Term
| 3 general types of genetic disease etiologies |
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Definition
1) chromosomal aberrations (abnormal chromosome structures or numbers of chromosomes)
2) inherited disease involving one gene
3) multifactorial genetic diseases |
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Term
| 2 approaches used to study chromosomal aberrations |
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Definition
| karyotyping (selective staining) and fluoresecent in situ hybridiziation (FISH) |
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Term
| 3 approaches used to study inherited diseases involving one gene |
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Definition
| pedigree to identify inheritance and affected individual, sequencing of genes, family specific mutation (genetic test using the polymerase chain reaction and a specific probe). |
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Term
| 1 approach used to study multifactorial genetic diseases? |
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Definition
| associated single nucleotide polymorphisms identified using DNA microarrays |
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Term
| karyotypes fall into what type of study? |
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Definition
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Term
| what do you look to identify in terms of chromosomal aberrations when you karyotype (selectively stain)? |
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Definition
| identify variations in structure and # of chromosomes |
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Term
| what does an idiogram reveal in terms of chromosomal aberrations, once you've identified the variations in structure/# of chromosomes? |
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Definition
| there is a normal banding pattern in chromosomes. change in band width or missing bands means there is a chromosomal abnormality. |
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Term
| what part of the chromosome does FISH focus on? |
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Definition
| the ends of the chromosome (telomeres) because there are repeated bases on the end. every time the chromosome divides, the telomere gets a little shorter. so we associate telomeres with aging process. ends of chromosome tend to be sticky, so it is possible for end to break off. to focus on tip of chromosome and ascertain whether telomere region is intact or not, we need to use FISH method. the fish method uses telomere specific probes to check for structural changes. |
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Term
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Definition
| we know the base sequences of the telomere region. so we artificially produce florescent probes with complementary oligonucleotide bases to telomere region. |
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Term
| how long are the oligonucleotide probes that we use for FISH? |
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Definition
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Term
| how are the oligonucleotide probes used for FISH labeled? |
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Definition
| with a radioactive tracer, histochemical compound or florescent dye. |
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Term
| describe the length/sequence of a telomere |
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Definition
| In general, telomeres consist of a 6-8 base-pair sequence that is repeated hundreds or thousands of times. Human telomeres range in size from 2-50 kilobases and consist of approximately 300-8,000 precise repeats of the sequence CCCTAA/TTAGGG. |
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Term
| what is characteristic of almost all eukaryotic telomeres? |
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Definition
| tandem repeats of short GT-rich sequences |
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Term
| once you've stuck the oligonucleotide probe onto the telomere and labeled it in the FISH method, what happens to the DNA? |
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Definition
| it denatures and hybridizes via pH change so that the probe's complementary bases can match up with the chromosome's base pairs. |
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Term
| what is spectral karyotyping (chromosome painting)? |
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Definition
| different probes of different colors from the fish method are used to represent different chromosomes. there may be different labeled fluorescent colors on a given chromosome. |
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Term
| describe pedigree analysis as a method of studying single gene disorders |
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Definition
| first way you know there is abnormality in family is by doing family history and looking at affected individuals. this analysis helps us to determine inheritance pattern of diseases. |
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Term
| method of identifying candidate gene in single gene disorder |
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Definition
| you can't look through the 3 million base pairs to find the gene, so you have a good idea of the protein that's abnormal in the gene. ex: in sickle cell anemia, hemoglobin protein gene is the problem. so you look at those genes and see which has the abnormality. identify the affected protein and do reverse from protein to RNA to DNA to gene. in sickle cell, this leads you to find that the beta globin gene is the the problem in that single gene disorder. |
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Term
| how do you synthesize appropriate probe for single gene disorder? |
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Definition
| test on person's dna amplified by polymerase chain reaction. |
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Term
| describe price in genome sequencing |
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Definition
| it is falling. exome sequencing about $900 in 2013. |
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Term
| in testing for sickle cell, what kinds of probes will you construct? |
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Definition
| 1 probe to identify normal beta-globin gene, and 1 to identify sickle cell base sequence gene. individual may have both genes. |
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Term
| if probes reveal that individual has genes for both normal beta globin genes and sickle cell anemia, what will the heterogenous zygote's phenotypical presentation be? |
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Definition
| sickle cell is autosomal recessive, so the individual won't have this disorder. |
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Term
| how do you make copies of a small segment of dna? |
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Definition
| polymerase chain reaction |
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Term
| how is the polymerase chain reaction useful (why would we want to detect amplify and probe a small segment of DNA)? |
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Definition
