MCBG Exam 2 Flashcards
(120 cards)
1
Q
What is it called when you go from RNA–>protein?
A
Translation
2
Q
Three letter repeats which correspond to amino acids.
A
Codons.
3
Q
What are the three stop codons?
A
UAA, UAG, UGA
4
Q
What is wobble?
A
When the 5’ nucleotide of the anticodon can pair with multiple different nucleotides in the 3’ position of the codon.
5
Q
What are the 4 steps of translation?
A
- Charging of the tRNA.
- Initiation.
- Elongation.
- Termination.
6
Q
What are reading frames?
A
Reading frames are stretches of mRNA which are read in triplets and code for a specific amino acid sequence.
7
Q
Why are reading frames so important?
A
If the nucleotide sequence is not read in the correct reading frame then the wrong protein will be produced- could be nonfunctional or have a toxic effect.
8
Q
What is a tRNA?
A
An RNA molecule which folds in a specific way and is used to read the RNA code and add the amino acid which the RNA codes for to the growing polypeptide.
9
Q
What attaches amino acids to their tRNAs?
A
aminoacyl-tRNA synthetases.
10
Q
How do aminoacyl-tRNA synthetases check to make sure the correct amino acid is put on the correct tRNA?
A
- The anticodon is read to ensure it is the proper sequence for the amino acid-this can be less important in amino acids with very different nucleotide sequences for the same amino acid.
- The acceptor arm is also read to ensure a proper match.
- If the amino acid is too large, it will not fit properly in the enzyme and cannot add to the tRNA. If the amino acid is too small it will “flop” into the proofreading site and will be cleaved off of the tRNA. If the amino acid is the correct size, it will fit properly into the enzyme and will be added, but will be too large to fit into the proofreading site.
11
Q
What is the error rate of tRNA charging?
A
1 in 40000 amino acids.
12
Q
How do prokaryotic ribosomes know where to start translation?
A
The Shine-Delgarno sequence precedes the start codon and binds to the small subunit of the ribosome.
13
Q
What is the Shine-Delgarno sequence and what is its function?
A
The Shine-Delgarno sequence is a 3-9bp sequence in prokaryotic mRNA which is upstream of the start codon. This sequence binds to the 16SrRNA in the small subunit of the ribosome and this tells the ribosome where to begin translation.
14
Q
What is the function of the small ribosomal subunit?
A
To ensure correct pairing between the mRNAs codon and the tRNAs anticodon.
15
Q
What is the function of the large ribosomal subunit?
A
To catalyze and guide peptide bond formation.
16
Q
What is the first amino acid added in prokaryotic translation?
A
formylmethionine, a modified methionine.
17
Q
Describe the steps of eukaryotic translation initiation.
A
Step 1: eIF4 binds to the 5’ end of mRNA
Step 2: eIF4B stimulates the helicase activity of eIF4A
Step 3: The small subunit recognizes the eIF factors and binds to the mRNA.
Step 4: The small subunit and tRNA scans along the mRNA looking for the first start codon. Once a start codon is found, the GTP on eIF-2 is hydrolyzed and the eIFs dissociate.
Step 5: The large subunit binds to the small subunit (with the tRNA in the P site and translation can begin.
18
Q
How is eIF-2-GDP recycled?
A
Guanine nucleotide exchange factor eIF-2B binds to it and exchanges its GDP for a GTP.
19
Q
What are the 4 binding sites on the ribosome?
A
mRNA site, E site, P site and A site
20
Q
What are the bacterial elongation factors?
What are the eukaryotic elongation factors?
A
EF-Tu and EF-G
EF-1 and EF-2
21
Q
What does each elongation factor do?
A
EF-Tu-GTP binds to each tRNA as they enter the A site. The hydrolysis and exit of EF-Tu provide 2 short lags for an incorrect tRNA to exit the A site. This is what is partially responsible for the 99.9% accuracy of the ribosome.
EF-G-GTP binds near the A site. When its GTP is hydrolyzed it provides the energy to move the mRNA/tRNA complex along by one codon to the P and E sites.
