Chromosomes

Question 1

What does mitosis produce? Describe the stages of Mitosis and what occurs in each stage

Answer 1

Mitosis: provides 2 daughter cells with the same chromosome of the parents
Stages of Mitosis
1. Prophase
-Chromosmoes condense and become visible
-Centromeres move apart towards opposite poles and generate new microtubules
-Nucleoli begin to disappear
2. Prometaphase:
-Nuclear envelope breaks down
-Microtubules from the centromeres invade then nucleus
-sister chromatids attack to microtubules from opposite centromeres
3. Metaphase;
-Chromosomes align on the metaphase plate with sister chromatids facing opposite poles
4. Anaphase:
-centromeres divide
-The now separated sister chromatids move to opposite poles
(so that each daughter cell will have copy 2 copies of chromosome 1 and chromosme 2)
5. Telophase
-Nuclear membranes and nucleoli reform
-spindle fibers disappear;
-chromosomes uncoil and become a tangle of chromatin
6. Cytokinesis:
-The cytoplasm divides, splitting the elongated parent cell into two daughter cells with identical nuclei

Question 2

What occurs in homologous recombination and meiosis I?

Answer 2

Meiosis I: after getting chromosomes duplicating, the maternal and paternal chromosomes pair with each other (may exchange DNA) and then separate form each other
so 4 copies of chromosomes (on top; 4 copies on bottom)
The chromosome pairs will separate
1 daughter cell will get paternal chromosome 1 and other daughter cell will get maternal chromosome 1
-For chromosome 2, it occurs independently so we do not know if paternal chromosome 2 will both end up in same daughter cell or not (random; based on mendel’s laws)
Homologous recombination: will be discussed later

Question 3

What occurs in Meiosis II?

Answer 3

Meiosis II: Take the 2 cells formed in Meiosis I and undergo divisions. Then separate sister chromatids to form haploid gametes.
These will line up on midline, pull apart, and now have 4 cells that have single copy of each chromosome for each cell.
make haploid sperm and haploid eggs. Once they fuse, get a child with 2 copies of every chromosome (that parents had)

Question 4

What is the chromosome theory of inheritance?

Answer 4

The chromosome theory inheritance:
-Chromosomes (like genes) occur in matched pairs
-Chromosome pairs (like genes) segregate from each other when gametes are formed
-Chromsomes are essential for development
*Chromsomes are the underlying physical basis for genes

Question 5

Explain how Karyotypes are prepared and what they are used for .

Answer 5

Preparing Karyotypes;
karyotypes: an individual’s complete set of chromosomes
it is used to know what chromosomes are in our cells (look for any abnormalities in chromosome number or structure)
Process:
-patient will come in and give blood sample (blood drawn)
-Add phytohemagglutin and culture medium to blood sample (culture at 37 degrees C for 3 days )
-Add colchicine and hyptonic saline to fix cells (kill cells)
-when cells are fixed, spread cells onto sides by dropping procedure (look at WBC’s)
-Digest with trypsin and stain with Giemsa
-Analyze metaphase spread (where all chromosomes are scattered in random order)
- Karyotpye made: Cut out pictures of chromosomes and arrange chromosomes in order from biggest (top left) to smallest (bottom right)
-

Question 6

What can be done with chromosomes of mitotic cells? How do you label karyotype?

Answer 6

Chromosomes of mitotic cells can be stained for IDENTIFICATION
-Look at size of chromosome (karyotype arranged from largest to smallest)
-You can count how many chromsomes (should be 46 total chromsomes; 23 pairs that include sex chromosomes XX or XY)
-Observe size and banding pattern of chromosomes with Giemsa dye lets you let you put together karyotype

label karyotype by sex, number of chromosomes and sex chromosomes
ex: Male, 46, XY

Question 7

How many genes are in these chromosomes? provide an example

Answer 7

Each chromosme carries MANY genes
Chromsome 1, have 250 million phase pairs (> 3000 genes)
(hence this chromosome is responsible for a lot of things)

Question 8

Explain the information that is used when describing karyotypes. How do you describe male and female karoytpyes ?

