Term
|
Definition
-father of wave mechanics
-said chromosomes must have a "hereditary code-script"
-in other words they are bearers of information |
|
|
Term
| Griffith's transformation (1928) |
|
Definition
first evidence that cells contained discrete hereditary material that could genetically transform other cells
-R can not mutate to S |
|
|
Term
| Avery, Macleod & MacCarty (1944) |
|
Definition
-the transforming substance is DNA
-treated heat-killed S strain samples with different enzymes and the only one that did not transform was the DNase sample |
|
|
Term
| Hershey & Chase (1952) - confirmed AMM |
|
Definition
-distinguised b/w proteins and DNA as transforming principle
-radioactively labed bacteriophage with sulfur and phosphorus
-one labeled with phosphorus was the only one that showed up in the next gen of bacteriophage (DNA is def the transforming principle) |
|
|
Term
| genetic material must be capable of... |
|
Definition
1. replication
2. storage
3. expression
4. variation (mutation) |
|
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Term
|
Definition
|
|
Term
| Watson/Crick (1953) - base composition |
|
Definition
-proposed double helix based on Erwin Chargaff --> proposed that double straded DNA consists of ~50% purines (A/G) and ~50% pyrimidines (T/C)
- A=T and G=C
-%GC varies for organism to organisms |
|
|
Term
| Watson/Crick (1953) - x-ray diffraction |
|
Definition
| -rosalind franklin and maurice wilkins used x-ray diffraction to prove DNA was a double helix |
|
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Term
|
Definition
-talks about seeing DNA model for the 1st time
-became a pioneer in genomics and genetics
-developed the roundworm as a model organism (C. elegans) |
|
|
Term
| what is a nucleotide composed of? |
|
Definition
| a sugar, a phosphate, and a base |
|
|
Term
| Is DNA anti-parallel or parallel? What direction does it run? |
|
Definition
| DNA is anti parallel and runs in a 5' to 3'; direction. |
|
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Term
| Where is DNA located in the cell? Where are proteins made? |
|
Definition
| DNA is located in the nucleus and proteins are made in the cytoplasm. |
|
|
Term
| How many pairs of chromosomes do we have? How is DNA packed into these chromosomes? |
|
Definition
| We have 23 pairs of chromsomes and DNA is tightly packed into these chromosomes. |
|
|
Term
| Who is Gamow and what did he discover about proteins and translation? |
|
Definition
| He is the father of the Big Bang Theory and discovered that there are 64 triplets which leaves 20 distinct codons. |
|
|
Term
| What did Paul Zamecnik discover? |
|
Definition
| Protein synthesis does not take place in the nucleus. |
|
|
Term
| Why not an overlapping code? |
|
Definition
-greater info density
-puts constraint on sequence of amino acids in evry protein
-if it were overlapping, single nucleotide change would equal changing 3 codons and protein data showed single amino acid replacements (Brenner ruled out overlapping codes by analyzing protein fragments) |
|
|
Term
| Crick's adaptor hypothesis |
|
Definition
| There is an adaptor molecule, a unique one for each amino acid that take amino acids to the site of protein synthesis (called tRNA, there are 20) |
|
|
Term
| Brenner and Crick, 1961: a triplet code |
|
Definition
| -using chemical mutage proflavin, they inserted or deleted a single base pair |
|
|
Term
|
Definition
Dna to Rna to Protein
-by Francis Crick |
|
|
Term
|
Definition
-studied inborn errors of metablism
-alkaptonuria (dark urine, build up of homogentisic acid)
-maybe bacterial infection of the intestine
-autosomal recessive disease |
|
|
Term
| Who discovered Rh Blood Group? |
|
Definition
| discovered in 1940 by Karl Landsteiner and Alexander Wiener |
|
|
Term
| What are the Rh genes controlled by? |
|
Definition
| controlled by 2 closely linked and highly ypolymorphic genes that rearrange to produce 49 diff protein antigens |