22
Q
Describe the termination of translation.
A
When the ribosome reaches a stop codon termination factors bind and carry a single molecule of water into where the last amino acid is still attached to its tRNA. This molecule of water hydrolyzes the bond between aa and tRNA and the ribosome dissociates.
23
Q
What goes into the fidelity of protein synthesis?
A
(1) Aminoacyl tRNA synthetase must recognize the correct tRNA
(2) Aminoacyl tRNA synthetase must select the correct amino acid
(3) mRNA must be fully processed (in eukaryotes) prior to translation initiation
(4) The ribosome matches the mRNA codon to the tRNA anticodon.
The correct anticodon forms a stronger interaction with the codon than an
incorrect pairing.
(5) GTP hydrolysis and release of EF-Tu elongation factor provide short
delays allowing the tRNA to be released from the A-site of the ribosome
before an incorrect amino acid is irreversibly added into the peptide chain.
24
Q
What is a Svedberg unit?
A
A unit of density which corresponds to how far a molecule travels in a centrigugation experiment in a specif medium. The size of a protein in Svedberg units correlates to the size of the protein in mass.
25
What are the sizes of the bacterial ribosomal subunits? The size of the whole ribosome?
30S (small) and 50S (large). The whole ribosome is 70S.
26
What are the sizes of the eukaryotic ribosomal subunits? The size of the whole ribosome?
40S (small) and 60S (large). The whole ribosome is 80S.
27
What RNA is in the bacterial ribosome, and what subunit is each in?
16S RNA is in the small subunit, 5S and 23S are both in the large subunit.
28
What RNA is in the eukaryotic ribosome, and what subunit is each in?
18S RNA is in the small subunit. 5S, 5.8S and 28S RNAs are in the large subunit.
29
Explain the concept of molecular mimicry.
Creating a molecule which looks like a biologically active molecule in order to compete with that molecule, but not be biologically active (might bind what a molecule would bind but can't be catalyzed).
30
What are the components of creating a functional protein from a polypeptide chain?
Proper folding
Binding of cofactors
Covelant modifications
Associating with partner proteins
31
When does protein folding take place?
As the polypeptide is being synthesized. Or later with the help of a chaperone.
32
What is a chaperone? Give examples of 2 chaperones.
A chaperone is a protein which helps to ensure that a protein folds correctly.
hsp70- Interacts with exposed hydrophobic patches on proteins immediately after leaving the ribsome. ATP hydrolysis causes the hsp70 to bind tightly to the protein. Repeated binding and release help protein refold.
hsp60- Forms a barrel shaped structure to isolate misfolded proteins. This prevents their aggregation and provides a favorable environment for them to refold.
33
How are genes regulated? At what stage does each element of regulation occur?
Transcription:
chromatin structure
histone modification
transcription factors
ncRNAs
Translation:
splicing
ncRNAs
34
What is a gene unit?
A region of DNA which contains a gene and all of its regulatory elements.
35
What is an insulator?
Protein which bind sequences between gene units and prevent the machinery from one unit from interacting with the other.
36
What is the core promoter region?
-40 to +40 where 0 is the start site.
37
What is the proximal promoter region?
-200bp to +50bp where 0 is the start site.
38
What are regulatory elements?
Regulatory elements are short sequences of DNA that bind the transcription factors.
Each regulatory element may bind multiple transcription factors.
39
Where are regulatory elements located?
Regulatory elements can be located up to 50 kB from the start of transcription.
Regulatory elements can be placed upstream or downstream from start of transcription.
40
What is the SWI/SNF complex?
A chromatin remodeling complex.
41
How can histones be modified to change how dense/loose the DNA is?
Their N terminal tails can be acetylated, methylated or phosphorylated.
42
What are the main amino acid that is modified in the tail, and what modifications take place on it?
Lysine can be actylated or methylated (mono-, di- or tri-), lysine can also be phosphorylated.
43
What are chromodomain proteins?
Proteins which bind to methylated amino acids.
44
What are bromodomain proteins?
