Term
| describe the numbers of the human genome sequence |
|
Definition
| 3 billion base pairs, 20000-25000 genes due to alternative splicing |
|
|
Term
| currently, what is the human genome sequence used for |
|
Definition
|
|
Term
| what are the main achievements currently in bio technology |
|
Definition
| restriction endonucleases, DNA sequence, cloning DNA, creation of synthetic probes, PCR |
|
|
Term
| what is another name for a restriction enzyme |
|
Definition
|
|
Term
| what does a restriction enzyme do |
|
Definition
| cleave specific DNA sequences |
|
|
Term
|
Definition
| a 4-8 base pair sequence that reads the same 5'-3' on both strands and is cleaved by an endonuclease |
|
|
Term
| what is the result after a restriction enzyme does his job |
|
Definition
|
|
Term
|
Definition
| overlaping sequence made by a restriction enzyme (zipper like) |
|
|
Term
|
Definition
| direct cut of a DNA sequence by a restriction enzyme (not zipper like) |
|
|
Term
| after a restriction enzyme cleaves, how is it possible that the area can be ligased if it was ruiened |
|
Definition
| 3' OH and 5' phosphate are attached after clevage |
|
|
Term
| what is a restriction site |
|
Definition
| the sequence a restriction enzyme is cleaved, the palendrome |
|
|
Term
| describe the relationship between the recognition sequence length and the frequency of DNA cuts |
|
Definition
| the shorted the restriction site the more frequent it will be |
|
|
Term
|
Definition
| a compliation of cleaved restriction sites that have been ligated |
|
|
Term
| what type of restriction site cleavage is easier to work with |
|
Definition
|
|
Term
| describe the basic concept of DNA cloning |
|
Definition
| a restriction sequence is inserted into a cloning vector in host cells, DNA is cloned by the cell and amplified making recombinent DNA |
|
|
Term
|
Definition
| a DNA molecile that accepts foriegn DNA fragments |
|
|
Term
|
Definition
|
|
Term
| what are the requirements of a vector for it to work with DNA cloning |
|
Definition
| autonomous replicationin the cell (so it needs an replication origin sequence), at least one restriction site, at least 1 gene for selection |
|
|
Term
| describe what a selection gene is and why it is needed |
|
Definition
| it ia gene within a vector that codes for some sort of selection, like an antibiotic resistance, because not all cells will have a vector with the restriction sequence in it and you need to weed out the ones that dont |
|
|
Term
| what are the common host cells for vectors |
|
Definition
| bacteria, yeast artificial chromosomes, retroviruses, yeast, phages |
|
|
Term
|
Definition
| a virus that infects bacteria |
|
|
Term
| what is a mammalian virus |
|
Definition
|
|
Term
| what are the types of DNA libraries |
|
Definition
|
|
Term
| what is the process of creating a genomic DNA library |
|
Definition
| take DNA from an organism, chop it up with restriction enzymes, ligate to a vector, let the host make many copies of each gene piece |
|
|
Term
| what does a genomic DNA library contain in the end |
|
Definition
| all sequences in the genome: introns, exons, promoters, etc |
|
|
Term
| what is the basic definition of a cDNA library |
|
Definition
| DNA compliment of mRNA that gives a snap shot of what was going on in that cell at that time |
|
|
Term
| describe the process of making a cDNA library |
|
Definition
| get a particular mRNA sequence from a cell, use reverse transcriptase to get a single DNA strand, use DNA polymerase to make it a double strand, put DNA into a vector and allow it to replicate |
|
|
Term
| in the end what does a cDNA library contain |
|
Definition
| no promoters, no introns, only mRNA |
|
|
Term
| how can a cDNA library be used after it has been made |
|
Definition
| put DNA clones into an expression vector to make mRNA then make protein |
|
|
Term
| describe the process of DNA sequencing |
|
Definition
| divide ssDNA, dNTPs, primers, and polymerases into 4 tubes into 4 tubes, add a specific dideoxyribonucleotide to each tube, synthesis proceedes until a dNTP is added in each strand, gel elecrtophoresis divides by length of products |
|
|
Term
| what do you need to do DNA sequencing |
|
Definition
| ssDNA, dNTPs, primer, polymerase |
|
|
Term
| what does DNA sequencing accomplish |
|
Definition
| determines the exact sequence of cloned DNA |
|
|
Term
|
Definition
| to identify DNA fragments |
|
|
Term
|
Definition
| ssDNA labeled (radioactivly usually) that can be hybrixised to ssDNA that is complimentary |
|
|
Term
|
Definition
| when target DNA is made single stranded by a method like heat or chemicals |
|
|
Term
| if probes use ssDNA how do they not reanneal |
|
Definition
| nitrocellulose membrane solid supports |
|
|
Term
| what happens when a nitrocellulose membrane is exposed to a probe |
|
Definition
| if complimentary, probe will bind and can be identified by autotraiography |
|
|
Term
| how long is a small probes |
|
Definition
|
|
Term
| how are small probes made |
|
Definition
| chemically synthesized oligonucleotides the same way synthetic primers are made |
|
|
Term
| what is the purpose of small probes |
|
Definition
| very specific, can identify a single base pair mutation |
|
|
Term
| how are large probes made |
|
Definition
| reverse transcription, PCR, etc. |
|
|
Term
| what is the function of large probes |
|
Definition
| can identify similar genes in different organisms or the same gene in different indiviguals that may not be exactly the same sequence |
|
|
Term
| what does southern blotting analize |
|
Definition
|
|
Term
| describe the process of southern blotting |
|
Definition
| isolate DNA, chop it with restriction enzymes, gel electrophotesis, denature DNA, blott it to immobilize it on the membrane, probe the blot |
|
|
Term
| what does southern blotting focus on |
|
Definition
|
|
Term
| what does northern blotting target |
|
Definition
|
|
Term
| describe the requirements for northern blotting |
|
Definition
| do not need to make a single stranded, probe must be complimentary to the mRNA |
|
|
Term
| what does northern blotting specifically detect |
|
Definition
|
|
Term
|
Definition
| tissue or cell specific studies, measure gene expression |
|
|
Term
| what does a western blot target |
|
Definition
|
|
Term
| what is the probe in a western blot |
|
Definition
| antibody specific to the protein of interest attached to an enzyme |
|
|
Term
| what is the function of a western blot |
|
Definition
| quantative, tells how much protein you have |
|
|
Term
| what is a restriction fragment length polymorphism (RFLP) |
|
Definition
| genetic differences due to polymorphisms in one of the 99.9% noncding regions that are inheriently not harmful or do not containa phenotype |
|
|
Term
| what are the requirements to be considered a RFLP |
|
Definition
| create or deletes a restriction site, has more or less of a type of repeated sequence |
|
|
Term
| what are the causes of RFLP |
|
Definition
| single nucleotide polymorphisms, disease causing mutation, harmless changes, tandem repeats |
|
|
Term
| what can single nucleotide polymorphisms (SNPs) cause |
|
Definition
| create of abolish a restriction site, 90% of the genetic variation in humans |
|
|
Term
| what does a variable number of tandem repeats (VNTR) refer to? |
|
Definition
| human genome contains many regions where a sequence is repeated intandem many times that varies greatly from person to person that are not related and some between people related |
|
|
Term
| physycally, how is a RFLP produced |
|
Definition
| DNA is cleaved on either side of a VNTR |
|
|
Term
|
Definition
| single nucleotide change that makes or abolishes a restriction site messing p the action of the restriction enzyme giving different sized fragments when run on a gel |
|
|
Term
| compared to VNTR describe the prevlience of SNP in the genome |
|
Definition
| SNPs are distributed through out |
|
|
Term
|
Definition
| to locate a diseased gene (not that it is the disease causing mutation but they tend to be near them), to mark allales (disease markers) |
|
|
Term
| what does it mean that a tandem repeat is hypervariable |
|
Definition
| different in all people especially in those not related |
|
|
Term
|
Definition
| not associated with disease, for paternity testing, forensics, molecular finger print |
|
|
Term
| what do you need to know to do a PCR |
|
Definition
| the flanking sequence around the sequence you want to amplify |
|
|
Term
| what are the advantages of PCR |
|
Definition
| amplify small amounts of DNA many times in a few hours, all in one test tube, DNA can be used for many reasons, amplify mutations to learn sequence, detect latent viruses, forensics, safer amniocentesis |
|
|
Term
| describe the process of PCR |
|
Definition
1. design primer to find flanking sequences,
2. denature DNA to make ssDNA using heat close to water boiling point
3. add primer to get DNA polymerase started, cool a bit so primer can anneal
4. chain extension using dNTPs and DNA polymerase
5. repeat steps 2-4 20-30 times |
|
|
Term
| what is a flanking sequence |
|
Definition
| approx 20 base pairs on each DNA strand before the DNA sequence you want to do PCR on so a primer can identify it |
|
|
Term
| in PCR, when you cool after denaturing so the primer can bind, does the DNA strand not just re-anneal |
|
Definition
| because we add lots of primer to make that unlikley and the cooling is very fast |
|
|
Term
| what happens if in PCR the middle part of the DNA strand (between the primers) reanneals during cooling |
|
Definition
| DNA polymerase will push it back open when it comes by |
|
|
Term
|
Definition
| part of its life it is hidden in the genome at low levels, can be found with PCR |
|
|
Term
| how does PCR help forensics |
|
Definition
| small sample size is ok now, just amplify |
|
|
Term
| how did PCR make prenatal genetic testing safer |
|
Definition
| during amniocentesis, smaller sample size is used because we can just amplify, less invasive |
|
|
Term
| how can we assess mRNA levels |
|
Definition
| northern blot, microarray |
|
|
Term
| how are the results of a northern blot interperted |
|
Definition
| band = yes the mRNA was expressed, band width tells quantity |
|
|
Term
| what does a microarray show |
|
Definition
| mRNA expression for 1000s of genes at a time |
|
|
Term
| how does a microarray work |
|
Definition
| glass slide with 1000s of divits, each divit has ssDNA with a compliment to gene with bases pointed outwards, isolate the mRNA sample and make cDNA copy, if compliment is on slide it will bind to it. always comparing 2 samples |
|
|
Term
| how do you read microarray results |
|
Definition
yellow: samples are equal in expression
black: only one sample had expression
red: one sample expressed more
green: the other sample expressed more |
|
|
Term
| what reads the results of a microarray |
|
Definition
| a machine that can analize the exact shades and determine conecntrations |
|
|
Term
| what does proteomics evaluate |
|
Definition
| proteins made in a cell, post translational modifications, turn over of proteins, tissue comparison, enzyeme modulations |
|
|
Term
| what does ELIZA stand for |
|
Definition
