genes that act as __________ or ________. these genes produce proteins that have ______ __________ ____________ roles. there are 4 different ways to become activated. 1. ________ or ___________, gene moved to a new locus and is under new controls. 2. gene __________, multiple copies of the gene. 3. ________ mutation within a ______ element. 4. ________ mutation within the _______. alterations to proto-oncogenes are usually ______ and lead to a ______ of ________ mutation, where it keeps __________ all the time.

proto-oncogenes, activated, drivers, initiators, signal transduction pathway, translocation, transposition, amplification, point, control, point, gene, dominant, gain function, signaling

pathogen detection: uses _____ or real time PCR. this is faster and more _______ than normal PCR plus it provides more __________ than regular PCR. how it works: starts with ______ extracted from blood sample. detect the pathogens _______ ______. qPCR is more sensitive because it can cut out irrelevant nucleic acids of other things and just focus on pathogen nucleic acid. also used the quencher/reporter setup. the ________ assay is the first qPCR invented. steps for Taqman: 1. unbound ______ is free in solution. 2. probe and primer bind to target DNA, _______ occurs. 3. Taq polymerase extends and _________ probe. donor dye emits glow, signaling accumulation.

qPCR, precise, information, DNA, nucleic acid, taqman, probe, FRET, hydrolyzes,

9. promoting genomic instability there are 3 main paths to genomic instability: ___________ mistakes, mistakes made during _________, defective DNA __________. cancer is a ___________ trait, many gene alterations need to occur. gene alterations are accumulated in a stepwise manner to result in cancer. it is estimated that alterations _____ to ____ genes is necessary in the establishment of cancer. the __________ model of cancer is prominent theory in cancer biology. many steps are required for a cell to acquire the hallmarks of cancer, each step is a result of a genetic alteration.

replication, mitosis, repair, multifactorial, 3, 7, multistage

1. evading growth suppressors pRB stands for ________________ protein and is key in cancer development. it is a tumor suppressor protein that ______ progression through the cell cycle. mutations in Rb prevents RB protein from inhibiting the growth cycle, meaning a mutant RB causes _____ of _________. it takes two mutant RBs to knock out its function, making it ______ mutation. retinoblastoma is a rare childhood cancer of the _____ that occurs in hereditary and spontaneous forms. in RB patients, it is noticed that they are missing part of chromosome ____. the _____ ______ model is needed to deactivate the RB gene.

retinoblastoma, inhibits, loss, function, recessive, eye, 13, two hit

two types of translation: ______________ translocation: two _____ arms of nonhomologus chromosomes break off and then the long arms combine into one large translocated chromosome. the remaining short arms are ______. this is ________. ___________ translocation: two __________ chromosomes exchange parts. a translocation can produce __________ gametes, which results in a zygote with net gains or losses in genes.

robertsonian, short, lost, rare, reciprocal, different, unbalanced

advantages of pharmacogenetics: better, ______ drugs from the start ____________ drug dosages more accurate and powerful _______ __________ screening of disease fewer side ________ improved ___________ improvements in drug _________ decrease in overall ____ of healthcare ____________ is a great resource for pharmacogenetic information

safer, appropriate, medicine, advanced, effects, vaccines, discovery, cost, pharmGkb

indirect methods are used for ____________. screening with multiple _________ serum markers indicates individuals with an increased risk of a fetus abnormal chromosome numbers. panel of maternal serum markers + _________ findings + maternal ______ = 90% probability of detecting __________. however this is not ____________. if the screening indicates an elevated risk of trisomy, then direct and diagnostic testing is the next step, which _________ the chromosomes. maternal serum markers are offered to all pregnant women because they are safe and inexpensive. results are returned as a MOM values, _____ of the _______. this indicates how far an individuals results _____ from the normal range. a MOM of 2 means the value is _______ as high or low as the average in normal pregnancy.

screening, maternal, ultrasound, age, trisomies, diagnostic, visualizes, multiple, median, deviates, twice

precision medicine initiative: why now? time is right because of __________ of the human genome, improved __________ for biomedical analysis, and new ______ for using large data sets. near term goals: to cure cancer using _________ trials of targeted drugs, ________ therapies and knowledge to overcome drug __________. long term goals: _________ pharmacogenetics, the right drug for the right patient at the right dose, identify new targets for treatment and prevention, test whether _________ ________ can encourage healthy behaviors, and lay the scientific foundation for precision medicine for many _______. advanced, high throughput sequencing technology made whole genome sequencing _________ and feasible.