Proteins which bind to amino acids which are acetylated or phosphorylated.
45
What are some characteristics of reading and writing histone code?
Histones are modified in specific and sequential ways. This specific set of modifications is then read and bound by proteins which then carry out a specific function (ex: TFIID binds 2 acetylated lysines at the start of transcription).
46
What are some common transcription factor motifs?
1. Helix-turn-helix (HTH)
2. Helix-loop-helix (HLH)
3. Zn finger
4. bZIP
47
What are the 3 main domains of transcription factors?
DNA binding domain-binds a specific DNA sequence.
Dimerization domain-allows each TF to homo- or heterodimerize.
Activation domain-the business end of the protein.
48
What are the characteristics of a helix-turn-helix transcription factor?
An alpha helix which recognizes DNA sequences in the major groove.
A second alpha helix which stabilizes the first.
A dimerization domain, allowing 2 TFs to bind to the DNA.
49
What is a pseudopalindrome? What significance does one play in the binding of transcription factors?
Pseudopalindromes are sequences where a palindromic sequence is separated by several nucleotides. This spacing allows dimerized transcription factors to bind, which provides much greater specificity and affinity.
50
What are the characteristics of helix-loop-helix transcription factors?
* Dimer structure.
* Each monomer contains a recognition helix joined by a loop to a second helix which contains a leucine zipper motif.
* The recognition helices from each monomer bind to adjacent turns of the major groove (usually palindrome).
51
What are some examples of HTH transcription factors?
tryptophan repressor, lambda cro, lambda repressor fragment, CAP fragment
52
What are some examples of HLH transcription factors?
Myc, Max, Mad, and MyoD
53
What are the characteristics of a Zinc finger transcription factor?
Motif commonly characterized by a Zn atom coordinated by two Cys and two His (C2H2) or four Cys (C4) (can be any combination of Cys and His).
Intervening polypeptide chain of 12-14 amino acids present an a-helical segment and a b-strands segment.
a-Helix is a recognition helix that binds to DNA.
Typical transcription factor has multiple Zn finger motifs that bind in tandem to adjacent turns of the major groove of the DNA.
54
What does bZIP stand for? What are some characteristics of bZIP transcription factors?
bZIP stands for basic-leucine zipper.
Binds as homo- or hetero-dimer to DNA
Dimer forms a-helical scissor structure, each monomer is a long a-helix binding to a half-site of the palindromic element in the DNA.
DNA binding module contains multiple basic amino acids.
Dimerization is through leucine zipper (coiled-coil hydrophobic interaction).
55
What are some methods to analyze regulatory elements in gene expression?
Footprinting with DNAaseI for transcription factor binding sites.
Gel-mobility shift assay to show protein-DNA complexes.
Chromatin immunoprecipitation (CHIP assay).
Reporter genes to assay regulatory elements in specific cells.
56
What are the steps in a DNAase 1 footpront assay?
1. Random cleavage of DNA sequence of interest using DNAase 1.
2. Removal of the protein and separation of the DNA strands.
3. Separation of remaining DNA strands into size by gel electrophoresis.
Notes: You need to know the concentration of DNA that you will cleave and add only enough DNAase so that each DNAase molecule cleaves about 1 molecule of DNA (otherwise you will just get a lot of really small fragments instead of variable sized ones).
57
What are the steps in a gel mobility shift assay?
1. Have radioactively labeled DNA sequence of interest.
2. Take cell extracts from cells in question.
3. Incubate them together so the proteins that can bind to the DNA will bind.
4. Run on a gel to see what binds to the DNA (the larger the protein the slower it will move through the gel)
58
What are the steps for a ChIP assay?
1. Gather cells of interest.
2. Cross link DNA of these cells with formaldehyde.
3. Lyse cells.
4. Break DNA into small (~300bp) sizes.
5. Use antibody to the protein of interest to preferentially pull out protein-DNA complexes where the protein is bound.
6. Reverse cross linking (thus freeing the DNA).
7. Amplify the DNA gathered by PCR.
8. This DNA corresponds to the regions of the genome bound by this protein.
59
What are the elements of a reporter gene assay?