| enzyme linked ammunosorbent assay |
|
|
Term
|
Definition
| protein is linked to an enzume and put in a 96 microwell plate, antigen is bound to plate well, probe with antibody is linked to the enzyme, add colored substrate to see how much protein bound, bound protein = protein made in cell |
|
|
Term
| how do you read the results of a western blot |
|
Definition
| gives color reaction and exact band size |
|
|
Term
| what protein / DNA expression techniques use a gel |
|
Definition
| southern, northern, and western blot, proteomics, PCR (maybe) |
|
|
Term
| what protein / DNA expression techniques are quantative |
|
Definition
| norther and western blots, microarray, elisa, proteomics, PCR sometimes |
|
|
Term
| what protein is affected by a sickle cell anemia mutation and how |
|
Definition
| b-globin by eliminating a restriction site |
|
|
Term
| what type of mutation is involved in sickle cell anemia |
|
Definition
| a point mutation creating a RFLP |
|
|
Term
| why is sickle cell anemia a special type of RFLP |
|
Definition
| because it is one of the few times where the RFLP mutation is disease causing |
|
|
Term
| what are the ways you can test for sickle cell anemia |
|
Definition
| PCR, southern blot, allele specific olegonucleotide probes |
|
|
Term
| explain how to interpert the results of a southern blot for sickle cell anemia |
|
Definition
| sickle cell has one larger (higher on gel) band, a carrier has two bands, a normal allele will have one smaller band |
|
|
Term
| what type of inheritence does sickle cell have |
|
Definition
| recessive, a heretozygote will have no symptoms |
|
|
Term
| explain the process of doing a PCR to detect sickle cell anemia |
|
Definition
| design a primer to flank the B-globin gene, amplify the mutation region, digest the fragment with a restriction enzyme and run a gel |
|
|
Term
| where does the specificity come from when running a PCR to determine sickle cell anemia |
|
Definition
| designing a primer for the mutation region |
|
|
Term
| describe how to read the results for a PCR on sicle cell anemia |
|
Definition
| there will be one larger (higher on gel) band for sickle cell and two smaller bands for a normal patient |
|
|
Term
| describe the process of allele specific olegonucleotide probing |
|
Definition
| get samples from people, make two wells per person, probe one well with the normal gene and one with the mutated gene, add in the samples, see which well has the reaction |
|
|
Term
| what types of mutations can allele specific olegonucleotide probing find |
|
Definition
|
|
Term
| what gene is mutated in cystic fibrosis, what does this gene have a role in |
|
Definition
|
|
Term
| what is the most common lethal genetic mutation in caucasions |
|
Definition
|
|
Term
| what are some of the symptoms of cystic fibrosis |
|
Definition
| chloride in sweat, lack of chloride secretion in the lungs leading to infection and mucus build up, build up of mucus in the pancreas, death around age 30 |
|
|
Term
| what type of mutation affects most people with cystic fibrosis, what amino acid is missing due to it |
|
Definition
|
|
Term
| what test do we use to determine cystic fibrosis |
|
Definition
|
|
Term
| what type of inheritence is cystic fibrosis |
|
Definition
| recessive, need two mutant genes to get the symptoms |
|
|
Term
| describe how to do a PCR to test for cystic fibrosis |
|
Definition
| possible deletion area is flanked making different size products depending on if the deletion area is there or not |
|
|
Term
| describe how to interpert the results of a PCR for cystic fibrosis |
|
Definition
| the mutant will have one smaller band (it weights less because of the cut due to the mutation), the normal will have one larger band, a carrier will have both bands |
|
|
Term
| describe the process of allele specific olegonucleotide probing |
|
Definition
| get samples from people, make two wells per person, probe one well with the normal gene and one with the mutated gene, add in the samples, see which well has the reaction |
|
|
Term
| what types of mutations can allele specific olegonucleotide probing find |
|
Definition
|
|
Term
| what gene is mutated in cystic fibrosis, what does this gene have a role in |
|
Definition
|
|
Term
| what is the most common lethal genetic mutation in caucasions |
|
Definition
|
|
Term
| what are some of the symptoms of cystic fibrosis |
|
Definition
| chloride in sweat, lack of chloride secretion in the lungs leading to infection and mucus build up, build up of mucus in the pancreas, death around age 30 |
|
|
Term
| what type of mutation affects most people with cystic fibrosis, what amino acid is missing due to it |
|
Definition
|
|
Term
| what test do we use to determine cystic fibrosis |
|
Definition
|
|
Term
| what type of inheritence is cystic fibrosis |
|
Definition
| recessive, need two mutant genes to get the symptoms |
|
|
Term
| describe how to do a PCR to test for cystic fibrosis |
|
Definition
| possible deletion area is flanked making different size products depending on if the deletion area is there or not |
|
|
Term
| describe how to interpert the results of a PCR for cystic fibrosis |
|
Definition
| the mutant will have one smaller band (it weights less because of the cut due to the mutation), the normal will have one larger band, a carrier will have both bands |
|
|
Term
| what type of inheritence is PKU |
|
Definition
|
|
Term
| why are all newborns screened for PKU |
|
Definition
| because the symptoms can be avoided with a special diet |
|
|
Term
| what process is inhibited during PKU |
|
Definition
| phenylalanine turning into tyrosine |
|
|
Term
| why can we use ASO probing or PCR to find PKU |
|
Definition
| because there are over 400 mutation site possibilities and you would have to make over 400 primers with special flanking regions or have over 400 wells for ASO |
|
|
Term
| what are the symptoms of PKU |
|
Definition
|
|
Term
| how many exons could have a PKU causing mutation |
|
Definition
|
|
Term
| what types of mutations could cause PKU |
|
Definition
| mostly missense and some splice, nonsense, insertions, deletions |
|
|
Term
| describe how to do RFLP analysis to determine PKU |
|
Definition
| collect DNA from many family members including 1 person with the disease and the patient, find a RFLP marker that is near the disease site, do a southern blot on the RFLP marker and compare the patient with the normal, carriers, and affected family members to find the patient's result |
|
|
Term
| what kind of mutation cause myotonic dystrophy and of what gene |
|
Definition
| 3' non-coding trinucleotide repeat of a protein kinase gene |
|
|
Term
| what is the most common adult muscular dystrophy |
|
Definition
|
|
Term
| describe how to do RFLP comparison to determine muscular dystrophy |
|
Definition
| digest part of the RFLP and get an identifiable sequence, compare to family members who are affected or not, the mutant allele may be different in each person but you compare to the family members so you can see what normal looks like in that family |
|
|
Term
| what happens to trinucleotide repeats over time |
|
Definition
| they get bigger with each generation |
|
|
Term
| why can we do PCR on a trinucleotide repeat |
|
Definition
| PCR can flank the expansion region but when it gets too big it becomes difficult for PCR to amplify the region |
|
|
Term
| what techniques do you use to detect HIV |
|
Definition
| immunoassays: ELIZA and western blot |
|
|
Term
| why is it difficult to detect HIV early |
|
Definition
| because it takes years for the symptoms to develop because it takes a long time for antibodies to form |
|
|
Term
| at what point can you test for HIV |
|
Definition
| around 6 months after infection there should be enough antibodies, but you can do it earlier but retest after 6 months |
|
|
Term
| how to use ELIZA to test HIV |
|
Definition
| bind proteins to the wells and add the HIV antibody, add the sample to the wells, if there is an HIV antibody there will be a reaction causing color change |
|
|
Term
| why do we also do a western blot to test for HIV |
|
Definition
| ELIZA is super sensitive and could give a flase positive so you want to test the protein to make sure it is the right size and is HIV |
|
|
Term
| how do you do a western blot to test for HIV |
|
Definition
| do electrophorsis to seperate sample, probe for a protein reaction and verify the protein by size |
|
|
Term
| how has PCR revolutionized HIV testing |
|
Definition
| test can be done immediatly because you need less sample, you can PCR for the provisus to test time now, you can do reverse transcription PCR for HIV itself, you can monitor HIV over time (quantative) |
|
|
Term
| how is paternity testing done |
|
Definition
| design a primer to flank VnTR molecular fingerprint and amplify, stain for any DNA present (no probe) and compare to family |
|
|
Term
| what is the paternity index |
|
Definition
| because VNTRs are not perfect between family members different states require you to test a different amount of VNTRs before making a decision on paternity |
|
|
Term
|
Definition
| basic unit of inheritence |
|
|
Term
|
Definition
| location of a gene on a chromosome |
|
|
Term
|
Definition
| alternative form of a gene at a locus |
|
|
Term
|
Definition
| genetic constitution of a person |
|
|
Term
|
Definition
| observed expression of a genotype |
|
|
Term
|
Definition
| identical allels on each locus of a chromosome pair |
|
|
Term
|
Definition
| different allels on each locus of a chromosome pair |
|
|
Term
|
Definition
| condition in homozygotes and heteroxygotes where only one copy of the gene is needed for the phenotype |
|
|
Term
|
Definition
| condition in homozygotes and heteroxygotes where two copies of the gene are needed for the phenotype |
|
|
Term
|
Definition
|
|
Term
| how many autosomes do we have |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| 2 copies of each chromosome |
|
|
Term
|
Definition
| 1 copy of each chromosome |
|
|
Term
|
Definition
|
|
Term
|
Definition
| sex cell, haploid egg or sperm |
|
|
Term
|
Definition
| single gene mutated, transmitted in simple patterns |
|
|
Term
| what are the types of single gene disorders |
|
Definition
| autosomal, recessive, X linked |
|
|
Term
|
Definition
| deviation in number of chromosomes |
|
|
Term
| structural chromosome abnormality |
|
Definition
| more, less, or wrong chromosome info |
|
|
Term
|
Definition
| multiple genes and non-genetic (enivormental) influences |
|
|
Term
| what shape and color is an asympatmatic male |
|
Definition
|
|
Term
| what shape and color is an asymptamatic female |
|
Definition
|
|
Term
| what shape and color is an symptamatic male |
|
Definition
|
|
Term
| what shape and color is an symptamatic female |
|
Definition
|
|
Term
| what shape and color is an dead male |
|
Definition
| square with line through it |
|
|
Term
| what shape and color is an dead female |
|
Definition
| circle with line through it |
|
|
Term
| what shape shows two are mating |
|
Definition
| line between circle and square |
|
|
Term
| what shape shows two related people are mating |
|
Definition
| 2 lines between circle and square |
|
|
Term