Answer 8

Describing karyotypes:
-The total number of chromosomes is given as a number
-The sex chromsomes are also listed AFTER the number
-Thus a normal male is 46, XY
-And a normal female is 46, XX

Question 9

what is a major change that is seen in karyotypes?

Answer 9

ERROS in the number of chromsome sets

Question 10

What changes in karyotype can rare conceptions (births) produce?

Answer 10

Rare concepts can produce TRIPLOID Fetuses (69, XXX or 69, XXY)
-69 chromosomes with either three X chromosomes or 2 X chromosomes and Y chromosme.

Question 11

Explain why Human Triploidy is usually fatal.

Answer 11

Human triploidy is usually fatal
-About 1-3% of conceptions are triploid
-However, only 0.01% of live births are triploid, so ***MOST of these fetuses are Spontaneously Aborted **
-Rare triploid babies usually die soon after birth, because of numerous developmental disorders
-A few individuals survive longer
triploidy (3 copies of each chromosome; 3x23=69)

Question 12

Explain what can occur with someone who has a tetraploidy. Provide an example.

Answer 12

Tetraploidy is even RARER than triploidy, but does occur
-Tetraploidy is usually fatal, and usually leads to spontaneous abortion
-Some individuals with tetraploidy survive
Ex; Here is a severely disabled child with 92 chromosomes, XXYY (2 X chromosomes and 2 Y chromosomes)
Tetraploidy (4 copies of each chromosome; 4 x 23= 92)

Question 13

What causes triploidy and tetraploidy?

Answer 13

Triploidy and tetraploidy are caused by Multiple sperm
-Usually one sperm reaches the oocyte first
-Its reaction triggers rapid chemical changes that prevent additional fertilizations
-Sometimes multiple sperm fertilize simultaneously
-Sometimes 2 sperm will get through zona pellucida at the same time and cause triploid fetus

Side note:
Normally,The egg is designed so that there will be quick block to fertilization by additional sperm, after first sperm makes it all the way in oopcyte.
The egg (oocyte) have Chemical complex area layer called zona pellucida, where sperm make it up to vicinity of oocyte.
it will get through Zona Pellucida and fuse with cell membrane, cause rapid change (spread of Zinc and Calcium released in Zona Pellucida) which releases chemicals that dramatically change nature of Zona pellucida, make it impermeable to other sperm.
So they will not get through and fertilize

Question 14

Explain why right number of chromosomes is crucial and what may occur if one does not have right number

Answer 14

The right number of chromosomes is crucial
-the individuals with triploidy or tetraploidy have good copies of all important genes
-However, these genotypes are subject to devastating developmental problems
**These differences are likely to be caused by Changing numbers of autosomes compared to single active dose of X *** (dosage problems)
-They might also be influenced by the increase in absolute number of chromosomes
(also too much DNA can cause problem)

Question 15

Why does chromosome dose matter? What happens if you extra autosome? Extra X chromosome?

Answer 15

normal interactions between genes on X and autosome (18)
example: you have 2 X chromosomes. One of them is inactivated, 2 autosomes on chromosome 18. To regulate blue gene, Factors on X compete with factors on autosome to maintain balance

If you have an extra autosome: (ex: someone who is triploid have 69, XXY )
An extra autosome disrupts balance;
- The autosome will makes lots of extra negative regulator, so blue gene gets turned OFF
the red inhibitor (repressor) is winning vs green activator.
-an extra X expression disrupts the balance (too many blue genes made)
-we can avoid this by forming Barr bodies.

Question 16

What happens when there are errors in the number of sex chromosomes? What does this suggest about changes in number of X in flies? How can this be fixed?

Answer 16

rare exceptions in Fly sex-linkage studies:
we could get nondisjunction that causes eggs with an extra X, which after fertilization lead to XXY eggs, or eggs with No X chromosome; Or after fertilization eggs with 1 X or with just 1 Y
in flies, XXX eggs would die, XXY or Single X eggs were okay, eggs with Y were bad and lead to egg being dead (because you cannot live without X)
This suggested that changes in number of X can be harmful to flies
However, Barr body formation in humans can prevent this from occurring.
in humans, an X is turned off, so leave 1 functional X chromosome for each person.
This works if there is 3 X’s (2 X will be turned off) or 4X’s
(This is bad for triploid and tetraploid; unless only X is involved)

Question 17

What does normal progeny look like in sex-linked cross of flies? What does progeny look like for Non-disjunction?