| with just a small sample from mom and dad, you can detect a hereditary disease. this is helpful in prenatal diagnosis in a family that is concerned about certain genetic inheritance patterns. |
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Term
| specificity of genetic testing lies in specificity of ___ |
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Definition
| probe that's going to be synthesized to be complementary. So for this utilization of PCR to to work and enable you to detect a hereditary disease/family-specific mutation, you have to know the specific mutation in a particular family for a particular disease. |
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Term
| how many cystic fibrosis causing mutation are there in the cystic fibrosis transmembrane conductance regulator gene? |
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Definition
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Term
| there is currently a genetic test that screens for __ of the most common CF mutations.depending on the ethnic background, this test can detect 30-90% of all CF carriers. |
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Definition
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Term
| in testing for CF, what does a positive result mean? |
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Definition
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Term
| in testing for CF, what does a negative result mean? |
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Definition
| it doesn't necessarily mean that the individual is not a carrier. |
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Term
| the genetic test for cf is most accurate for what demographics? |
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Definition
| caucasians and ashkenazi jews since it detects the mutations most commonly found in these populations. |
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Term
| 1 in __ caucausians carry one mutant cystic fibrosis gene. about 1 in __ caucasian babies will be born with CF. |
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Definition
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Term
| what early/aggressive interventions can help a baby born with CF? |
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Definition
| antibiotics, pancreatic enzyme therapy, physical therapy. |
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Term
| what is the location of the most common mutation for CF? |
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Definition
| position 508 of the protein. involves the deletion of a phenylalanine amino acid due to the deletion of 3 bases. |
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Term
| why is testing for CF complicated? |
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Definition
| it's a large gene with the potential for mutation. different groups of people have different mutations and if you're not caucasian or jewish, it's harder to find the mutation. a negative test could happen in someone with a CF mutation because the test only tests for the 70 most common mutations. you need to sequence the entire gene to identify the specific mutation in the family if it's not on the most 70, and that is time consuming and $$. |
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Term
| best known mutations associated with breast cancer |
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Definition
| BRCA 1 and 2 (think angelina jolie) |
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Term
| what is the role of BRCA genes? |
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Definition
| tumor suppressors primarily. also repair homologous dna, promote genomic stablity, transcriptional regulation, protein ubiquitination, chromatin remodeling, cycle cycle control. |
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Term
| inherited mutations in BRCA genes show ___ __ inheritance and increase the lifetime risk of cancer by ___% |
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Definition
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Term
| what is the most common genetic variation in people? |
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Definition
| single nucleotide polymorphisms (SNPs) ("SNIPS") |
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Term
| what does each snp represent? |
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Definition
| difference in a single dna building block called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. |
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Term
| SNPs occur normally throughout a person's ___ |
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Definition
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Term
| They occur once in every ___ nucleotides on average, which means there are roughly 10 million SNPs in the human genome. most commonly, these variations are found in the dna between __. |
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Definition
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Term
| how are SNPs helpful to scientists |
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Definition
| they act as biological markers and help them locate genes that are associated with disease. |
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Term
| when do SNPs play a more direct role in affecting the gene's function? |
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Definition
| when they occur within a gene or in a regulatory region near a gene. |
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Term
| Do SNPs usually have an effect on health or development? how are they helpful in predicting health issues? |
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Definition
| no. but some of these genetic differences prove to be important in the study of human health, because researchers have found SNPs that may help predict an individual's response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases. SNPs can also be used to track the inheritance of disease genes within families. |
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Term
| what kind of technology is used to identify an SNP associated with an increased risks of a multifactorial disorder? |
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Definition
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Term
| what company used iceland to identify risk genes?why was iceland a good choice? |
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Definition
| Decode Me. relatively isolated population without much immigration. country has excellent medical recording system. |
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Term
| what 2 things are involved in multifactorial diseases? |
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Definition
| genetic factors (one or more) and environmental factors |
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Term
| what is the largest category of diseases in terms of patient number? |
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Definition
| multifactorial diseases (ex diabetes, cvd, some cancers, arthritis, immunological disorders, some mental illnesses) |
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Term
| what percent of bases do you have in common with your neighbor? |
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Definition