| what shape shoes dizygotic twins |
|
Definition
| single line that branches from parents that splits to the two twins |
|
|
Term
| what shape shows monozygotic twins |
|
Definition
| triangle with points being parents and two kids |
|
|
Term
| how can you tell by a pedigree that a disease is autosomal dominent |
|
Definition
| affected person in every generation, always one affected parent, affects either sex, has male to male transmission |
|
|
Term
| what proteins are associated with autosomal dominate disorders |
|
Definition
|
|
Term
| what diseases are autosomal dominate |
|
Definition
| familial hypercholsterlemia, huntingtons, myotonic dystrophy, neurofibromastosis type 1, osteogenesis imperfecta, marfans syndrome |
|
|
Term
| what is the recurrance risk |
|
Definition
| probability of disease being passed to offspring with each reproductive event not affecting the occurance of another in the data |
|
|
Term
| when determining recurrance risk in autosomal dominent disorders what does an upper case letter mean |
|
Definition
| dominent allele (nothing to do with mutant or not) |
|
|
Term
| when determining recurrance risk in autosomal dominent disorders what does an lower case letter mean |
|
Definition
| recessive allele (nothing to do with mutant or not) |
|
|
Term
| what is the most common autosomal dominant cross, what is the percentage of having affected children |
|
Definition
|
|
Term
| in a pedigree, what trends show it is an autosomal recessive disorder |
|
Definition
| affected person normally has unaffected parents, either sex affected, both parents are at least carriers, male to male transmission, skipping of generations |
|
|
Term
| what proteins are involved in autosomal recessive disorders |
|
Definition
|
|
Term
| what are some autosomal recessive disorders |
|
Definition
| sickle cell anemia, cystic fibrosis, pku, tay-sacs |
|
|
Term
| what familial situation usually causes autosomal recessive disorders |
|
Definition
|
|
Term
| what type of genetic cross is commonly involved in autosomal recessive diseaes, what percent of the children are affected |
|
Definition
| Aa x Aa giving a 25% chance of disease |
|
|
Term
| when doing a cross for chance of inheritence with an autosomal recessive disorder, what does a lower case letter signify |
|
Definition
|
|
Term
| what are the two categories of diseases associated with the X gene |
|
Definition
| x-linked dominent and x-linked (recessive) |
|
|
Term
| what type of genetic disease is fragile x |
|
Definition
| it is considered to be x-dominent sometimes and x-linked others |
|
|
Term
| who is affected by x linked disorders |
|
Definition
|
|
Term
| in a pedigree, how can you tell a disorder is x linked |
|
Definition
| usually unaffected parents, male inherits diseased allele from mom, no male to male transmission |
|
|
Term
| what are some x-linked diseases |
|
Definition
| duchene and becker muscular dystrophy, lesh-nyhan syndrome, glucose-6-phosphate dehydrogenase deficiency, hemophilia A and B, menches |
|
|
Term
| what is the most common genetic cross involved in x-linked diseases, what percent of children will be affected |
|
Definition
|
|
Term
| what does mitochondrial DNA encode for |
|
Definition
| 13 proteins, 2 rRNA, 22 tRNA |
|
|
Term
| on a pedigree, how can you tell if a disorder is mitochondrial |
|
Definition
| affected female affects all children, affected male affects none of the children, males and females affected, |
|
|
Term
| what diseases are due to mitochondrial inheritance |
|
Definition
| leber's hereditary optic neuropathy, neuropathys, myopaths, cardiomyopaths |
|
|
Term
| how do you calculate the risk of recurrance in mitochondrial diseases |
|
Definition
| you don't it does not follow mendilian genetics |
|
|
Term
| what are the symptoms of leber's hereditary optic neuropathy |
|
Definition
| blindness, rapid, irreversable, begins in central field, around age 30, optic atrophy |
|
|
Term
| what is wrong with the proteins in osteogenesis imperfecta |
|
Definition
| defect in structural proteins |
|
|
Term
| what diseases have a defecit in regulatory proteins |
|
Definition
| familial hypercholsterloemia, myotonic dystrophy |
|
|
Term
| what is a gain of function disorder |
|
Definition
| normal protein becomes too toxic |
|
|
Term
| what disease causes a gain in protein function, what does it affect |
|
Definition
| huntington disease causes toxic effects to neurons |
|
|
Term
| why type of inheritence is neurofibromatosis type 1 |
|
Definition
|
|
Term
| what is mutated in neurofibromatosis type 1 |
|
Definition
| regulatory protein involved in controlling the cell cycle |
|
|
Term
| what are the symptoms of neurofibromatosis type 1 |
|
Definition
| cafe-au-lair spots, multiple neurofibromas, axillary freckling, lisch nodules in eye, variable expression |
|
|
Term
| what type of inheritance is marfans syndrome |
|
Definition
|
|
Term
| in marfan syndrome what is mutated, in what major areas is it located |
|
Definition
| fibrillin mutation, ECM and connective tissue |
|
|
Term
| what are the symptoms of marfan syndrome |
|
Definition
| thin long limbs, long fingers, hypermobile joints, myopia, detached lens, aortic aneurysm |
|
|
Term
|
Definition
| 1 mutation affects multiple organ systems, common |
|
|
Term
| what disease is an example of pleiotropy |
|
Definition
|
|
Term
| what type of inheritance is thalassemia |
|
Definition
|
|
Term
| what gene is affected in alpha-thalessemia, what is the result |
|
Definition
| insufficient synthesis of alpha chain of hemaglobin, beta globin acclumulates |
|
|
Term
| what gene is affected in beta-thalessemia |
|
Definition
| insufficient synthesis of beta chain of hemaglobin, alpha chain accumulates |
|
|
Term
| where in the world are thalassemia diseases common |
|
Definition
| mediterian sea, africa, southeast asia |
|
|
Term
| describe the globin content in a normal hemaglobin |
|
Definition
| 2 beta globin from 2 normal genes make 2 beta chains, 4 alpha globin from 2 copies of 2 adjacent genes make 2 alpha chains |
|
|
Term
| what chromosome is alpha globin on |
|
Definition
|
|
Term
| what chromosome is beta globin on |
|
Definition
|
|
Term
| so if there are more alpha globin genes and less beta globin why isnt there always more alpha globin |
|
Definition
| the body accounts for this and we still get equal production |
|
|
Term
| describe the globin content of a fetal hemaglobin |
|
Definition
| 2 gamma chains and 2 alpha chains |
|
|
Term
| what makes fetal hemaglobin functionally different from adult |
|
Definition
| it has a higher affinity for oxygen so it can pull oxygen from the mother;s hemaglobin |
|
|
Term
| when does fetal hemaglobin go away, what replaces it |
|
Definition
| from 6 mo - 2 yrs old it decreases and is replaced by beta globin |
|
|
Term
| when someone has beta thalasemia, they have a decrease in beta Hb and increase in alpha Hb, why can't they use use 4 alpha Hb and be fine |
|
Definition
| a Hb with 4 alpha Hb chains is insoluble and percipitates and is removed by the spleen and other blood cleaning organs due to 'damage' |
|
|
Term
|
Definition
|
|
Term
| what does it mean when said that beta-thalasemia has compounded anemia |
|
Definition
| beta globin is decreased giving anemia, and the 4 alpha globin Hb that took its place are removed giving further anermia |
|
|
Term
| describe the genes of a beta thalasemia carrier |
|
Definition
| 1 normal copy and 1 mutated |
|
|
Term
| describe the genes of a person affected with beta thalassemia |
|
Definition
| 2 mutated copies of the gene with various intensities B0 or B+ and combinations of these intensities |
|
|
Term
| what is a B0 (beta o) mutation |
|
Definition
| total absence of the functional B globin in that copy of the gene |
|
|
Term
| what is a B+ (beta +) mutation |
|
Definition
| leads to reduct beta globin but it is still normal |
|
|
Term
| what may be some of the reasons for a beta + mutation |
|
Definition
| may be a problem with the promoter, not getting sufficient promotion of transcriptioon but do get some |
|
|
Term
| what are the symptoms of thalassemia minor |
|
Definition
| usually asymptamatic of have mild anemia which may be mistaken for Fe deficiency anemia. |
|
|
Term
| how do you diagnose thalassemia minor |
|
Definition
| hemaglobin electrophoresis or blood work |
|
|
Term
| describe the genes of someone with beta thalassemia minor |
|
Definition
| carrier, one affected gene |
|
|
Term
| what are the symptoms of beta thalassemia major |
|
Definition
| severly reduced or no Hb production, severe anemia, hepatosplenomegaly, skeletal deformities especially in face and scull, bone marrow expansion, increased systemic Fe accumulates in liver and heart |
|
|
Term
| why is beta thalassemia not seen in babies |
|
Definition
| because they dont use beta globin until 6 mo old, they use gamma |
|
|
Term
| why is there hepatosplenomegaly in b-thalassemia |
|
Definition
| because the liver and spleen are trying to make new RBC and are getting rid of so many that they swell |
|
|
Term
| what does someone with b-thalassemia get skeletal and face deformities |
|
Definition
| because the bone marrow swells due to trying to make so many RBC |
|
|
Term
| how do you treat thalassemia major |
|
Definition
| regulat blood transfusions (every 2-4 weeks) combined with Fe chelation therapy, bone marrow transplants, potential gene therapy |
|
|
Term
| what are the symptoms and treatment of thalassemia intermedia |
|
Definition
| vary a lot, defined on clinical symptoms, treat with occasional blood transfusions |
|
|
Term
| what is gamma-globin synthesis continued into adulthood |
|
Definition
| turning the gene on could kill of b-thalasemia but people could have a hard time releasing O2, so less athletics, or could kill baby if pregant becase mom is stealing all the o2 |
|
|
Term
| in regard to genes, what usually causes alpha-thalassemia |
|
Definition
| usually due to missing genes, classified by how many are missing |
|
|
Term
| in alpha-thalassemia, what is the phenotye of aa/aa, what are the symptoms |
|
Definition
|
|
Term
| in alpha-thalassemia, what is the phenotye of -a/aa, what are the symptoms |
|
Definition
|
|
Term
| in alpha-thalassemia, what is the phenotye of --/aa, what are the symptoms |
|
Definition
| alpha-thalassemia trait, symptoms like thalassemia minor or are asymptmatic |
|
|
Term
| in alpha-thalassemia, what is the phenotye of -a/-a, what are the symptoms |
|
Definition
| alpha-thalassemia trait, symptoms like thalassemia minor or are asymptmatic |
|
|
Term
| in alpha-thalassemia, what is the phenotye of --/-a, what are the symptoms |
|
Definition
| hemaglobin H (HbH) disease, symptoms like thalassemia intermedia |
|
|
Term
| in alpha-thalassemia, what is the phenotye of --/--, what are the symptoms |
|
Definition
| hydrops fetalis, cannot support life because babies need alpha thalasemia unline beta |
|
|
Term
| what does hydrops fetalis mean |
|
Definition
| not specific to alpha-thalassemia, general term for death in utero with adema and swelling |
|
|
Term
| what happens in utero to the globin molecule when someone has alpha-thalassemia |
|
Definition
| gamma-globin forms tertameres (Hb Bart) |