Answer 17

Normal progeny in Sex-linked cross:
after fertilization with egg and sperm:
-Female : XX
Male: XY
Nondisjunction creates RARE progeny
in flies:
after fertilization: get XXX (egg dies), XXY or X which if fine; or Y: bad–> leads to death (since X is needed for life)

Question 18

What occurs in Turner’s syndrome, Patient with XO. What clinical features are present?

Answer 18

XO (Turner’s Syndrome)
-Affects about 1/2500 GIRLS
-Intelligence is usually normal
-Most of the development is also normal, but:
-Ovaries usually degenerate, causing infertility
-About 40% of affected women develop heart problems
-There are often mild abnormalities like extra folds on skin on the neck
XO individual: female

they are normal because they have single X and women have single X working in each cell (although normal women have two)

(in fruit flies, there are males with XO)

Question 19

What are the clinical features of Triple X syndrome (XXX)? what causes this disorder?

Answer 19

XXX (Triple X Syndrome)
-Affects 1/1000 GIRLS
-very mild symptoms:
-often taller than normal
-Usually few problems
-sometimes learning disabilities
Usually caused by SPONTANEOUS problem in Meiosis in a parent
(these individuals have two copies of every other chromosome, but three X’s)
(mild symptoms because in every cell two X’s turned off and only 1 X is functioning just like in normal women)

Question 20

What occurs in XXY (Klinefilter syndrome) What are the clinical features?

Answer 20

XXY (Klinefelter syndrome)
-one extra X present
-Affects more than 1/1000 BOYS and Men
-These individuals are male because of the SRY gene on Y chromosome
(Y chromosome determines the sex)
-Often TALLER than normal
-Usually they have normal intelligence, but they sometimes have mild learning disabilities
-(Barr body can occur in males if X is to be inactivated)

Question 21

Explain how Klinefelter syndrome can affect testosterone production? What are the effects of this? How can this be treated?

Answer 21

Klinefelter syndrome can LOWER testosterone production
-They produce less testosterone than usual:
-Less pronounced male traits
-often causes infertility
The risk of some diseases is similar to that of women:
-Lupus
-Breast Cancer
These problems can be treated with hormone therapy (to supplement production of testosterone, ensure more normal levels)

Question 22

What kind of effects do errors in number of sex chromosomes have?

Answer 22

Errors in the Number of Sex chromosomes have MILD Effects
-since Humans are already designed so that XX and XY individuals are both healthy
-The dosage compensation method ( form Barr bodies; inactive extra X’s) that allows this also protects individuals with the wrong number of chromosomes
-Sexual development is initiated by a single gene on y chromosome, so individuals with a Y are almost always male
-However, these chromosomal errors often affect the GONADS.
(hence can affect fertility)

Question 23

What occurs if there are errors in Autosome number?

Answer 23

Nondisjunction can also cause errors in autosome numbers:
When Meiosis occurs, so you have two pairs of autosome at top
Meiosis I: normally two pairs of autosomes should separate from each other
With nondisjunction, these pairs of autosome will not separate and in Meiosis II, you will end up with 1 cell (oocyte) with neither chromosome in it and another cell with 2 gametes of 2 copies of chromsome 1.
-When the empty cell is fertilized with. normal gamete, it will lead to MONOSOMY
-With other cell containing 2 copies of chromosome 1, and it fertilizes with normal gamete it will result in TRISOMY (3 copies of chromosome)

However, if two pairs of autosomes separated correctly during Meiosis I, you willet one pair of chromosome in each cel
If Nondisjunction occurs during Meiosis II, you will have 1 gamete with NO chromosomes and another gamete with 2 copies of chromosome
-The empty gamete will fertilize with normal gamete and result in MONSOMY
The gamete with two copies of chromomse will fertilize with 1 normal gamete and result in TRISOMY
Hence nondisjunction applies to fruit flies, humans, X chromsome or any chromosome

Question 24

Explain how human oocyte development works

Answer 24

Human oocyte Development
-Female Gametogenesis: production of oocytes for reproduction in females
1. First, get primordial oocyte that duplicates its DNA, chromosomes condense and enter prophase 1
2. then chromosomes line up and get recombination. They will line up metaphase 1 and stay there for a long time
3. Eventually you complete metaphase 1, divide and one daughter will become polar body and die
4.Then go through meiosis II, one daughter become polar body dies and have mature oocyte
-Female meiosis: 1 oocyte and three polar bodies
-There is a Huge delay in process
oocytes will arrest in meiosis I for decades .