|
|
Term
| What are the genotypes of Rh+ and Rh-? |
|
Definition
Rh+ = DD, Dd
Rh- = dd
(15% of caucasions, 8% of AA, and 1% of Asians are Rh-) |
|
|
Term
|
Definition
| hemolytic disease of the newborn aka Erythroblastosis fetalis |
|
|
Term
|
Definition
| incompatibility of the Rh blood group b/w mother and fetus .. mother is Rh- and baby is Rh+ |
|
|
Term
| What kind of trait (dominant/recessive) is Rh+? |
|
Definition
|
|
Term
| What do Rh- individuals lack? |
|
Definition
| They lack the Rh D antigen. |
|
|
Term
| What are the universal donor and receipient? |
|
Definition
Universal donor = O-
universal recepient = AB+ |
|
|
Term
|
Definition
| withdrawing amniotic fluid from Rh- pregnant woman |
|
|
Term
| What did Dr. Devis measure and how does it relate to maternal/fetus blood? |
|
Definition
| He measured bilirubin levels (yellow breakdown product of heme that is elevated for certain diseases. Bilirubin levels correlate with an exent to which fetal lood was being destoryed by maternal antibodies |
|
|
Term
|
Definition
| it is an anti-Rh or anti-D immunoglobulin, which blocks sensitization of mother after 1st pregnancy. |
|
|
Term
| What is Rho(D) immune globulin? |
|
Definition
| IgG anti-D (anti-RhD) antibodies that bind to, and lead to the destruction of fetal Rh D positive red blood cells that have passed from the fetal circulation to the maternal circulation. |
|
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Term
|
Definition
Identified by Murray Barr in 1949
-females have one, males do not.
-Barr bodies = inactive X (Xi) chromosomes |
|
|
Term
| Once the decision is made to deactivate an X chromosome, it is permanent, with the excpetion of the female germ cells (oocytes), which reactivate the inactive X. |
|
Definition
|
|
Term
| Transcription is deregulated in active X Chromosomes. |
|
Definition
| False. Transcription is upregulated in active X chromosomes. |
|
|
Term
| How does X inactivation work? |
|
Definition
-DNA bases are methylated
-Histones are modified.
-These changes cause inacive X to condense into a compact, darkly staining body: Barr Body |
|
|
Term
| The X inactivation center includes the XIST gene. What does this gene encode? |
|
Definition
|
|
Term
| When was prenatal diagnosis started and when did the first termination of an affected fetus happen? |
|
Definition
1955- sex of fetus could be determined
1960- 1st termination (hemophilia) |
|
|
Term
| What did the Roe v Wade (1973) case make legal? |
|
Definition
|
|
Term
|
Definition
| the chromosome complement of any given cell. |
|
|
Term
| What did Jerome Lejeune discover? |
|
Definition
| He discovered that Down syndrome is caused by an extra copy of chromsome 21 (trisomy 21) |
|
|
Term
|
Definition
| a hollow needle is instered through the mother's abdomen into the uterus and amniotic fluid is drawn for analysis |
|
|
Term
|
Definition
When chromosomes don't come apart
-failure of paired chromosomes to disjoin (separate) during cell dviision so that both chromosomes go to one daughter cell and none to the other. |
|
|
Term
| Chorionic Villus Sampling |
|
Definition
-more difficult that amniocentesis
-fetal chromosomes karyotyped from chorionic villi @ 11-14 weeks (PND in 1st trimester) |
|
|
Term
| Screening in Practice: B-Thalassemia |
|
Definition
-caused by mutations in NBB gene
-this is a disease of the RBC
-heterozygotes are reasonably healthy
-more prevalent where malaria is
-babies w/ this disease do not make adult hemoglobin (appear normal at birth)
-during 1st year of life: facial deformities, lack of growth, fatigue, shortness of breath, jaundice |
|
|
Term
|
Definition
-1 in 7 carried an HBB mutation
-screening program aimed @ unmarried couples, prenatal diagnosis available
-church approved and required certificates that showed marrying couples have undergone screening and counseling
