Molecular Bio, Cytogenetics, Epigenetics - Assorted Questions

Question 1

Example of disease from terminal deletion?

Answer 1

Cri du Chat syndrome (5p)

Question 2

Example of disease from interstitial deletion?

Answer 2

Williams Syndrome (chromosome 7)

Some other mircodeletions: DiGeorge, Prader-Willi/Angelman, Kallman syndrome

Question 3

3 types of translocations

at least how many breakpoints are required for them?

Answer 3

1. reciprocal (at least 2 breakpoints)
2. Robertsonian/ centric fusion. (at least 2 breakpoints)
3. Insertional (at least 3 breakpoints needed)

Question 4

(Most commonly used) example of reciprocal translocation?

What diseases is it associated with?

Answer 4

Philadelphia chromosome t(9;22)
-> CML, ALL

(other important example is EBV causing translocation of chromosome 8 to 14, 2, or 22, related to Burkitt lymphoma)

Question 5

In which types of chromosomes is Robertsonian translocation able to occur?

Answer 5

Only acrocentric chromosomes (13, 14, 15, 21, 22).

The break is in or near centromere, allows abnormal fusion that results in reduction of total chromosome number by 1
[this is relatively balanced though, so won’t necessarily have a phenotype change. may have problems with meiosis / producing offspring]

Question 6

How many breakpoints are necessary for an inversion?

What are the 2 kinds of inversions?

Answer 6

2 breakpoints, then the segment flips 180 degrees and rejoins in the direction opposite from normal

Can be either pericentric (centromere involved) or paracentric (centromere not involved)

Both can cause problems with meiotic pairing and segregation

Question 7

How does a ring chromosome form?

Answer 7

End-piece genes and telomeres break off, which makes the ends more likely to be “repaired” by coming together and sticking to each other as a loop.

Ring chromosomes are surprisingly mitotically stable

Question 8

How does an isochromosome form?

Answer 8

During mitosis or meiosis II, the long arms stick together to make one chromosome, and the short arms stick together to make another chromosome

Poor prognosis, except for iXq (isochromosome of long arm of X)

Question 9

Most commonly-used examples of monosomy and (autosomal) trisomies?

Answer 9

Monosomy: only Turner syndrome (45, X0), because monosomy of any other chromosome is lethal

Trisomy: Down (21), Edward (18), Patau (13)

Question 10

What is an example of unbalanced Robertsonian translocation?

Answer 10

Down syndrome can also be caused by this (besides trisomy 21) due to excessive 21 translocation

Question 11

What are the sex chromosome trisomies?

Answer 11

XXX: Triple X Syndrome. has 2 Barr bodies. Most probably are not noticed, rarely have problems.

XXY: Klinefelter. Mostly male phenotype yet some feminine features, 1 Barr body, infertile.

XYY: Jacobs. (not really clear if more prone to lower intelligence or higher aggressiveness, flawed research)

Question 12

What is uniparental disomy (UPD?)

What are the 2 numerical aberrations that cause UPD?

Answer 12

One parent’s chromosome is missing, while the others’ is duplicated, so chromosome number is normal.

Meiotic nondysjunction and then anaphase lag

Question 13

Difference between mosaic and chimerism?

Answer 13

Mosaic: within an organism, 2 cell lines of different chromosomes but same origin. Often reduces the effects of genetic diseases if there is some mosaicism.

Chimera: with an organism, 2 cells lines of different chromosomes and different origin (e.g. fusion of twin, double fertilization including a polar body)

Question 14

What is natural microchimerism?

Answer 14

Some fetal cells stay in the mother after birth (detectable in small amount of cells with Y chromosome after having pregnancy with male)

May be responsible for autoimmune diseases

Question 15

What are 3 mechanisms of epigenetic modifications?

Answer 15

1. DNA methylation (cytosine, DNA becomes silenced in hypermethylated areas)
2. Histone modification (acetylation, methylation, phosphorylation, ubiquitination, etc)
3. non-coding RNAs (long non-coding and micro RNAs)

Question 16

What are the enzymes to know that perform DNA methylation?

Answer 16

DNA methyltransferases (DNMT)
-DNMT1: performs methylation on new complementary DNA strands, maintaining the original pattern

-DNMT3A and DNMT3B: methylates cytosines “de novo” - ones that had not been previously methylated

Question 17

How can DNA methylation lead to mutation?

Answer 17

Unmethylated cytosine spontaneously deaminates to uracil, which is not normal in DNA so may be detected and repaired. However, methylated cytosine deaminates to thymine, which is normal in DNA and so it won’t be repaired (new mutation).

Since C normally binds with G while T binds with A, the complementary strand may also transform to match with thymine with adenine.

Question 18

What is a medically important location of CpG islands?