Question 25

Explain why oocytes arrest in Meiosis I for decades.

Answer 25

Oocytes arrest in Meiosis I for decades
- any females, every egg produced was initially made and started on pathway to maturation before birth.
Women only make eggs when they are fetuses
-Those eggs then wait arrested in meiosis throughout life
-Hence someone 40 years old and conceives a child, the egg was waiting for 40 years
**As oocytes have to arrest for decades, there is room for chromosomes to get lost or mishandled as eggs are stored for decades. **
**This may explain why risk of nondisjunction increases with age for women (as woman grows older, her oocytes grow older, and oocytes have higher failure retaining chromosome).

(Hence oocytes are initially produced in fetus and remain arrested for a long time until each month after puberty where one primary oocyte gets signal to mature and lead to fertilization )

Question 26

What are trisomies and how do they affect individuals? Which chromosomes can produce trisomies? When can other trisomies occur?

Answer 26

Most Trisomies are FATAL
-A trisomy is an extra copy of a single chromosome, without affecting the remaining ones
-Trisomies change the relative expression of many genes, which can lead to serious problems.
Although there are 22 autosomes, only THREE can produce trisomies:
- 13 (Patau syndrome)
-18 (Edwards Snydrome)
-21 (Down’s syndrome)
-Other trisomies and monosomies occur at fertilization, but lead to miscarriages

Question 27

What kind of trisomy causes Down syndrome?

Answer 27

Trisomy 21 causes Down syndrome
-One of the most frequent chromosomal abnormalities, affecting 1/1000 live births
-many additional Trisomy 21 conceptions undergo spontaneous miscarriages
-Some symptoms are shared by all parents and others are variable.
(down syndrome can be serious enough to cause death in some births)

Question 28

What are the major symptoms of Down’s Syndrome?

Answer 28

Major Symptoms of Down’s syndrome:
-Mental impairment (can be variable)
-Understand language, but problems with speech
-Stunted growth
-umbilical hernia
-Low muscle tone
-flexible ligaments
-Altered ear shape
-Congenital heart disease

Question 29

Explain what happens to risk of Trisomy 21 with mother’s age?

Answer 29

The risk of Trisomy 21 INCREASES with the mother’s age
(risk of nondisjunction increases over time)
low risk of having child with trisomy 21 for women in teens, or 20s. But the risk climbs as women approach 45 years old.
increase in risk of Trisomy 21: reflects problem with keeping oocytes functional and preventing nondisjunction
(still 3% of live births; most of live briths do not have disorder)

Question 30

Which trisomy causes Edwards Syndrome? What are clinical symptoms?

Answer 30

Trisomy 18 causes Edwards Syndrome
-Affects about 1/5000 live births
-many others die in Utero
-major symptoms include:
-Small head
-Mental impairment
-Often a cleft palatte
-Clubfeet
-heart and kidney defects
(karyotype useful in diagnosing disorder)

Question 31

Which trisomy causes Patau Syndrome? What are clinical symptoms?

Answer 31

Trisomy 13 causes Patau syndrome
-RAREST, affecting about 1/15,000 live births
-Major symptoms include:
-Late development
-Mental disability
-Low muscle tone
-Small hands
-small ears, head and mouth
-Malformations
-Heart and kidney problems

Question 32

Explain how the effects of Trisomy 13 are extremely variable

Answer 32

symptoms of Trisomy 13 (Patau syndrome) can be variable
ex; 2 individuals
1 relatively normal, other extremely severe fatal defects.