|
|
Term
| what happens in utero when someone has alpha thalassemia with 1 copy of alpha globin |
|
Definition
| evuntally B-globin tetramere HbH forms |
|
|
Term
| what is the difference between HbH / HbBart and the beta-globin tetramere, what differences does this cause in the symptoms |
|
Definition
| they are less toxic which is why someone with any alpha globin at all has less severe symptoms that someone with b-thalassemia |
|
|
Term
| in regards to x-linked genes, what is the word that classifies males, what does this mean |
|
Definition
| hemizygos, they only need one copy of the gene to show symptoms wether it is dominent or recessive |
|
|
Term
| what gene is damaged in hemophellia a |
|
Definition
|
|
Term
| what gene is damaged in hemophelia b |
|
Definition
|
|
Term
| what type of mutations can cause hemophelia |
|
Definition
| deletions, nonsense, DNA inversions |
|
|
Term
| what cellular difference leads to difference severities in the symptoms of hemophelia |
|
Definition
| different mutations leading to different levels of the clotting factors in the body |
|
|
Term
| how can you tell the differences, in regard to symptoms, between hemophelia a and b |
|
Definition
| they have the same symptoms so you need to do a blood test or gene sequencing |
|
|
Term
| is hemophelia common or rare |
|
Definition
|
|
Term
| what type of hemophelia is more common |
|
Definition
|
|
Term
| what are the symptoms of hemophelia |
|
Definition
| prolonged bleeding, intercranial hemorraging, easy bruising, hemarthorsis |
|
|
Term
| what is hemophelia often mistaken for |
|
Definition
|
|
Term
| what signs of hemophelia are often noticed at birth |
|
Definition
| too much bleeding during circmucision or cutting umbilical cord, intercranial hemmorage that can cause death |
|
|
Term
|
Definition
|
|
Term
| what is the most frequent cause of death in people with hemophelia, why |
|
Definition
| AIDs, because treatment is factor replacement therapy and we used to use concentrated human plasma and during purification viruses are not eliminated |
|
|
Term
| why is AIDs less of a problem for hemophelia patients now |
|
Definition
| because we have better screening processes and are moving towards recombinent clotting factors and potential gene therapy |
|
|
Term
| what worries do people with hemophelia still have today when doing factor replacement therapy |
|
Definition
| some viruses not eliminated or tested for still, like hepititis |
|
|
Term
| in duchenne and becker muscular dystrophy what gene is affected |
|
Definition
| dystrophin gene in both diseases |
|
|
Term
| in duchenne and becker muscular dystrophy, they affected gene causes problems in cells of which areas |
|
Definition
| cytoplasm of muscle (all kinds) and some neuro tissue |
|
|
Term
| why does the gene for duchenne and becker muscular dystrophy have a higher mutation rate and get new mutations |
|
Definition
|
|
Term
| why type of mutation causes duchenne muscular dystrophy |
|
Definition
| frameshift insertion/deletion, also leads to a trunkated protein due to the potential of an early stop codon |
|
|
Term
| compare duchenne muscular dystrophy to myotonic muscular dystrophy in severity and frequency |
|
Definition
| duchenne muscular dystrophy is more common overall and more sever, myotonic is only the most common adult muscular dystrophy |
|
|
Term
| what are the symptoms of duchenne muscular dystrophy |
|
Definition
| apparent at 5 yrs, 10-12 years wheelchair, muscle atrophy, progressive, cognative impairment, death due to decreased respiratory function causing infections and decreased cardiac function around 20 yrs |
|
|
Term
| what type of deletion is becker muscular dystrophy |
|
Definition
| non-frameshift insertion/deletion |
|
|
Term
| what is the differences in the gene for becker muscular dystrophy vs duchenne |
|
Definition
| the gene makes a partially functional protein causing more mild symptoms |
|
|
Term
| what are the symptoms of becker muscular dystrophy |
|
Definition
| same general progression as duchenne but takes longer, onset is about 11 yrs and death 42 |
|
|
Term
| what is the treatment for duchanne and becker muscular dystrophy |
|
Definition
| only therapy, gene therapy has show potential in animal models but the large gene makes things difficult |
|
|
Term
| what is another name of x-inactivation |
|
Definition
|
|
Term
| why do we need x-inactivation |
|
Definition
| because gemales have 2 X and males only 1, so in theory, females would make double of all the proteins which they do not need |
|
|
Term
|
Definition
| where one chromosome in females is shut off and not available for transcription |
|
|
Term
| what is the inactivated x chromosome called |
|
Definition
|
|
Term
| how are the genes of a barr body shut off |
|
Definition
|
|
Term
| in what phase are the nuclei of a barr body when they are shut off |
|
Definition
|
|
Term
| at what stage does the cell shut off the barr body duriing the development |
|
Definition
|
|
Term
| how does the cell decide which X chromosome to shut off during x-inactivation |
|
Definition
| it is random but after the 100 cells choose, all of their decendents will have the same one shut off |
|
|
Term
| what is ment when said that x-inactivation is incomplete |
|
Definition
| the entire barr body isn't shut off, about 10% is able to be transcribed |
|
|
Term
| what does incomplete x-inactivation explain |
|
Definition
| why some females show traits of mutant with only one copy mutated and one normal gene and why the symptoms are less severe (because they only have one X it makes it almost like they can get recessive x-linked diseases like males, but because they are females and do have normal genes it is less severe) |
|
|
Term
| why does it matter which x is shut off in each cell during x-inactivation |
|
Definition
| some come from mom and some come from dad and the one left on is randomly chosen, this gives potential for good genes to be deactivated and bad ones to stay active (or vice versa). unlucky choosing can produce more bad genes than good ones even though the female would normally be an asymptamatic carrier and they will then express the disease |
|
|
Term
| how can severe hemophelia occur in females |
|
Definition
| because unlucky shutting off of the barr body can make a carrier express more of the mutant genes, giving them the full symptoms anyways |
|
|
Term
| what type of mutation is fragile x |
|
Definition
| trinucletide repeat expansion in the 5' non coding region |
|
|
Term
| what are the symptoms of fragile x |
|
Definition
| long face, large mandible, large everted ears |
|
|
Term
| what is the most common know cause of autism |
|
Definition
|
|
Term
| what is the most common inherited mental retardation |
|
Definition
|
|
Term
| why can't fragile x be considered x-linked dominent |
|
Definition
| dominent should have 2x as many females as males affected and there are quite of bit of females affected but not more than males |
|
|
Term
| why can't fragile x be considered x-linked recessive |
|
Definition
| because recessive means that almost no females should be affected and quite a few are |
|
|
Term
| when a female gets fragile x, how do her symptoms differ |
|
Definition
| they are more variable and less severe |
|
|
Term
| how many fragile x mutations does a female with fragile x have, explain your answer |
|
Definition
| 1 or 2. they can get symptoms with only one because of the barr body situation where it makes only one x chromosome anyways, or they can have two |
|
|
Term
| what type of x-linked disease is fragile x most likley to be in conclusion, why |
|
Definition
| x-linked recessive, because you can't say dominent/recesive when your only expressing one gene as it has seen to be the case in all males and most all females with fragile x |
|
|
Term
| What disorder type is delayed age of onset a symptom of |
|
Definition
|
|
Term
| What disorders have a delayed age of onset |
|
Definition
| Huntingtons, myotonic dystrophy |
|
|
Term
| What is locus heterogeneity |
|
Definition
| Same phenotype is caused by mutations at different loci |
|
|
Term
| What disease has locus heterogeneity, in regards to inheritance what does this cause |
|
Definition
| Elhers danlos syndrome, several inheritance patterns |
|
|
Term
| What types of instance can elhers danlos have |
|
Definition
| Autosomal dominant and recessive, x linked |
|
|
Term
| What is the mutation in elhers danlos autosomal dominant |
|
Definition
|
|
Term
| What is the mutation in elhers danlos autosomal recessive, what process does this disrupt |
|
Definition
| Mutation in Lysol hydroxylase, processing collagen |
|
|
Term
| What is the mutation in elhers danlos x linked recessive, what does this cause |
|
Definition
| Mutation in copper binding protein gene on the x chromosome leading to reduced copper in serum (copper is involved in lysyloxidase which causes cross linking in collagen) |
|
|
Term
| how do all diseases start |
|
Definition
|
|
Term
| what are the characteristics of a disease that in most cases comes from a new mutation |
|
Definition
| high mortality or decreased fertility |
|
|
Term
| what categories of disorders often come from a new mutation (dominent, recessive, autosomal, X) |
|
Definition
| autosomal dominent, x-linked recessive |
|
|
Term
| what disease did we talk about is an example of a new mutation, what inhertience model is it |
|
Definition
| duschenne muscular dystrophy, x-linked |
|
|
Term
|
Definition
| most recent generations have earlier onset and more severity |
|
|
Term
| what mutation is associated with anticipation, how does the aspects of this mutation correlate with the definition of anticipation |
|
Definition
| trinucleotide repeats, more repeats means more severity, there are more repeats with each generation |
|
|
Term
| what diseases are and example of anticipation |
|
Definition
| myotonic dystrophy, huntington, fragile x |
|
|
Term
| what do we use to evaluate population genetics |
|
Definition
| hardy weinberg equlibrium |
|
|
Term
| what are the assuptions that make the hardy weinberg equlibrium possible |
|
Definition
assume 2 alleles (p and q)
the frequency total is 100%: so p + q = 1 |
|
|
Term
| how do you determine the frequency of the genotype qq |
|
Definition
|
|
Term
| how do you determine the frequency of the genotype pp |
|
Definition
|
|
Term
| how do you determine the frequency of the genotype pq |
|
Definition
|
|
Term
| what are the factors that affect genetic variation |
|
Definition
| mutations, natural selection, heterozygote advantage, genetic drift, gene flow |
|
|
Term
| how much do mutations affect the genetic variation |
|
Definition
| it is different in every population, in humans not that much |
|
|
Term
| what is natural selection |
|
Definition
| influce on gene frequency by selecting for survival or fertility making disease genes more rare |
|
|
Term
|
Definition
| natural selection for fertility |
|
|
Term
| which types of genes are exposed to selection more often |
|
Definition
|
|
Term
| why are recessive genes exposed to selection less often |
|
Definition
| because they are often hidden in the heterozygote |
|
|
Term