1. Identify and amplify regulatory region of a gene in question.
2. Insert region into a construct which is upstream of a reporter gene (luciferase or ß-gal).
3. Stick that bad boy into a cell culture (transformation/transfection). Or into embryos of model organism.
4. Wait.
5. See if reporter gene is expressed (how much in terms of cell culture and how much and where in terms of model organism).
60
What does combinatorial gene control mean? What significance does this have for developing a diverse population of cells within a single organism?
Combinatorial gene control means that multiple different regulatory proteins can bind to an identical regulatory element in a gene, and also that multiple different genes can be controlled by a single regulatory protein.
This has the effect of allowing a huge amount of diversity when it comes to turning on and off genes, meaning that an organism can create a massive amount of cell diversity from relatively few regulatory proteins and regulatory sequences, especially given that some combinations will activate and some combinations repress a gene’s expression.
61
What is a mediator complex?
A mediator complex is a complex of proteins which "reads" what regulatory proteins are bound to different regulatory elements of a gene and "transmits" the regulatory action of those proteins to the transcription machinery. This allows distal (far away) and disparate (spread out) elements to have an effect on gene expression.
62
What are Myc, Max, and Mad and what do they do?
They are transcription factors which dimerize. What dimerizations occur affects the expression of genes regulated by an E-box element. When Max dimerizes with Mad transcription is actively repressed. When Max homodimerizes, genes are expressed in small amounts (called "leaky" genes) and when Max dimerizes with Myc, the genes are expressed in large amounts.
63
What are some ways for a cell to send a signal which will affect gene expression?
1. Protein synthesis.
2. Ligand binding.
3. Protein phosphorylation.
4. Addition of second subunit.
5. Unmasking.
6. Stimulation of nuclear entry.
7. Release from membrane.
64
Why do cells in females inactivate one X chromosome?
Most gene expression is highly regulated and dose dependent. Having 2 fully functional X chromosomes would give females twice the concentration of the genes on the X than males, which would be toxic to the cells.
65
What does epigenetic mean?
Epigenetic refers to the inheritance or passage of information from parental cells to progeny cells by a mechanism other than that from the “instructions” within the sequence of nucleic acid bases of the copied DNA.
66
How does epigenetic regulation occur?
Epigenetic mechanisms occur through modification of either DNA or gene regulatory proteins.
67
What DNA sequences are methylated and where within the sequence does the methylation occur?
CpG sequences are preferentially methylated. This methylation occurs on the 5th carbon of the base of the cytosine.
68
How is methylation of DNA passed down from generation to generation?
Maintenance methylase methylates DNA strands at hemimethyl sites in newly synthesized DNA.
69
What does methylation of DNA do to gene expression?
Methylation completely silences gene expression (methylation prevents Polymerase binding and function and methylation recruits histone modification complexes and deacetylases.
70
How are histone modifications passed down from generation to generation?
Maintenance acetylases act to acetylate histone proteins of nucleosomes that are hemi-acetylated in newly formed progeny cells. Thus the same acetylated regions within the chromatin of a parental cell may be maintained in the progeny cell.
71
What is HDAC?
Histone deacetylase
72
What is HAT?
Histone acetyltransferase.
73
What is genetic imprinting?
Genetic imprinting is the passing down of specific genetic information in a non-Mendelian fashion through retention of methylation of a gene from one parent or the other.
74
What are some properties of genetic imprinting? How many genes are affected?
Usually, but not always, the hyper-methylated gene is not expressed while the hypo-methylated gene is expressed in offspring.
Imprinting is sex dependent, a particular gene retains its methylation in either the sperm or the egg but not both.
Imprinting due to DNA methylation of the regulatory element in a gene being retained through meiosis, when all methyl groups are removed from the great majority of the genes.
Leads to sex-dependent non-Mendelian genetic expression of the imprinted gene.
Genomic imprinting (retention of methylation) is known to occur in about 50 human genes.
75
Give a semi in depth list of ways eukaryotes regulate gene expression.