-very few affected children born these days |
|
|
Term
| what is a restriction enzyme? |
|
Definition
they cut DNA at specific nucleotide sites
-cuts both places on either strand |
|
|
Term
|
Definition
they are used to follow inheritance of pieces of DNA through famililes
- |
|
|
Term
| What did Frederick Sanger and Gilbert figure out? |
|
Definition
How to sequence DNA
sanger= enzymatic sequencing
gilbert = chemical sequencing
-they shared nobel prize in 1980 |
|
|
Term
| What is the difference b/w dNTP and ddNTP |
|
Definition
ddNTP = something tha tinterrupts DNA polymerase
dNTP = just a base pair |
|
|
Term
| How does sanger sequencing work? |
|
Definition
1. DNA is heated to separate the 2 strands.
2. A primer is annealed to one of the separated template strands.
3. 4 tubes: G, A, T, C; dNTPs, ddNTPS at 1:300, and enzyme |
|
|
Term
| What does the G tube include? |
|
Definition
| all four dNTP's, ddGTP and DNA polymerase |
|
|
Term
| Reading the Sanger Termination Sequence |
|
Definition
1. Load four tubes into the gel.
2. Read from bottom to top because shortest chain is on the bottom. |
|
|
Term
| What is PCR and who invented it? |
|
Definition
-Kary Mullis invented it in 1983.
-the goal of it is to created a billion copies of a piece of DNA of interest |
|
|
Term
| What is the difference between a genetic map and a physical map and which was published first? |
|
Definition
| Genetic maps were published first and it has an indirect estimate of the distance b/w 2 markers. Physical maps have a direct estimate of the amount of DNA b/w 2 markers. (old school=cytogenetic maps, today= sequence maps w/ every base pair) |
|
|
Term
|
Definition
| the closer two genes are, the more likely they are to be inherited together. |
|
|
Term
| When did the race to sequence the human genome begin? |
|
Definition
|
|
Term
| What type of mapping did the HGP rely on? |
|
Definition
|
|
Term
| What is venter shotgun sequencing? |
|
Definition
| the method used to complete the private genome project |
|
|
Term
| How much of the genome encodes protein? |
|
Definition
|
|
Term
| How many genes are there in the human genome? |
|
Definition
|
|
Term
| What do non protein coding sequences encode? |
|
Definition
| They encode non coding RNAs that play key roles in gene regulation. |
|
|
Term
|
Definition
small insertions or deletions
-can be coding or non-coding |
|
|
Term
| What are microsatelites/short tandem repeats? |
|
Definition
repeat of 2,3,4 or more NTs
-they are highly polymorphic (error during replication-->slippage) |
|
|
Term
|
Definition
RNA intermediate that jump around genome
-it is a runaway process in our genome where there is selection pressure controlling where these sequences jump about |
|
|
Term
|
Definition
| non random association of alleles in haplotypes in the population |
|
|
Term
|
Definition
-the mutation process
-drift
-incompatibility
-different alleles in diff populations |
|
|
Term
|
Definition
|
|
Term
| African populations and LD |
|
Definition
| African populations demographically old and have a lot less linkage disequilibrium than populations outside of Africa |
|
|
Term
| Haw many rare variants are in the human genome? |
|
Definition
| probably close to 3 million. |
|
|
Term
|
Definition
-looked a wild fly populations to see what happens to genetic variation in a natural pop of flies
-said that through mutations in genes that natural selection takes place |
|
|
Term
|
Definition
-found that mutations can be induced by x-rays
-studied mutations in flies in lab, mostly ones generated by mutations. |
|
|
Term
| What is the classical theory of thought and who supported this? |
|
Definition
-Mueller supported it
-assumes that @ every loucs every individual is homozygous for a "wild-type" gene.