| what is the heterozygote advantage |
|
Definition
| when a heterozygote mutation is selected for because it prevents other, worse diseases |
|
|
Term
| what are examples of the heterozygote advantage |
|
Definition
| sickle cell helps milaria, thallesemia helps malaria, cystic fibrosis may help with typhoid fever, G6PD helps malaria |
|
|
Term
| why in sickle cell is the carrier not affected |
|
Definition
| because in the carrier the plasmodium survives poorly giving malaria resistance without too many side effects |
|
|
Term
|
Definition
| in populations with a finite small size rare genes are present because they founders had them and there wasn't much room for genetic variance |
|
|
Term
| what is another name fo genetic drift |
|
Definition
|
|
Term
| what is a disease that is an example of the founder effect |
|
Definition
|
|
Term
| what type of inheritence is ellis van cerveld |
|
Definition
|
|
Term
| what are the symptoms of ellis van cerveld |
|
Definition
| usually in old order amish communities, polydactyly (short limbed dwarfism) |
|
|
Term
| what gene is effected in ellis van cerveld |
|
Definition
|
|
Term
|
Definition
| the exchange of genes amoug populations |
|
|
Term
| what is the cause of methemoglobinemia |
|
Definition
| elevated Met Hb in the blood which has oxidized Fe so it cannot pick up oxygen as well |
|
|
Term
| what are the symptoms of methemoglobinemia |
|
Definition
| blue skin, blood that upon introduction to air stays brown |
|
|
Term
| what happens to normal deoxygenated blood upon esposure to air |
|
Definition
| it immediatly reoxygenates and turns red |
|
|
Term
| what is another name for methemoglobinemia |
|
Definition
|
|
Term
| normal people do get met hb, why are they not blue |
|
Definition
| because normally the body makes enzymes to reduce it |
|
|
Term
| how can someone aquire methemoglobinemia |
|
Definition
| oxidative stress: drugs, antibiotics, thromethoprimcane, anaesthetics, compounds with nitrates |
|
|
Term
| why are infants under 6 mo more prone to methemoglobinemia, what should they stay away from because of this risk |
|
Definition
| they do not have adult levels of the enzymes that combat met hb yet, nitrates ingested in food / water can cause it |
|
|
Term
| what is defective in congenital methemoglobinemia |
|
Definition
| decreased NADH met hb reductace which normally reduces Fe so it can pick up oxygen, increased HbM and HbH. thee enzyme is active just not efficient |
|
|
Term
| what is another name for NADH met hb reductase |
|
Definition
|
|
Term
| what are diseases with congenita methemoglobinemia |
|
Definition
| pyrivate kinase deficiency, G6PDH deficiency |
|
|
Term
| how is methemoglobinemia treated |
|
Definition
| methlyine blue, electron donor reduces Fe back to normal so it can pick up oxygen. gives blue pee |
|
|
Term
| what is the mutation in hippel lindau syndrome |
|
Definition
| nutation in tumor supressor, |
|
|
Term
| many times hippel lundeau is cause by what type of tumor |
|
Definition
| pheochromocytomas: tumors in the adrenal gland |
|
|
Term
| what symptoms does a pheochromocytomas cause, why |
|
Definition
| explosive temper, due to excessive production of adreniline |
|
|
Term
| what genetic trend is lynch syndrome and example of |
|
Definition
|
|
Term
|
Definition
| multiple of 23 chromosomes |
|
|
Term
| what are the types of euploidy |
|
Definition
| haploid, diploid, triploid, tetraploidy |
|
|
Term
| what types of cells are haploid |
|
Definition
|
|
Term
| what types of cells are diploid |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| how does tetraploidy happen |
|
Definition
| 2 sperm fertilize one egg |
|
|
Term
| what are the symptoms of tetraploidy |
|
Definition
| usually spontanous abortion, some born live but die due to heart and CNS issues |
|
|
Term
|
Definition
| derivation from euploidy number of chromosomes, loss or gain of chromosomes |
|
|
Term
|
Definition
| one copy of specific chromosome |
|
|
Term
| what are the symproms of monosomy |
|
Definition
| lethal, unless caused by one sex chromosome |
|
|
Term
|
Definition
| three copies of a chromosome |
|
|
Term
| what is the life expectancy of someone with autosomal and x-linked trisomy |
|
Definition
| can potentially survive, sex chromosome trisomy have more potential to be normal |
|
|
Term
| what does the body tolerate better: more or less genetic information |
|
Definition
|
|
Term
| do chromosomal abnormalities usually have a high life expectancy |
|
Definition
|
|
Term
| what causes monosomy or trisomy |
|
Definition
| nondisjunction in meiosis 1 or 2 |
|
|
Term
| what can increase the odds of monosomy or trisomy |
|
Definition
| age, the tipping point is approx age 35 |
|
|
Term
| what chromosome numbers are there in the cells that are the final product of non dysjunction in meiosis 1 |
|
Definition
| 2 cells with n+1 chromosomes |
|
|
Term
| what chromosome numbers are there in the cells that are the final product of non dysjunction in meiosis 2 |
|
Definition
| 2 normal cells, 1 cell with n+1 |
|
|
Term
| why does nondysjunction changes increase with age |
|
Definition
| egg cells are stuck in prophase 1 until ovulation, the chromosomes become more adherent to eachother and less likley to disconnect |
|
|
Term
| what is the symbol for a normal karyotype |
|
Definition
|
|
Term
| what is the karyotype for trisomy 21 |
|
Definition
|
|
Term
| what is the most common autosomal trisomy |
|
Definition
|
|
Term
| what is the most common genetic cause of mental retardation |
|
Definition
|
|
Term
| what are the symptoms of trisomy 21 |
|
Definition
| short stature, flat profile, upward slanting of the eyes, depressed nasal bridge, upper eye lids sags, displastic ears, congential heart defects, respitory infections, abnormal immune system, increased lukemia risk, early alzhimers |
|
|
Term
| what is another name for trisomy 18 |
|
Definition
|
|
Term
| what is the karyotype for edwards syndrome |
|
Definition
|
|
Term
| what are the symptoms of trisomy 18 |
|
Definition
| predominent occiput, small mouth and ears, small babies, rocker bottom feet, clenched fists, overlaping fingers, congenital heart problems, organ defects |
|
|
Term
| what is another name for trisomy 13 |
|
Definition
|
|
Term
| what is the karyotype for patu syndrome |
|
Definition
|
|
Term
| what are the symptoms of trisomy 13 |
|
Definition
| oral facal cleft, small eyes, polydactyly, congenital heart defects, organ defects |
|
|
Term
| in sex chromosome aneuploidy what must there at the least be to survive |
|
Definition
|
|
Term
| what is usually more severs, sex chromosome anruploidy or autosome aneuploidy |
|
Definition
|
|
Term
| what is the karyotype of klinefelters |
|
Definition
|
|
Term
| what are the symptoms of klinefelters |
|
Definition
| atrophy of seminal tubules, small testis, long arms and legs, decreased secondary sex characteristics, gynecomastia (brests), decreased IQ |
|
|
Term
| what determines the severity of klinefelters |
|
Definition
| radio of estrogen to testosterone |
|
|
Term
| what is the karyotype of tunder syndrome, the most common one |
|
Definition
|
|
Term
| describe the variations in chromosomes / karyotypes that turner syndrome has |
|
Definition
| some have 1 X, some have 1 X with missing parts, some have mosacis |
|
|
Term
|
Definition
| a combination of 46XX in some cells and 45X in others |
|
|
Term
| what are the symptomes of turner syndrome |
|
Definition
| short, webbed neck, widly spaced nipples, lymphedema of ankles and wrists, broad chest, sterility due to 45X |
|
|
Term
| what are te symptoms of a 47XYY |
|
Definition
| normal mostly but tall, social issues prone to hyperactivity, lower IQ |
|
|
Term
| what are the symptoms of 47XXX |
|
Definition
| essentially normal, almost never diagnosed, increased chance of psycharitic problems like schizophrenia |
|
|
Term
| what is a structural chromosome abnormality |
|
Definition
| missing, added or switched piece of a chromosome |
|
|
Term
| in theory what can gene therapy treat |
|
Definition
| infections that do not have a cure |
|
|
Term
| in one sentence, tell how gene therapy works |
|
Definition
| transfer specific genetic information (usually DNA) into patient to treat disease |
|
|
Term
| potentially in the future, what could gene therapy treat |
|
Definition
| genetic diseases (monogeme) and cancer |
|
|
Term
| what is somatic gene therapy |
|
Definition
| gene delivered only to somatic cells, not effect to germline. |
|
|
Term
| what is the type of gene therapy used in people today |
|
Definition
|
|
Term
| what is germline gene therapy |
|
Definition
| affects somatic and germline or only germline cells |
|
|
Term
| what makes germline gene therapy different from somatic |
|
Definition
| affects germline, perminate, heritable, ethical issues |
|
|
Term
| what is germline gene therapy currently used for |
|
Definition
| inducing human diseases in lab animals to use them in experiments, nothing in humans |
|
|
Term
| to have successful gene therapy what do you need |
|
Definition
| efficient gene delivery system, theraputic genes |
|
|
Term
| what is the function of a gene delivery system |
|
Definition
| get the gene to the right cell, the the gene inside the cell, express the gene |
|
|
Term
| what gene delivery system is most common in gene therapy in humans |
|
Definition
|
|
Term
| why do we use viral gene delivery systems |
|
Definition
| viruses already have the machinery to get in a cell with genetic material and integrate it into human DNA |
|
|
Term
| how can we use a viral gene delivery system when it is well... a virus |
|
Definition
| the viral pathogen genes are removed / blocked but the genes used to get in the cell and integrate DNA are not. despite this it could still cause problems |
|
|
Term
| what is transient expression |
|
Definition
| gene inserted through gene therapy is not replicated through normal cell gene replication |
|
|
Term
| if a gene has transient expression, how can you make gene therapy successful anyways |
|
Definition
|
|
Term
| what are some issues that can nix your gene therapy efforts even though you have a good gene delivery system |
|
Definition
| new gene knocks out function of another gene when inserted, difficult to control expression, immune system may reject the cells with the gene (apoptosis) |
|
|
Term
| what are the three most common vector systems used in gene therapy |
|
Definition
| retroviral, adenovirus, non-viral |
|
|
Term
| what are the benifits of using retrovirus vectors in gene therapy |
|
Definition
| high efficiency transduction into cells infecting a lot of them, inserts into the chrosomosone (not transient) |
|
|
Term
| what are the negatives of using retrovirus vectors in gene therapy |
|
Definition
| need to insert into dividing cell, mutations due to insertion, size limits of gene, risk of infection |
|
|
Term
| what are the benifits of using adenovirus vector during gene therapy |
|
Definition
| good transduction into cells and affects lots of cells, don't have to wait for dividing cell, broad range of target cells, does not insert into chromosome |
|
|
Term
| what are the negatives of using adenovirus vector in gene therapy |