Question 33

Compare and contrast severity of extra chromosome on Sex chromosome vs autosome

Answer 33

In Autosomes, extra chromosmes are FATAL and usually result in death of child, unless its Down syndrome, Patau or Edwards syndrome
Whereas an extra chromosome on sex chromsome (an extra X or Y) is NOT Fatal (due to Barr body; dosage compensation)

Question 34

What are the different kinds of chromosome rearrangements that can occur?

Answer 34

Chromosome rearrangements:
Translocations, deletions, inversions and duplications

Question 35

What is a translocation? What is a reciprocal translocation? Provide an example

Answer 35

Translocations: are chromosomes that carry a piece of another chromosome
(occur when pieces of two chromosomes switch places )
-Reciprocal translocation: a part of one chromosome will be exchanged with another chromosome (switch places)
ex: part of chromosome 11 is translocated with a part of chromosome 5
translocation 5 (piece of chromosome 11 is placed on chromosome 5) and translocation 11

Question 36

Why do translocations occur?

Answer 36

Translocations can occur due to a cell’s complex environment where chromosomes get broken due to Radiation, virus (targets DNA), transposable elements.

(Also a translocation could occur if two chromosomes broke at the same time, and machine that fixes the issue could have mixed up pieces and stuck them together)

Question 37

Explain how people with balanced translocations can make unbalanced gametes

Answer 37

Balanced translocation (a complete set of chromosomes) can make unbalanced gametes (sperm or eggs that are unbalanced)
Ex: balance set in parent with normal chromosome 3 and 6 and translocation 3 and translocation 6. The parents will not pass on full set to child. They can pass down translocation 3 along with normal chromosome 6 since chromosomes sort independently. Hence, half the time, the child have 2 normal copies of 1 chromosome and 1 defective translocation of chromosome by itself (without its compensating partner). So too few genes for pieces missing for chromosome 3 and too many genes for chromosome 6.

Question 38

Explain how balanced translocations can be inherited

Answer 38

Inheritance of balanced translocations
-A parent with a balanced translocation can produce four different types of children
Only two of these four are likely to develop normally
one child can have completely normal chromosomes, another child with healthy balanced set of chromosomes like parent (with translocation red, translocation green), or a child with unbalanced chromosomes (too much of one chromsome; green), and a child with unbalanced chromosmes (too much of red)

being monosomic for entire chromosome is always fatal

Question 39

What is trisomy 21 sometimes caused by?

Answer 39

Trisomy 21 is sometimes caused by an UNBALANCED TRANSLOCATION
Ex: person with trisomy 21 has 3 copies of chromosome 21; 2 normal copies of 21 and third copy has been translocated onto chromosome 14. Hence the three copies of chromsome 21 make it unbalanced

Question 40

Explain how an unbalanced translocation produces a trisomy

Answer 40

in this type of translocation (Robertsonian translocation), Two chromosomes (whole size) will FUSE at their CENTROMERES
-this can happen because in these chromosomes, the centromeres are normally located at one end.
Can result in trisomy 21 and trisomy 13
normally chromosome 13, 14, 12 have short parts on side of centromere and long parts on other side of centromere; hence you can get fusion where short halves are dropped out. (fuse 13 and 14; or 21 and 14 together)
Robertsonian translocations: fuse ENTIRE chromosomes together (will appear in more complex manners)

Question 41

What method is used to map rearrangements of chromosomes? How does this work?

Answer 41

Mapping rearrangements by Comparative Genomic Hybridization
-You can buy Filters that contain an entire human genome organized by chromosomes pieces from companies.
-Filters can have 100 of spots that allows you to set up test for hybridization to see if a person has a normal number of every piece of every chromosome.
Process:
-take test DNA from patient and label it one fluorescent color, by adding fluorescent binding probe
-Normal control DNA will be labeled a different color
-denature them, so strands are separate
-mix them all together in equal amounts and put in filter with them
if test DNA has all right number of chromosomes and normal control DNA, every spot will be bound equally by green and red and give nice yellow fluoresce.
If patient is missing piece of chromosomes, not enough red dye representing that missing piece will be present and there will be more green for normal control, causing green flourescence.
if see red dot, extra DNA, red predominates

Question 42

What are deletions. What genetic disorder is an example of this chromosome rearrangement ?