1. transcriptional control (transcript produced or not)
2. attenuation (rare) / riboswitches (transcript prematurely aborts, then is degraded)
3. RNA processing control
\*alternative splicing (different transcripts produced)\*- big one
capping / cleavage / polyadenylation (functionality of transcript/stability of transcript)
4. RNA editing (rare) (changes to the sequence/modifications)
5. nuclear export (rare) (exported vs degraded)
6. translation control
localization control (where is protein exported to in the cell)
translation initiation (polypeptide produced or not)
7. mRNA stability (degraded or not)
8. protein control
protein turnover (how long does it stay until it gets degraded)
protein modification/protein inhibition (protein activity level aka activation/inhibition)
76
Why is splicing so important for gene regulation?
It allows the cell to be able to generate a huge number of different proteins from one stretch of DNA.
Ex: DSCAM in drosophila- from 12 A exons, 48 B exons, 33 C exons and 2 D exons it can create 38000 unique splice variants...
77
How is splicing regulated?
Splicing is regulated through the binding of activator or repressor proteins to the splice site which regulates whether or not splicing occurs at that site.
78
79
What role does alternate splicing play in antibody production?
Alternate splicing/splicing regulation causes an additional transmembrane domain to be translated which causes the immunoglobulin molecule to be incorporated into the membrane. When splicing does occur, a stop codon is skipped over, causing the transmembrane protein to be transcribed. When splicing does not occur, the stop codon is read and the translation is terminated before the transmembrane domain.
80
How is translation regulated by eIF-2?
eIF-2 is an initiation factor required for translation initiation. eIF-2 binds to GTP, which activates the protein, and when this GTP is hydrolyzed to GDP eIF-2 is inactivated. The molecule responsible for regulating eIF-2 activity is eIF-2B, a guanine nucleotide exchange factor which replaces the GDP with a GTP thus reactivating eIF-2.
Also: if inactive eIF-2 is phosphorylated then it binds eIF-2B and sequesters it as an inactive complex, which dramatically slows new protein synthesis.
81
How is eIF-4E regulated?
The protein 4E-BP binds to and sequesters eIF-4E. Via signal transduction pathways, 4E-BP can be phosphorylated which makes it unable to bind to eIF-4E, freeing eIF-4E to be able to bind the cap and complex with eIF-4G and help assemble the ribosome.
82
What is an inefficient transcript?
A transcript which is normally not translated due to the presence of another factor such as eIF-4E. Usually this is due to an earlier start codon which would be masked in RNA folding if not for eIF-4E.
83
What are the two main ways to degrade mRNA?
Shortening of the poly-A tail (slow degredation) and decapping of the 5' end (fast degredation).
84
What is a miRNA?
miRNAs or microRNAs are short noncoding RNAs which form hairpins and then are cleaved by dicer and separated into single strands. These single strands are used to recognize specific mRNA transcripts and mark them for sequestration and/or degredation.
85
What is argonaut?
Argonaut is a protein in the RISC complex, when miRNAs in the RISC complex bind to an mRNA argonaut cleaved both the miRNA and mRNA.
86
How does miRNA complimentarity affect the RISC complexes activity against mRNA?
miRNA binding can differe depending on the number of complimentary bases it has to a sequence of mRNA. miRNAs have a 7nt seed sequence, which may loosely bind a number of different mRNAs. When just the seed sequence binds the complex sequesters the mRNA and it is slowly degraded. When the miRNA has a great deal of complimentarity to the mRNA the RISC complex cleaves the mRNA (rapid degradation)
87
What is nonsense mediated mRNA decay?
There are proteins which bind where an mRNA has been spliced. These are removed by the translation machinery. If the ribosome reaches a stop codon but there are still more of these proteins on later splice junctions, the mRNA is decapped and quickly degraded.
88
What is ubiquitination? What does ubiquitination do to a protein?
Ubiquitination is the process of putting a small molecule onto the lysines in a protein. This usually results in polyubiquitination (long ubiquitin chains). Polyubiquitination marks proteins for degredation by proteosomes.