|
Definition
| transient expression, immune rejection possible, become resistant over time, risk of infection |
|
|
Term
| what are the benifits of using a non-viral vector in gene therapy |
|
Definition
| no infection risk, decreased immune response, synthetic, no size limitation |
|
|
Term
| what are the negatives of using non-viral vector in gene therapy |
|
Definition
| low efficiency getting into and infecting cells, limited target cell possibilities, transient expression |
|
|
Term
| what is gene augmentation therapy |
|
Definition
| give extra copy of a normal gene |
|
|
Term
| what does gene augmentation therapy treat |
|
Definition
|
|
Term
| explain targeted killing of specific cells as a gene therapy |
|
Definition
| toxic gene is delivered or expressed only in bad cells (like cancer cells) |
|
|
Term
| explain the gene therapy that uses target inhibition of gene expression |
|
Definition
| at level of DNA, RNA, or protein block transcription, translation, or degrate proteins |
|
|
Term
| what is targeted inhibition gene therapy used in |
|
Definition
| cancer gene therapy, some autosomal dominent diseases (huntingtons) |
|
|
Term
| explain how to do targeted gene mutation correction gene therapy in DNA |
|
Definition
1. target DNA
2. provide copy of normal sequence
3. replace mutated sequence piece (homologous recombination) |
|
|
Term
| explain how to do targeted gene mutation correction gene therapy in RNA |
|
Definition
|
|
Term
| what may be the only acceptable germline gene therapy |
|
Definition
| targeted gene mutation correction |
|
|
Term
| what is defficient in severe combined immunodeficiency disease, how ofted |
|
Definition
| adenosine deaminase 10% of cases |
|
|
Term
| what type of inheritance is severe combined immunodeficiency disease |
|
Definition
|
|
Term
| what process is affected in severe combined immunodeficiency disease |
|
Definition
| lymphocyte nucleotide metabolism do DNA replication is inhibited |
|
|
Term
| what is lacking in someone with severe combined immunodeficiency disease |
|
Definition
|
|
Term
| what is the symptom of severe combined immunodeficiency disease |
|
Definition
| suspectability to infection, must stay in a sterile enivornment |
|
|
Term
| what is the first example of successful gene therapy |
|
Definition
| severe combined immunodeficiency disease |
|
|
Term
| why did severe combined immunodeficiency disease not work in gene therapy |
|
Definition
| tried using stem cells instead but people developed lukemia |
|
|
Term
| list the steps of doing gene therapy on someone with severe combined immunodeficiency disease |
|
Definition
1. clone normal adenosine deaminase
2. put it in vector
3. isolate patient lymphocytes
4. transfect the lymphocyte with retrovirus vector
5. reverse transcriptase RNA to DNA
6. insert DNA into lymphocyte
7. inject lymphocyte into patient
8. expression of gene transforms lymphocyte regaining normal immune function |
|
|
Term
| what are the steps in cloning a mammal |
|
Definition
1. remove nucleus from egg cell
2. remove nucleus from animal you want to clone
3. inject nucleus into empty egg cell |
|
|
Term
| what are the issues with cloning mammals |
|
Definition
| mitochondrial DNA is not cloned, shortened temomeres may lead to shortened life span |
|
|
Term
| what is the job of a catalyst |
|
Definition
| increse the rate of a reaction without being changed itself |
|
|
Term
|
Definition
| reactions would be too slow |
|
|
Term
|
Definition
| usually protine, sometimes ribozymes |
|
|
Term
| what is the reactant called in an enzyme reaction |
|
Definition
|
|
Term
| what are some of the common ways to name enzymes |
|
Definition
| "substrate"-ase, "substrate + reaction description"-ase, "random other common name" |
|
|
Term
| describe the systemic way to name enzymes |
|
Definition
| "systemic name"-ase, "substrate: substrate systemic category"-ase |
|
|
Term
| what does a one way arrow in an enzyme reaction indicate |
|
Definition
| under normal human conditions the reaction goes in that direction, it could go the other way in reality but it isnt likley |
|
|
Term
| what does a double sided arrow in an enzyme reaction indicate |
|
Definition
| under normal human conditions, the reaction can go in either direction |
|
|
Term
|
Definition
| pocket of an enzyme that binds a substrate with amino acid compliments to it |
|
|
Term
|
Definition
| enzyme substrate complex: enzyme bound to substrate in a new conformation to facilitate catalysis |
|
|
Term
|
Definition
| enzyme product: dissociates into enzyme and product |
|
|
Term
| what is a way we can measure the catalytic efficiency |
|
Definition
|
|
Term
| what is the turn over number |
|
Definition
| number of molecules of substrate converted to product per enzyme per second |
|
|
Term
| what is the abreviation for turn over number |
|
Definition
|
|
Term
| how do enzymes display specificity |
|
Definition
| they only allow one or few substrates (similar structure), only do one type of reaction |
|
|
Term
|
Definition
| enzyme and its non-protein component |
|
|
Term
| what is an name for an active enzyme |
|
Definition
|
|
Term
|
Definition
| enzyme without its non protein component |
|
|
Term
| what is a name for an inactive enyme |
|
Definition
|
|
Term
|
Definition
| non-protein component of an enzyme made of metal |
|
|
Term
|
Definition
| non-protein component of an enzyme made of organic molecules |
|
|
Term
|
Definition
|
|
Term
| what are some examples of coenzymes |
|
Definition
| niacin makes NAD+, riboflavin makes FAD |
|
|
Term
| what is the point of the non-protein component of an enzyme |
|
Definition
| some enzymes need these (cofactor, coenzyme) to work |
|
|
Term
| how are enzymes regulated |
|
Definition
| activated or inhibited based on cell need |
|
|
Term
| what is the energy barrier |
|
Definition
| energy difference between that of reactants and a high energy intermediate that occurs during the formation of the product |
|
|
Term
| what does a high free energy of activation mean |
|
Definition
|
|
Term
| what do enzymes do to the free energy of activation |
|
Definition
| lower it, NOT change it. it accelerates the rate of the reaction but does not change the equlibruim |
|
|
Term
| desctibe the location of enzymes |
|
Definition
| specific subcellular compartments near organells, isolating substrates and products from competing reactions, organizes them into purposeful pathways |
|
|
Term
| what does it mean when we say that an enzyme "stabilizes the transition state" |
|
Definition
| holds substrate in conformation of high energy between substrate and product, increasing the concentration of the transition state and making it more likley that it will turn into product but giving chemical groups that participate in reaction to substrate and facilitate the form of the transition state |
|
|
Term
| what is the enzyme velocity |
|
Definition
| number of substrate that turns to product per unit time |
|
|
Term
| what is the normal units for enzyme velocity |
|
Definition
| micro mol / product / min |
|
|
Term
| what is maximal enzyme velocity |
|
Definition
| rate of enzyme catalization of a reaction with increasing substrate concentration until it reaches a max, all binding sites full, enzyme is saturated |
|
|
Term
| what is the hyperbolic curve |
|
Definition
| curve most enzymes follow. |
|
|
Term
| what are the axies of the hyperbolic curve |
|
Definition
| initial velocity (Vo) vs concentration of substrate |
|
|
Term
| what is the name of the principal that outlines the governing of the hyperbolic curve |
|
Definition
|
|
Term
| what does increasing the temperature around an enzyme do |
|
Definition
| increases velocity until a peak then decreases it making the molecules more high energy to breach activation energy until the peak which denatures |
|
|
Term
| what happens when an enzyme is denatured |
|
Definition
|
|
Term
| what is the normal temperature good for human enzymes |
|
Definition
|
|
Term
| how does pH affect enzymes |
|
Definition
| enzyme substrate needs certian groups protonated or unprotonated to form a catalytic enivornment, changes in pH can change protonation and ionic interactions denaturing the enzyme |
|
|
Term
| what is the optimum pH for an enzyme |
|
Definition
|
|
Term
| what is the reaction model in michaels menten reactions (word explination) |
|
Definition
| enzyme reversably combines with substrate to make complex that yields product and the free enzyme |
|
|
Term
| what is the reaction model in michaels menten reactions (reaction explination) |
|
Definition
|
|
Term
|
Definition
| the rate constant of the forward reaction in a michaels menten reaction when enzyme combines with substrate |
|
|
Term
|
Definition
| the rate constant of the reverse reaction in a michaels menten reaction when enzyme dissociates from substrate |
|
|
Term
|
Definition
| the forward only reaction where enzyme and substrate complex make enzyme and product in a mimchaels menten reaction |
|
|
Term
| in general, what does the michaels menten equation describe for us |
|
Definition
| how reaction velocity varies with substrate concentration at a given enzyme concentration |
|
|
Term
| what do we need to assume to make the michaels menten reaction work |
|
Definition
| amount of substrate bound by the enzyme at a given time is a small percentage of the total substrate aviable to drive the reaction forward and initial veolcity is used so there is no appreciable back reaction from product to substrate |
|
|
Term
|
Definition
| characteristic of an enzyme and particular substrate that relfects affinity of an enzyme for that substrate |
|
|
Term
|
Definition
|
|
Term
| what does a small km indicate |
|
Definition
| high affinity, so it takes a low concentration of substrate to reach 1/2 max velocity |
|
|
Term
| what does a big km indicate |
|
Definition
| low affinity, it takes lots of substrate to reach 1/2 max velocity |
|
|
Term
| how are max velocity and enzyme concentration related |
|
Definition
| they are directly proportional |
|
|
Term
| if we double enzyme concentration, what happens to max velocity |
|
Definition
|
|
Term
| if we half enzyme concentration, what happens to max velocity |
|
Definition
|
|
Term
| what does first order mean |
|
Definition
| when [S] < km, velocity is proportional to the substrate concentration and first order describes the rate |
|
|
Term
| what does zero order mean |
|
Definition
| when [S] > km, velocity is approx constant and equal to max velocity and independent of [S] making it zero order in respect to the substrate |
|
|
Term
| what is a lineweaver burk plot |
|
Definition
| inverse of michaelis menten |
|
|
Term
| what are the axis of a lineweaver burk plot |
|
Definition
|
|
Term
| what is the shape of a lineweaver burk plot |
|
Definition
|
|
Term
| what can we directly determinie from a lineweaver burk plot |
|
Definition
|
|
Term
| why do we need the lineweaver burk plot |
|
Definition
| because of the parabolic nature of the michaiels menten plot, Vmax is difficult to percisley determine |
|
|
Term
| what is the X axis on a lineweaver burk plot |
|
Definition
|
|
Term
| what is the y axis on a lineweaver burk plot |