sequencing, technology, tools, clinical, combination, resistance, advance, mobile devices, diseases, affordable

immunotherapy is an up n coming cancer treatment that 1) boost the immune system to work harder or ______ to attack cancer cells, 2) provide man-made immune system _________. there are 3 types of immunotherapy: ____________ inhibitors, cancer ___________, ________ cell therapy. cancer cells inhibit suppress T cells and inhibit checkpoints. immunotherapy allows T cells to stay _________. T cells recognize other cells using receptors and can't recognize cancer cells, but ____ cells can. however, they can't kill cancer cells. so chimeric ________ receptor T cell therapy combine the recognition ability of B cells with the killing ability of T cells to created a cancer killing machine. best thing about CAR T cell therapy is that the T cells are _________ from the patient themselves and are made very specifically. `

smarter, components, checkpoint, vaccines, CART, active, B, antigen, isolated

somatic gene therapy is a common type of gene therapy. addresses only __________ cells and is ______ passed down to next generation. challenges of gene therapy: 1. __________ healthy genes to appropriate cells 2. control ________ of wild type gene to be therapeutic. 3. avoid ________ other cells. 4. avoid triggering _________ response.

somatic, not, delivering, dosage, harming, immune

PCR-RFLP or Snip-SNP is a ___________, older technique. up to 1/2 of all SNPs occurs within a ________ enzyme site. how it works: you PCR amplify the region of DNA containing the SNP and cut with restriction enzyme. then you visualize the products by gel _________. if SNP is present then the DNA restriction site is destroyed, causing different ________ patterns than normal. this is the same process used in DNA ____________. SNPs are used a genetic _________.

straightforward, restriction, electrophoresis, banding, fingerprinting, markers

7. Escaping Immune Destruction cancer cells do not display normal cell proteins on their _________. the immune system is constantly monitoring the body for irregular cells and cancer cells escape detection by the immune system to survive. how? cancer cells don't display ______ molecules, they ________ surface molecules and _______ immune cells. they also surround themselves with a dense layer of _____ for protection and sometimes divide so quickly that immune system can't keep up.

surface, surface, swallow, suppress, tissue,

general classes of cancer treatments: __________: suitable for benign tumors, self contained. _________: metastatic tumors, leukemias and lymphomas. _________: used for solid, malignant tumors. these are the big 3 that can be used together. _________ and ________ have toxic side effects because they target _________ dividing (________) cells. precision medicine approaches that are becoming more prominent: _________ therapy, _____________, oncogene specific _______. precision medicine is trying to target just ________ cells, protect the healthy cells.

surgery, chemotherapy, radiation, chemotherapy, radiation, actively, healthy, hormone, immunotherapy, inhibitors, cancer

5. becoming immortal to grow indefinitely, cancer cells must maintain their __________. these are the repeated ends that protect chromosomes from fusing together. as cells age, the telomeres ________. ________ is an enzyme that is activated in cancer cells which lengthens the telomeres and prevents the ends of chromosomes from erosion. telomere is the _____, non coding stained region. cancer cells express a lot of genes that are normally only expressed during ________. Dr elizabeth blackburn won nobel prize in medicine for discovery of telomerase and telomeres. __________ telomeres is a significant area of research to treat cancer. thought to be a magic bullet.

telomeres, shorten, telomerase, dark, embryogenesis, inactivating

translocation: when the ____ of chromosomes break off and _____ ends. outcome is that some of the chromosome is _____ and cell _____ occurs. the philadelphia chromosome promotes cell ________. Phil chromosome is made when the tips of chromosome ____ and ____ break off and switch ends with each other. the ____ gene from chromosome 9 attaches to chromosome 22's ______ promoter. bcr is always _______, therefore causing cell division. this type of translocation is commonly found in _____ and __________.

tips, switch, lost, death, division, 9, 22, all, bcr, signaling, leukemias, lymphocytes

10 hallmarks of cancer: 1. _________ growth 2. evading _________ suppressors 3. evading cell __________ 4. obtaining ________ 5. becoming ________ 6. ________ tissues 7. escaping immune ________ 8. reprogramming _______ 9. promoting genomic ___________ 10. tumor promoting ____________

uncontrollable, growth, death, nutrients, immortal, invading, destruction, metabolism, instability, inflammation

two general strategies for somatic gene therapy: in _______: direct delivery ___ ______: cell based delivery (using vectors) where does healthy gene come from? generated through ______ DNA technology. soon healthy genes will be made synthetically. how to get the DNA into the cells? physical and chemical methods are possible. most gene therapies use __________.

vivo, ex vivo, recombinant, vectors.

3 major types of genome editing: 1. _____ finger nuclease (ZFN) technology 2. transcription-___________-like effector nuclease (TALEN) technology 3. clustered regularly __________ short palindromic repeats (CRISPRs) ZFN and TALEN were first but they are _____, less control and expensive. they cut only _____ gene at a time and are _______ based. CRISPR uses ____, is cheaper, and can remove, replace, add more than one gene at a time so its very __________. all can be done in _______ or germline cells.

zinc, activator, interspaced, slow, one, protein, RNA, versatile, somatic