89
Give a detailed account of the process of ubiquitination.
1. E1 (ubiquitin activating enzyme) puts a ubiquitin molecule onto E2 (ubiquitin conjugating enzyme).
2. E2 binds to the substrate with E3 (ubiquitin protein ligase).
3. E3 transfers the ubiquitin molecule from E2 to the protein (repeated for polyubiquitination).
4. The ubiquitin on the protein is recognized by a proteosome and the protein is degraded.
5. Free ubiquitin molecules are gathered by E1 so they can be recycled.
90
Why is it so important for cell cycle regulators to be highly regulated and degraded?
Improper timing of a cell cycle regulator could have devastating effects on cell division, so any abnormality is either dealt with through senecense or death.
91
What are some types of proteins regulated by ubiquitination?
* Cell cycle regulatory proteins
* Apoptotic regulatory proteins
* Transcription factors
* Components of signal transduction pathways
* Components of the mitotic machinery
* Abnormal or damaged cellular proteins
92
Name some diseases associated with mutations in the ubiquitination pathway and give details about them.
Parkinson’s disease
* Parkin, an E3 ubiquitin protein ligase
* α-Synuclein, a substrate for Parkin that can produce insoluble protein aggregates in selected regions of the brain
Hereditary tumors of the retina, brain, kidney and others tissues
•VHL (von Hippel-Lindau protein): a component of an E3 ligase complex that targets HIF, a transcription factor that promotes angiogenesis
Hereditary breast and ovarian cancer
•BRCA1 and BRCA2: components of an E3 ubiquitin ligase that activate proteins involved in DNA repair (a non-traditional role for ubiquitination)
Angelman syndrome
•UBE3A: deletion of this E3 ligase contributes to the mental retardation observed in Angelman syndrome
93
What percentage of pregnancies result in a live birth? What percentage spontaneously abort?
85% result in live birth, 15% spontaneously abort.
94
Of all pregnancies, what percentage have normal chromosomes? What percentage do not?
92% of all live births have normal chromosomes, 8% do not.
95
Of all pregnancies with abnormal chromosomes, what percentage are live births? what percentage are spontaneously aborted?
6.3% of all pregnancies with chromosomal abnormalities are live births, 92.7% of pregnancies with chromosomal abnormalities result in spontaneous abortion.
Note: most of the spontaneous abortions are from unbalanced abnormalities and aneuploidy.
96
What is the short arm of the chromosome referred to as in notation? The long arm?
The short arm is termed as the p arm and the long arm is the q arm.
97
What is a chromosomal satellite?
A small part of the chromosome which contains many repeats of the ribosomal components. Connected to the centromere by a stalk.
98
What does the term metacentric refer to?
When there is equal amounts of genetic material on the short and long arms of the chromosomes.
99
What does the term submetacentric mean?
When more genetic material is on the long arm of the chromosome.
100
What does the term acrocentric refer to?
Essentially when there is no genetic information (except for satellites) on the small arm of the chromosome.
101
What is an ideogram?
A representation of the G-banding pattern of the human chromosomes at metaphase.
102
Explain the chromosome band numbering system.
ex: 18p2.2
18 refers to the **chromosome number**
p refers to the **arm**
2 refers to the **region** (numbers start at the centromere)
the second 2 refers to the **band** in that region (numbers also start at the closest to the centromere).
note: when you geisma stain at prometaphase you can get higher resolution and can actually distinguish **sub-bands**
103
What are the properties of the bands seen with geisma staining?
Dark Staining (G-bands)
* Stain heavily with dyes that stain AT-rich regions.
* Maybe AT rich
* Condenses early during the cell cycle and replicates later
* Gene poor
* Alu poor but LINE rich
Pale bands (correspond to R bands)
* Stains weakly with Giemsa and Quinicrine
* Maybe GC-rich
* Condenses late during the cell cycle, but replicates early
* Gene rich
* LINE poor, but Alu rich
104
What are some alternative chromosome staining methods? What do they show?