|
Definition
|
|
Term
| in addition of Km and Vmax, what is a lineweaver burk plot useful for |
|
Definition
| determining mechanisms of action of enzyme inhibitors |
|
|
Term
| what happens in Km or Vmax increases to a linweaver burk plot |
|
Definition
|
|
Term
| what happens in Km or Vmax decreases to a linweaver burk plot |
|
Definition
| they will get further from 0 |
|
|
Term
|
Definition
| any substance that can diminish the velocity of an enzyme catalyzed reaction |
|
|
Term
| what does an irreversible inhibitor do |
|
Definition
| binds to enzymes through covalent bonds irreversibly |
|
|
Term
| what does a reversible inhibitor do |
|
Definition
| usually binds with non-covalent bonds and possibly covalent as long as the enzyme can be recovered |
|
|
Term
| what are the two types of reversible inhibitors |
|
Definition
| competitive and noncompetitive |
|
|
Term
| what does a competitive inhibitor do |
|
Definition
| binds reversibly to the same site that the substrate would normally occupy |
|
|
Term
| how does a competitive inhibitor affect Vmax, why |
|
Definition
| the effect of a competitive inhibitor can be overcome with lots of substrate so it does not affect Vmax because we assume there is unlimited substrate |
|
|
Term
| how does a competitive inhibitor affect Km, why |
|
Definition
| it increases the Km because most substrate is needed to achieve 1/2Vmax so the apparent affinity is lower |
|
|
Term
| on the graph for competitive inhibitors, what happens to the 1/Vmax point |
|
Definition
|
|
Term
| on the graph for competitive inhibitors, what happens to the -1/Km point |
|
Definition
| it becomes more negative (closer to zero) |
|
|
Term
| what is an example of a competitive inhibitor |
|
Definition
|
|
Term
| explain how statin drugs do competitive inhibition, what is the biological significance |
|
Definition
| statin is a structural analog to HMG CoA reductase which is involved in cholesterol synthesis so it competes for its active site, lowering cholesterol |
|
|
Term
| how does a noncompetitive inhibitor work |
|
Definition
| inhibitor binds reversibly to a site other than the substrate binding site, it can bind wether the substrate is bound or not |
|
|
Term
| how do noncompetitive inhibitors affect Vmax, why |
|
Definition
| they cannot be overcome by increasing substrate so they lower the Vmax |
|
|
Term
| how do noncompetitive inhibitors affect Km |
|
Definition
| they do not interfere with the binding of the substrate so it does not change the affinity, no affect |
|
|
Term
| what happens to the point -1/km on the graph due to a noncompetitive inhibitor |
|
Definition
|
|
Term
| what happens to the point 1/Vmax on the graph due to a noncompetitive inhibitor |
|
Definition
| it increases in Y value, it gets further from zero |
|
|
Term
| what is an example of a noncompetitive inhibitor |
|
Definition
|
|
Term
| explain how ferrochelatase does noncompetitive inhibition |
|
Definition
| it inserts Fe into the protophoryin which makes heme, fe noncompetitivly inhibits ferrocheletase by binding its sulfhydril groups on cystine stopping Fe getting into heme |
|
|
Term
| why is the rate of enzymes in the body affected by the concentration of the substrate |
|
Definition
| because physiological substrate is near the range of Km so an increase will prompt proportional increase in rate and vice verse. |
|
|
Term
| how a allosteric enzymes regulated |
|
Definition
|
|
Term
|
Definition
| they bind to sites other than the active site on enzymes altering their affinity to substrate (affect Km) or the catalytic activity (Vmax) or both |
|
|
Term
| what is a negative effector do |
|
Definition
| inhibit allosteric enzyme activity, decrease Vmax or increase Km |
|
|
Term
| what does a positive effector do |
|
Definition
| increase allosteric enzyme activity, increase Vmax or decrease km |
|
|
Term
| what is a homotrophic effector |
|
Definition
| when the substrate itself serves as an effector, most often positivly. alters the other binding sites of the enzyme changing their Km or Vmax |
|
|
Term
| what is another name for homotrophic effectrs actions |
|
Definition
|
|
Term
| what type of curve demonstrates cooperitivity |
|
Definition
|
|
Term
| what is an example of coopertivity |
|
Definition
|
|
Term
| what is a heterotrphic effector |
|
Definition
| effector is different than the substrate, possibly a product inhibiting the rate limiting step, binding the enzyme at a site other than the active site |
|
|
Term
| what is an example of a heterotrphic effector |
|
Definition
| PFK-1 is the rate limiting step in glycolysis, citrate from the TCA cycle can shut this step down if it builds up making the sythesis of glycogen vs glucose |
|
|
Term
| what is the most common form of enzyme regulation |
|
Definition
| covalent modification usually via phosphorlyation or dephosphorlyzation of the SER, ThR, or TYR -OH group |
|
|
Term
|
Definition
|
|
Term
| what does a phosphatase do |
|
Definition
|
|
Term
| what does fasting cause in metabolic enzymes |
|
Definition
| activates phosphorlyating kinases, activates catabolism and inhibiting anabolism |
|
|
Term
| what does a well fed state do to metabolic enzymes |
|
Definition
| inhibits phosphorylzation, deophsphorlyzation activated. activates anabolism and inhibiting catabolism |
|
|
Term
| explain how induction or repression can control enzymes |
|
Definition
| you can alter their synthesis by controling their gene expression or their degredation by controling other genes |
|
|
Term
| what qualifies an enzyme to be regulated by induction or repression of expression |
|
Definition
| it usually needs to be under specific physiological conditions and not in constant use |
|
|
Term
| how long does it take for gene alteration to control enzymes |
|
Definition
|
|
Term
| how long does it take for covalent measures to change enzyme activity |
|
Definition
|
|
Term
| why are steroids not immediatly effective |
|
Definition
| because they control gene expression not covalent modifications to enzymes |
|
|
Term
| describe the normal enzyme component of the blood |
|
Definition
| there are a small amount for things like coagulation and a teeny bit because of cell lysis and turn over |
|
|
Term
| why is having some enzymes from cell lysis and turn over in the blood ok |
|
Definition
| because they are normally removed |
|
|
Term
| when is having some enzymes from cell lysis and turn over in the blood a problem, what does this cause, what is it caused by |
|
Definition
| when they are not removed and build up, tissue damage, disease |
|
|
Term
| how can you determine the extent of tissue damage using plasma and where it came from |
|
Definition
| count the levels of enzymes from lysed cells, cells have specific enzymes so can you look at the type to see where they lysed from |
|
|
Term
|
Definition
| caralyze the same reaction but are a different on the amino acid level, they may also have different quatrentary subunits |
|
|
Term
| how can you find isoenzymes vs enzymes in the lab |
|
Definition
| electrophoreses, different amino acids give different weights |
|
|
Term
| why are isoenzymes useful |
|
Definition
| different organs have specific ones and can indicate the location of disease |
|
|
Term
| What type of effector is a homotroohic effector |
|
Definition
|
|
Term
| How does a homotroohic effector work |
|
Definition
| Substrate itself is the effector |
|
|
Term
| What does a homotroohic effector do to Vmax and Km |
|
Definition
| Increases Vmax and decreases Km of other substrate binding sites |
|
|
Term
| What is the shape of a curve for homotroohic effectors |
|
Definition
| Sigmoidal when Vo vs substrate concentration |
|
|
Term
| What type of effector shows cooperatively |
|
Definition
|
|
Term
| How does a heterotrophic effector work |
|
Definition
| Effector is different than the substrate |
|
|
Term
| Is a heterotrophic effector positive or negative |
|
Definition
|
|
Term
| What does heterotrophic effectors show is going on in the reaction |
|
Definition
|
|
Term
| What is feedback inhibition |
|
Definition
| Accumulation of product inhibits rate limiting step at a location other than a binding site for the substrate |
|
|
Term
| What is an example of feedback inhibition |
|
Definition
| PFK-1 is rate limiting step in glycolysis, citrate from the CAC can inhibit this step changing from production of glucose to glycogen |
|
|
Term
| How is covalent modification of enzymes done |
|
Definition
| Phosphorlyation or desphosphorlyation of -OH of ser, the, and tyr |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Does phosphorylation turn on or off genes |
|
Definition
| Either depending on the situation |
|
|
Term
| When fasting what enzyme is being inhibited, what enzyme is activated |
|
Definition
| Anabolic pathways were inhibited, kinases activated |
|
|
Term
| When well fed what pathway is inhibited, what enzyme is activated |
|
Definition
| Catabolism is inhibited, desphosphorlyation enzymes are activated |
|
|
Term
| What are ways other than phosphorylation we can regulate enzymes |
|
Definition
| Control transcription, control mRNA, altering gene expression (control synthesis or degration), |
|
|
Term
| What limits when we. An alter gene expression to control enzymes |
|
Definition
| You cannot do it for enzymes that are used all the time to make energy |
|
|
Term
| Way is the difference between the timing of covalent and genetic alterations to enzymes |
|
Definition
| Covalent takes minutes, genetics take hours |
|
|
Term
| What are the reasons enzymes are in the blood |
|
Definition
| Fragments due to cell lysis, normal blood enzymes like for clotting |
|
|
Term
| Why are the enzymes due to cell lysis in the blood medically significant |
|
Definition
| Normally the enzymes are removed so an increase in level can indicate tissue damage in the tissue that enzyme correlates to |
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Term
|
Definition
| Enzyme that catalyzes the same reaction but uses different amino acids to do it and may have a different quaternary structure |
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Term
| How can you identify isoenzymes from other enzymes |
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Definition
| If you do electrophoresis they will be a different weight due to their difference in size t the enzyme they are like |
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Term
|
Definition
| A prosthetic group tightly bound to a protein |
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|
Term
| What is a prosthetic group |
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Definition
| Coenzyme permeability associated with the enzyme or another protein and is returned to original form |
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|
Term
| What does heme do in cytochromes |
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Definition
| Electron carrier function, lots in ETC |
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|
Term
| What does heme do in catalyase |
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Definition