Answer 18

CpG islands (large amount of unmethylated C-G pairs) are frequently found in promoter regions of genes. If they do become methylated, there is higher risk that cytosine can mutate to thymine, and the promoter will be dysfunctional.

Mutations in this region are often not compatible with life

Question 19

What is an example of a disease caused by mutation of a gene for a protein involved in the histone code?

Answer 19

Rett syndrome (MECP2, methylated cytosine bridging protein mutation)

Question 20

How does X inactivation work?

Answer 20

In people with more than 1 X chromosome, inside the XIC (X-inactivation center), the XIST gene (X-inactivation specific transcript) of the INACTIVE chromosome codes for a large non-coding RNA that initiates silencing/ chromosome condensation/ heterochromatization (mechanism not fully understood)

Question 21

What are the pseudoautosomal regions?

Answer 21

Regions of the X and Y chromosomes that are homologous and are needed for normal development (the reasoning why Turner syndrome are abnormal with only one X, and that normal women need 2X)

Pseudoautosomal rgions are identified as PAR1 and PAR2, near the telomeres of both arms of X.

Question 22

What are the differences between Prader-Willi and Angelman syndromes, both genetically and clinically?

Answer 22

Prader Willi:

• Most common cause: paternal 15q11-13 deleted
• Other causes: Wrong imprinting, Maternal uniparental disomy (UPD)
• Fat, small hands/feet, small genitalia, mild mental retardation

Angelman:

• Usually maternal deletion of 15q11-13
• Other causes: wrong imprinting, paternal UPD, UBE3A mutation
• Developmentally retarded, compulsive laughter, poor speech ability

[seems imprinting is always involved, but the way she worded these garbage ppt slides makes that unclear]

Question 23

How many molecules of DNA are present before and after mitosis and meiosis?

Answer 23

92 DNA molecules at beginning of both mitosis and meiosis

At end of mitosis -> two cells with 46 DNA molecules

At end of meiosis I, have 2 cells with 46 DNA molecules. At end of meiosis II, have 4 cells with 23 DNA molecules.

Question 24

What is an example of codominant inheritance?

Answer 24

ABO blood groups. 2 alleles are inherited, and they both influence the production of blood group-determining proteins

Question 25

What are the phases of mitosis?

Answer 25

1. Prophase: Chromatin condenses into chromosomes, centrosomes begin to organize
2. Prometaphase: nuclear membrane disintegrates, nucleolus dissapears, kinetichore microtubules arrange to the centromeres
3. Metaphase: chromosomes are arranged, ready to split
4. Anaphase: sister chromatids split, move away
5. Telophase: kinetichore disappears, nuclear membrane reforms, chromosomes decondense

Question 26

What is the effector protein of the G1 checkpoint? and the G2 checkpoint?

Answer 26

G1: p53
G2: Cdc25

Question 27

What is a micronucleus?

Answer 27

A small DNA fragment seen in the cytoplasm. Its presence shows higher incidence of mutations, and is used to test mutagenicity of substances.

Question 28

What are the phases of meiosis I prophase?

Answer 28

1. Leptotene: the 2 sister chromatids bind their ends to the nuclear envelope, and homologous chromosomes move towards each other
2. Zygotene: pairing/synapse begins w/ synaptonemal complex forming
3. Pachytene: crossing over occurs, “bivalent” is formed
4. Diplotene: synaptonemal complex dissociates, sites of crossing over (“chiazma”) are all that link homologous chromosome pairs
5. Diakinesis: nuclear membrane fragments, prophase ends

Question 29

What is the name of the sites of chromosomal crossing over during meiosis I?

Answer 29

Chiazma

Question 30

What separates during anaphase of mitosis, meiosis I, and meiosis II?

Answer 30

Mitosis: sister chromatids separate. 2n, 4C -> 2n, 2c

Meiosis I: homologous pairs separate (sister chromatids remain together). 2n, 4C -> 1n, 2C

Meiosis II: sister chromatids separate. 1n, 2C -> 1n, 1c

Question 31

2 mechanisms in meiosis that increase genetic variation

Answer 31

1. Crossing over in meiosis I prophase

2. Meiosis I anaphase random separation of chromosomes

Question 32

Ratio of chromosomal abnormalities after meiotic nondysjunction in meiosis I vs meiosis II

Answer 32

Meiosis I NDJ: 2 trisomy, 2 monosomy

Meiosis II NDJ: 1 trisomy, 1 monosomy, 2 euploidy

Question 33

What phase do primary oocytes stay in until they are matured before ovulation?

What phase is the ovulated oocyte stuck in until fertilization?

Answer 33

First stuck in meiosis I prophase diplotene

Later stuck in meiosis II metaphase

Question 34

Just be aware that I didn’t make detailed cards about molecular biology because I find it really painfully detailed, but they seem to love questions about MPF and the centrosome. Questions about that kind of stuff from the first few chapters is under-represented in here

Answer 34

Godspeed