* **Q-banding** - chromosomes are stained with quinacrine and examined by fluorescence microscopy. The fluorescent Q bands corresponds almost exactly to the G bands.
* **R-banding** – produced by Giemsa staining of chromosomes heated in phosphate buffer. Results in a dark and light banding pattern that is the reverse of that produced by Giemsa. R banding is the standard method for cytogenetic analyses in Europe and in some US labs.
* **Fluorescence R-banding** – untreated chromosomes are stained with acridine orange and examined by fluorescence microscopy. Fluorescent bands correspond to light bands obtained with Giemsa staining.
* **High resolution banding (prometaphase banding)** – G- or R- banding of chromosomes obtained at an early stage of mitosis (prophase or prometaphase) when they are less condensed.
105
What is the result of autosomal chromosome monosomies during pregnancy?
The offspring are not viable and die.
106
Unlike monosomies, trisomies are sometimes (but not usually) tolerated. What are the trisomies that can result in live birth, what are they called, and what are their rates of incidence?
Only three autosomal trisomies are capable of producing a live birth.
* Trisomy 13 (Patau syndrome) – frequency 1/22,700 live births
* Trisomy 18 (Edward syndrome) – frequency 1/7,500 live births
* Trisomy 21 (Down syndrome) – frequency 1/580 live births
107
Are most sex chromosomal aneuploidies viable or inviable?
Viable.
108
What are the most common aneuploidies in females, what are they called, and what are their rates of incidence?
Turner syndrome – monosomy X (45,X), 1/4000 female births
Trisomy X – (47,XXX), 1/900 female births
note:Total of all X chromosomal aneuploidies – 1/580 female births
109
What are the most common aneuploidies in males, what are they called, and what are their rates of incidence?
Klinefelter syndrome – (47,XXY and 48,XXXY), 1/1000 male births
47, XYY syndrome – 1/1000 male births
note:Total of all X or Y aneuploidies – 1/360 male births
110
What is the notation for someone born with Down Syndrome?
47, XY+21
111
What is the most common cause of aneuploidy?
A frequent cause of aneuploidy is meiotic nondisjunction.
112
What is the result of disjunction in meiosis 1?
Nondisjunction in meiosis I produces gametes with one maternal copy and one paternal copy of the extra chromosome (and also gametes with zero copies of either).
113
What is the result of nondisjunction in meiosis 2?
Nondisjunction in meiosis II produces a gamete with either two maternal or two paternal copies of the extra chromosome, 2 with one copy of the other chromosome, and one gamete with no copies of the chromosome which underwent nondisjunction.
114
What are some examples of chromosomal abnormalities which do not come from nondisjunction?
Balanced or unbalanced rearrangements.
115
What is a balanced rearrangement? Give examples of types of balanced rearrangements.
A balanced rearrangement takes place when large portions of a chromosome move but no genetic material is lost.
Types of balanced rearrangements:
1. Chromosomal inversion-when a segment of a chromosome inverts, but stays in the same chromosome.
* Peracentric inversion: When the inversion takes place on one side of the centromere.
* Pericentric inversion: When the inversion takes place around the centromere (genetic material from p is now on the q arm, and vice versa)
2. Balanced translocations-when a segment of DNA from one chromosome switches with a segment of DNA from another chromosome.
116
What is an unbalanced rearrangement? Give some examples of unbalanced rearrangement.
An unbalanced rearrangement is a change in a chromosome which causes the loss of genetic material.
Examples:
Insertion
Deletion (terminal vs interstitial)
unequal crossing over
isochromosomes (deletion of one arm and duplication of the other).
Ring chromosomes
117
What are some consequences of unbalanced rearrangements?
Loss of genetic material.
Partial monosomy or trisomy.
Poor disjunction (ring chromosomes)
118
What are some consequences of balanced rearrangements?
The gametes of a person with a balanced rearrangement may or may not be viable, depending on if they are also balanced in terms of genetic material.
This depends on how the chromosomes segregate.
119
What is a Roberstonian translocation?
When the satellites of two chromosomes are lost, and the resulting partial chromosomes fuse.
120