Answer 42

Deletions: LOSS of a chunk of DNA from a chromosome
: Cri du chat syndrome (caused by deletion)
(ex: part of chromosome 5 has been deleted)

Question 43

What are the clinical symptoms of Sri du chat syndrome ?

Answer 43

Cri du chat Snydrome :
-Affects about 1/35,000 babies
- Infants have a high-pitched cry like a kitten
-intellectual disability
-Microcephaly
-Delayed Development
-Low birth weight
-Weak muscle tone

Question 44

Which scientist pioneered the use of karyotypes in medicine? What were his other discoveries?

Answer 44

Jerome Lejeune pioneered the use of Karyotypes in medicine
-Pioneered the use of cytogenetics to study human disease
-Identified the causes of Down’s syndrome and Turner’s Syndrome (wrong numbers of chromosomes)
Identified a DELETION that causes Cri du chat syndrome

Question 45

What causes Cri du chat Syndrome?

Answer 45

Cri du chat Syndrome causes by the DELETION of part of chromosome 5
**Affected individuals develop abnormally because they are monosomic for a small part of chromosome 5)
They have only single copy of each of the gene in region where deletion occurs.
(nonfatal, cause developmental problems; normal chromosome 5, and deletion portion of chromosome 5)

Question 46

What is another example of a genetic disorder that has deletions? What are its clinical symptoms?

Answer 46

Smith-Magenis Syndrome
-Affects 1/25,000 people
symptoms include:
-intellectual disabilities
-Delayed speech
-Craniofacial abnormalities
-Sleep disturbances
-Behavioral problems
-Typically caused by SPONTANEOUS MUTATIONS
-

Question 47

What causes Smith-Magenis Syndrome?

Answer 47

Smith-Magenis Syndrome is caused by a DELETION on chromosome 17.
caused by internal band in chromosme the is deleted.

Question 48

What is Fluorescence in Situ Hybridization (FISH)? What can it be used for?

Answer 48

Fluorescence In Situ Hybridization (FISH)
use hybridization to chromosmes as you see them in cells
(process of probe DNA and label it with fluorescent dye. You then denature and hybridize strand)

The 17p11.2 Deletion can also be detracted by FISH
-the red marker binds the LIS1 gene in 17p13.3 (chromosome 17) . It labels BOTH copies of chromosome 17
-The Green marker binds the FL1 gene (nearby) in 17p11.2 It only labels the **Normal chromosome 17.
(hence chromsome 17 labeled Only red (not green) has a small deletion )

Question 49

What is another cause of Smith-Magenis Syndrome?

Answer 49

Smith-Magenis Syndrome can also be caused by Mutations in the RAI1 gene
(single mutation in single gene)
-These mutations are DOMINANT alleles of a gene regulated by retinoic acid
-The mutations eliminate the gene product
-This gene might be the key to Smith-Magenis

Question 50

Besides translocations and deletions, what other chromosome rearrangements are possible?

Answer 50

Inversions and Duplications are also possible.
-Inversions: When a piece of chromosome is flipped around within chromosome in itself.
ex: chromosome 3, normal has one arm in purple, other arm in green
-in inverted chromosome 3, a piece of purple arm has been removed and stuck back in the green upper arm of same chromosome.
-Duplications: some DNA from chromosome is copied over.
example: some of chromosome 3 has been duplicated, and some has been deleted.
ex; purple arm of chromsome 3 has been duplicated, green arm of chromosome 3 has been deleted.

Question 51

What kind of effects occur with extra sets of chromosomes?

Answer 51

Extra sets of chromosomes cause very SEVERE effects on human health (due to multiple sperm fertilizing an egg)
-they are invariably fatal (since you cannot inactivate extra autosomes (but you inactivate extra sex chromosme), and due to extra chromosome number)
ex: triploidy, tetraploidy

Question 52

What happens when you alter the number of sex chromosomes? what about have extra copies of single chromosome?

Answer 52

Alter the number of sex chromosomes (3X or 1X), cause mild disorders
most serious effects on FERTILITY
-If have extra copies of single chromosome (autosome)- usually FATAL except for 13, 18 and especially 21 (Down syndrome) –> trisomies
MISSING A copy of an autosome is always FATAL
Down syndrome is most common