-each indiv is het for rare deleterious alleles at a handful of loci for hundreds to thousands of genes |
|
|
Term
| what is the balanced theory and who supported it? |
|
Definition
-Dobzhansky supported it
-indivs are het @ nearly every one of their loci, and only rarely will a locus be homozygous (exception: offspring of closely related parents)
-no allele can properly be termed "wild-type" since normal indivs are het |
|
|
Term
| How do we know common diseases are heritable? |
|
Definition
| there is a correlation among relatives in terms of what diseases they get. |
|
|
Term
| What is a single gene disease? |
|
Definition
| a genetic disease that results from a mutation at a single gene (Tay Sachs, cystic fibrosis) |
|
|
Term
| What is the common disease common variant hypothesis? |
|
Definition
-most variants in an INDIVIDUAL are common in the population
-variants that are relatively common in population are important for common disease |
|
|
Term
| How does LD relate to common variants? |
|
Definition
| If variants are associated with one another, we just have to look @ a subset of these variants |
|
|
Term
| What was the basic paradigm for studying common variation? |
|
Definition
|
|
Term
|
Definition
-a representative single nucleotide polymorphism (SNP) in a region of the genome with high linkage disequilibrium
-HapMap hopes to use them to identify genes responsible for certain disorders. |
|
|
Term
| What is a Manhattan plot? |
|
Definition
| association measure for each other 550,000 variants when u test it for how associated it is which who is cured |
|
|
Term
| What is a significant p-value for manhattan plot? |
|
Definition
|
|
Term
| How much does GWAS explain? |
|
Definition
| the data from GWAS explains very little of the genetic control that we think is there. |
|
|
Term
|
Definition
the proportion of the variation in the population that is due to genetic variation in the population.
-for height, heritability is 0.8. |
|
|
Term
| What is an example of rare variant that causes disease? |
|
Definition
|
|
Term
| What type of copy # variant is responsible for velo cardio facial syndrome? And what disease does this syndrome increase the risk of? |
|
Definition
|
|
Term
| True or false? Copy number variation is the ONLY type of genetic variation that can be seen on gene chips used for GWAS. |
|
Definition
|
|
Term
| How do things like HIV set point, warfarin dose, abacavir hypersensitivity, hepatitis C treatment response relate to GWAS studies? |
|
Definition
| They are all relatively new and selection does not mind and GWAS has found large effects of common variants on these traits. |
|
|
Term
| How do things like height, bipolar disease, hypterension schizophrenia, and diabetes relate to GWAS studies? |
|
Definition
| these traits are relatively old and GWAS has found nothing or relatively little (common variants only explain a little proportion of genetic cause) |
|
|
Term
|
Definition
| the missing explanation of heritability |
|
|
Term
| what are the possible explanations for missing heritability? |
|
Definition
| epigenetics, interactions/epistasis, rare variants |
|
|
Term
| What is epigenetics? What are some examples of them? |
|
Definition
-heritable changes that are not encoded in the DNA sequence
-modifications of histones
-methylation of DNA changes the packaging of the DNA as to influence the way genes are expressed |
|
|
Term
| Are genes more likely to be expressed if they are not methylated? |
|
Definition
|
|
Term
|
Definition
| the interaction of alleles at 2 different loci (genes) produces an unexpected phenotype given the individual effects of each allele. |
|
|
Term
|
Definition
| GWAS results showed that common variants or large effect do not exist for most traits. |
|
|
Term
|
Definition
| the data release policies for the HGP |
|
|
Term
| Why is epigenetics not reliable? |
|
Definition
| Because epigenetic modification is not stable across generations |
|
|
Term
| If epigenetics were stable.. |
|
Definition
| they would be in LD with SNPs and therefore produce strong GWAS signals |
|
|
Term
| What is the downfall of interactions in GWAS? |
|
Definition
-they are very difficult to test without prior hypothesis
-there may also be interactions that we never find. |
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|