| 99% (that 0.1% variability occurs every 300-1000 bases) |
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Term
| how do you figure out which snips are associated with multifactorial diseases |
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Definition
| compare between affected and unaffected individuals' genomes. |
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Term
| how a genome-wide association study works in terms of height comparison |
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Definition
| look at consistent specific genomic differences in people who are tall vs. people who are short. |
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Term
| what is microarray technology used for? |
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Definition
| identifies common polymorphisms, amplifies the dna and uses fluorescent label. |
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Term
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Definition
| contains many cells with specific sequences of bases attached to grid. the locations in the genome are common polymorphism locations. you can buy an SNP chip with one million SNPs. the last base varies (eg T instead of A) |
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Term
| how does microarray technology REALLY work? (a few steps?) |
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Definition
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Term
| uses for microarray technology / DNA snp chips? |
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Definition
| your snip profile can be used to identify disorders for which you have an increased risk by identifying your profile to large database of people. it compares your snps with common multifactorial diseases like certain mental health diseases or cvd. usually risk is quite small. |
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Term
| fda banned the company that sold genome wide association tests (GWAS) because __ |
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Definition
| there isn't sufficient research supporting their reported results of risk of having a particular disease. for example, the company 23andme reported risks based on one individual. |
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Term
| snps can be helpful in predicting severity of __. example: |
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Definition
| symptoms (different genetic snps --> different symptoms.) example: chromosome 11 snp associated with milder symptoms and chromosome 21 snp had more severe symptoms (incidentally this gene is near to genes that function in the lungs). |
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Term
| how are snps helpful in predicting drug response and managing drug therapy? |
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Definition
| snp can predict pharmacogenomics and see if the patient is a responder, non responder, or toxic responder to drugs. responders should be treated with conventional drug dose, and non/toxic responders should be treated with an alternative drug or dose. |
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Term
| Pharmacogenomics can play an important role in identifying ____, ___, __. |
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Definition
1) identifying responders and non responders to medications
2) avoiding adverse events
3) optimizing drug dose |
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Term
| 5 examples of drugs with pharmacogenomic labeling? |
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Definition
1) Warfarin - cardiac and hematology - clotting
2) Metformin - diabetes - glucose control
3) Omeprazole - GI -proton pump inhibitor
4) Tamoxifen - oncology
5) Diazepan - psychiatry |
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Term
| what are 3 applications of microarray technology that don't have to do with looking at snps, but rather have to do with gene expression in tissues and what messenger RNAs and proteins are made? |
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Definition
1) tumor classification - gene expression
2) disease prognosis - gene expression
3) therapy guidance - gene expression |
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Term
| what is dna microarray tumor typing technology? how does it work? |
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Definition
| you compare tumors by looking at normal tissue and tumor tissue, comparing messenger rna/proteins of both tissues. you made cdna via reverse transcription, labeling nucleotides and making complementary dna. if tissue is normal, it will be green. if tissue is tumorous, it will be red. if a combo, it will be yellow. hybridize probe to microarray and scan. |
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Term
| polymerase chain reactions are used in what crimical evidence science? why? |
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Definition
| forensics for dna profiling. |
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Term
| how are biotechnologies used in drug production? |
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Definition
production of recombinant proteins --> safer and cheaper drugs! examples of such drugs:
A. Insulin ( Humulin) - treatment for Type I diabetes
B. Factor VIII - treatment for Hemophilia A
C. Streptokinase - treatment for blood clots
D. Interferon - has antiviral and anticarcinogenic acitivites. also used to treat some autoimmune diseases. |
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Term
| gene therapy application of biotechnologies in health care does what? |
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Definition
| entails the ability to replace defective or missing genes. this is still progressing and is very complicated. |
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Term
| use of PCR products in microbiology? |
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Definition
| detecting bacterial and viral infections. |
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Term
| Basic process for production of recombinant dna proteins?example of positive effect |
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Definition
| isolate the dna of interest. insert dna into plasma wiht same restriction enzyme that cleaves dna. dna ligase seals human gene and plasmid. host cell takes up recombined plasmid. gene cloning occurs. effect could be production of insulin to treat type 1 dm. |
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Term
| 4 steps of adoptive cell transfer gene therapy |
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Definition
1) t cell collection
2) t cell transfection
3) t cell adoptive transfer
4) patient monitoring |
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Term
| summary of uses of biotechnologies (7) |
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Definition
1.Identify chromosmal abnormalities
2.Determine mutations in genes
3. Identify SNPs associated with increased risk of disease, severity of disease symptoms and drug outcomes
4. Clone ( amplify) DNA using the polymerase chain reaction ( PCR)
5. Type tumors and select treatments by looking at gene expression
6. Produce recombinant proteins
7. replace defective genes - a work in progress |
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