| Proximal enzyme. Breaks down hydrogen peroxide to water and oxygen |
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Term
| What is the shape of a heme called |
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Definition
|
|
Term
| What a thte bonds in the iron of heme bound to |
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Definition
| 4 nitrogens bind to iron, 1 to hb or myoglobin on r group of HIs of globin, binds oxygen |
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Term
| Where is myoglobin found in the body |
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Definition
| Cardiac and skeletal muscle |
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Term
| What is the function of myoglobin |
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Definition
| Binds oxygen very tight, only releases oxygen if the body is very low in it, it's high affinity can change the rate of diffusion in the cell |
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|
Term
| Describe the structure of myoglobin |
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Definition
| One chain similar to aha or beta, interior non polar site with his that binds 1 oxygen and a his that binds iron of heme, polar amino acids on surface |
|
|
Term
|
Definition
|
|
Term
| how many oxygen does a hemoglobin transport |
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Definition
|
|
Term
| how many oxygen does a myoglobin transport |
|
Definition
|
|
Term
| what kinds of molecules can a hemoglobin transport |
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Definition
| oxygen, CO2, H+, 23-BPG, bicarbonate |
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|
Term
| what mechanism regulates the oxygen binding site on heme |
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Definition
|
|
Term
| describe the quaternary structure of hemoglobin |
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Definition
|
|
Term
| what is the state of the hemoglobin in the T form |
|
Definition
| deoxygenated, lower oxygen affinity, rigid |
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|
Term
| dscribe the bonds of a hemoglobin in the T form |
|
Definition
| strong hydrophobic bonds between the alpha and beta chains. weak ionic and hydrogen bonds between the two alpga beta dimers |
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|
Term
| what is the state of hemoglobin in the R form |
|
Definition
| oxygenated, high oxygen affinity, relaxed |
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|
Term
| describe the bonds of a hemoglobin in the R form |
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Definition
| the bonds within the dimers will be the same but the ionic and hydrogen ones between the dimers will lessen |
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Term
| when looking at a hemoglobin curve, what location in the body does the left side indicate |
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Definition
|
|
Term
| when looking at a hemoglobin curve, what location in the body does the right side indicate |
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Definition
|
|
Term
| what is the shape of a hemoglobin curve |
|
Definition
|
|
Term
| what is the shape of a myoglobin curve |
|
Definition
|
|
Term
| what are the axis on a hemoglobin coopertivity graph |
|
Definition
| partial pressure of o2 (mmHg) vs degree of saturation of O2 |
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Term
|
Definition
| partial pressure of oxygen to achieve half the saturation in the atmosphere |
|
|
Term
| what does a low P50 indicate |
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Definition
|
|
Term
| what does a high P50 indicate |
|
Definition
|
|
Term
| in general, what does it mean if a Hb curve is shifted left |
|
Definition
| binds oxygen with higher affinity |
|
|
Term
| in general, what does it mean if a Hb curve is shifted right |
|
Definition
| more oxygen is released, less is bound to Hb. less degree of saturation in the lungs |
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|
Term
| what shift of a Hb curve is generally more benificial |
|
Definition
|
|
Term
| myoglibin P50 is usually _____. why? |
|
Definition
| low, because of the higher affinity it has for oxygen |
|
|
Term
| what are two important examples of cooperative biniding |
|
Definition
| hemoglobin and allosteric enzymes |
|
|
Term
| what is the heme-heme interaction |
|
Definition
| interaction on one site of Hb makes other sites increase their affinity for Hb allowing more oxygen to be delivered to the tissues in response to small changes in pO2 |
|
|
Term
| what does the pO2 in the tissues allow |
|
Definition
|
|
Term
| what does the pO2 in the lungs allow |
|
Definition
|
|
Term
|
Definition
| Hb has less affinity for oxygen at lower pH values shifting the curve right, unloading more oxygen. a greater pO2 is needed to achieve the same oxygen saturation |
|
|
Term
| what can cause lower blood pH and this the bohr effect |
|
Definition
|
|
Term
| what activity of Hb is favored at a low pH |
|
Definition
|
|
Term
| what activity of Hb is favored at high pH |
|
Definition
|
|
Term
| what is the bicarbonate reaction |
|
Definition
| CO2 + H2O -> H2CO3 -> HCO3 + H+ |
|
|
Term
| why does the Hb assume the T state without oxygen |
|
Definition
| because the pKa of his shifts without O2 so it cannot bind proteins as well, this stabilizes the T state leading to less oxygen affinity |
|
|
Term
| when in the T state, which way is the curve shifted |
|
Definition
|
|
Term
| how and where is 2,3-BPG made |
|
Definition
| product of glycolysis in RBC |
|
|
Term
| what does 2,3-BPG bind do |
|
Definition
|
|
Term
| what function does 2,3-BPG play |
|
Definition
| stabilizes the T form of Hb, decreasing oxygen affinity |
|
|
Term
|
Definition
| at picket between B globin chains to positive amino acids because they are negative |
|
|
Term
| what happens to 2,3-BPG when oxygen binds a Hb |
|
Definition
| it is expelled from the Hb |
|
|
Term
| what does 2,3-BPG do to the Hb curve |
|
Definition
|
|
Term
| what action does 2,3-Bpg help the Hb do |
|
Definition
| unload oxygen into tissues |
|
|
Term
| what diseases can cause the body to make more 2,3-BPG |
|
Definition
| chronic hypoxia, COPD, emphysima, high altitudes, anemia, hypoxia |
|
|
Term
| what do lung function decreasing diseases do to 2,3-BPG and the Hb curve |
|
Definition
| cause the body to make more of it, shifting it right |
|
|
Term
| when someone gets a blood transfusion, why for ~6 hours do they have problems letting their O2 go into the tissues |
|
Definition
| the transfused blood had the 2,3-BPG mostly deteroirate, after about 6 hours it builds back up. initially, the transfused blood will not release oxygen well |
|
|
Term
| what does the curve look like when someone has just had a blood transfusion, does it shift? |
|
Definition
| it is more like myoglobin, it is only slightly sigmoidal, shifts left |
|
|
Term
|
Definition
| it travels in the form of bicarbonate and when attached is a carbamate on the N terminal of AA of Hb turning the Hb into carbaminohemoglobin |
|
|
Term
| what is the equation for CO2 Hb interaction |
|
Definition
| Hb-NH2 + CO2 -> Hb-NH-COO` + H+ |
|
|
Term
| what effect does CO2 have on the structure of Hb |
|
Definition
|
|
Term
| what does CO2 do to the Hb curve |
|
Definition
|
|
Term
| what does CO2 do to the Hb affinity |
|
Definition
|
|
Term
| what does Hb have a higher affinity for: O2, CO2, 2,3-BPG, or CO |
|
Definition
|
|
Term
|
Definition
| at the oxygen binding site |
|
|
Term
| when CO attaches to Hb what physical changes does it cause |
|
Definition
| Hb goes into the R state, now has a higher affinity for oxygen or CO, whatever, less unloading |
|
|
Term
| what does CO do to the Hb curve |
|
Definition
|
|
Term
| describe the structure of fetal Hb, what does this cause |
|
Definition
| gamma chains lack some of the AA that interact with 2,3-BPG so low affinity for it provides a higher oxygen affinity allowing baby to steal O2 from mom |
|
|
Term
| what is the function of HbA2 |
|
Definition
|
|
Term
| what is another name for HbA1c |
|
Definition
| modified adult hemoglobin |
|
|
Term
|
Definition
| over time, adult Hb is glycosylated non enzymatically to an extent in proportion to the sugar around the RBC in their 120d |
|
|
Term
|
Definition
| it someone has been following their diabetes diet or it it isnt working |
|
|
Term
| what percent of Hb is FHb, HbA2, and HbA1c in an adult |
|
Definition
|
|
Term
| what is the most common inherited blood disorder |
|
Definition
|
|
Term
| when do the symptoms for sickle cell appear, why |
|
Definition
| around 6 mo old because the issue is with beta globin and you dont replace gamme globin with beta until then |
|
|
Term
| what are the symptoms of sickle cell |
|
Definition
| apisodes or crises (pain), chronic hemolytic anemia, increased susceptability to infection |
|
|
Term
| how long does a sickle cell live |
|
Definition
|
|
Term
| what is the exact mutation inoved in sickel cell, mutated to what |
|
Definition
| glutamate is replaced with valing going from negative to neutral |
|
|
Term
| how can you seperate sickle cell Hb and normal |
|
Definition
| electrophoresis because they are different weights |
|
|
Term
| what does the chance in amino acid in sickle cell cause structurarly |
|
Definition
| makes a pocket in b globin so it can bind to another Hb making Hb fibrils causing the cell to sickle only when the cell is deoxygenated |
|
|
Term
| why do sickled cells cause problems |
|
Definition
| they dont flow normally and stick to eachother and the walls, they cannot pass through small capilaries due to their rigidity |
|
|
Term
|
Definition
| pain from trying to smoosh sickle cells through capillaries |
|
|
Term
| what can increase severity of sickling in sickle cell anemia |
|
Definition
| anything that puts Hb in the deoxy state: high altitudes, flying in a non-pressurized plane, increasing CO2, decreasing pH, increasing 2,3-BPG |
|
|
Term
| what does dehydration do to someone with sickle cell |
|
Definition
| decreases blood flow causing less movement of oxygen and more Hb unloading, more Hb will be in deoxy form increasing sickling |
|
|
Term
| what can exercise to do someone with sickle cell |
|
Definition
| decreases pH / CO2 and causes more sickling |
|
|
Term
| what are some treatments for sickle cell |
|
Definition
| hydration, analgesic, antibiotic therapy, blood transfusion, hydroxyurea |
|
|
Term
|
Definition
|
|
Term
| what mutation happens in Hb C disease |
|
Definition
| lysine is substituted for glutamate (in the same spot as sickle cell) |
|
|
Term
| what are the symptoms of homozygous HbC disease |
|
Definition
| mild chronic hemolytic anemia, no infractive crises, no specific therapy |
|
|
Term
| what mutation happens in Hb SC disease |
|
Definition
| patient inherits one copy of HbS and one of HBC |
|
|
Term
| what are the symptoms of Hb SC disease |
|
Definition
| symptoms are more variable and between severe sickle cell and HbC disease. less frequent sickling leading to less frequent and severe crisis |
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