Chromosome Abnormalities

Question 1

How many chromosomes do we have

Answer 1

22 autosome pairs
two sex chromosomes
46 total

Question 2

What is the function of the centromere and what is it made of?

Answer 2

Joins sister chromatids

comprises of 100’s of Kilobases of repetitive DNA (constutive heterochromatin)

Question 3

What are the two chromosomes arms called and what is at the end of the chromosomes?

Answer 3

p (petite) small arm
q = large arm

Telomeres that act as a cap (repeating non coding DNA)
protects genes from enzymatic attack

Question 4

What are the light and dark bands?

Answer 4

Light bands are gene rich and contain less dense chromatin

Dark bands less gene rich, densely packed chromatin

Question 5

How is a karytoype made?

Answer 5

cell sample taken

cells grown in tissue culture treated with phytohemagluttinin that triggers mitosis

colchicine is then added to prevent spindle fibre formation and halt mitosis (stuck in M phase)

cells paced in salt hypotonic solution –> water moves into cell they swell chromosomes separate more

Sainted with giemsa

arranged using light microscopy according to size and banding pattern into homologous pairs to produce a karyotype

Question 6

Advantages and Disadvantages of Karyotypes

Answer 6

allows you to easily see that the number of chromosomes present is correct and any major translocations or deletions insertions that may have occurred

Disadvantage
cannot see individual genes and is not very detailed
is time consuming and expensive

Question 7

What is FISH?
How does it work?
Why is it used?

Answer 7

Fluorescent in situ hybridisation

uses fluorescent probes to bind to chromosomes at a high degree of sequence similarity
used to identify translocations and whether particular sequences are present or absent due to deletions or insertions

has a much higher resolution. than a karyotype and identifies chromosomes with certainty

Question 8

What is array CGH?
How does it work?
Advantages of this method?

Answer 8

array comparative gene hybridisation

Patients DNA is fixed onto a glass slide and then fluorescently labelled one colour (green)

normal reference DNA is placed on same slide and labelled with another colour (red)

Compete with specific hybridised probes
if equal amount of chromosome are present then the slide will be yellow
if they are parts of chromosomes missing the slide will be red
if there are extra parts of chromosome they will be green

most commonly use
greater resolution allows you to detect all changes in small sections of a chromosome

Question 9

What are the two types of chromosomal abnormality

Answer 9

Numerical abnormalities:
Aneuploidy trisomy (3) or monosomy (1)
Polyploidy increase in overall chromosome no e.g 69 Triploidy

Structural chromosome abnormalities:
translocations
deletions
duplications
inversions

Question 10

How would you write the chromosomes of a normal male

Answer 10

46, XY

Question 11

What is 47, XX, +21

Answer 11

A female with Downs Syndrome

Question 12

How would you write a female with Tuners syndrome

Answer 12

45, X

Question 13

What is Downs syndrome

Answer 13

trisomy in chromosome 21

Question 14

Edwards syndrome

Answer 14

Trisomy chromosome 18

Question 15

Patau syndrome

Answer 15

Trisomy chromosome 13

Question 16

What is Turners syndrome?

Symptoms?

Answer 16

females only have one X chromosome

results in short stature infertility delayed onset no onset of secondary sex characteristics

Question 17

What is Kleinfelters syndrome?

Answer 17

Males have an extra X chromosome

Results in
issues with fertility delayed puberty development of poor secondary sex characteristics

Question 18

Why are trisomies a problem?

Why don’t any other trisomies occur and why don’t you get people with monosomies?

Answer 18

results in gene dosage problem there are too many gene products leading to significant developmental issues

All other trisomies are incompatible for life
All monosomies are incompatible for life

effects of reducing gene copy more severe than increasing it

Question 19

Down Syndrome incidence & clinical sings

Answer 19

1 in 700 live births

single palmar crease

small ears and mouth upward slanting nose and eyes

delayed development and metal handicap

white sports on iris

Question 20

What are the possible causes of Down Syndrome

Answer 20

Trisomy in chromosome 21 (95%)

4% due to a Robertsonian translocation that results in trisomy

1% have mosaicism one normal cell line and one Downs cell line usually have milder symptoms

Question 21

Why do Trisomies occur?

Answer 21

Due to non-disjunction

Question 22

What is non-disjunction when can it occur

Answer 22

failure of homologous chromosomes to separate during meiosis I
Daughter cells (2 n+1 and 2 n-1)

or

non-disjunction as a result of failure of sister chromatids to separate during meiosis II
Daughter cells (n+1, n-1< and two normal haploid n)

Question 23

incidence of non-disjunction

Answer 23

Increases with increased maternal age

longer oocytes have been left in the dormant stage of meiosis I thought to lead to damage to spindle fibre production and repair mechanisms as woman ages predisposing oocyte to non-disjunction

Question 24

Edwards and Patau syndrome incidence and symptoms

Answer 24

Edwards 1 in 3000
multiple heart and kidney malformations

Patau 1 in 5000
multiple malformations

Both have poor prognosis baby dies in first few weeks
if they survive have sever mental retardation

Question 25

Implications for genetic counselling regarding trisomies ?

Answer 25

Aneuploidy is as a result on meiotic non-disjunction related to maternal age therefore risk of recurrence is low

non-disjunctions are not inherited

Question 26

What are the acrocentric chromosomes?

What do they look like

Answer 26

13,14,15,21,22

Centromere positioned high up resulting in very small short arm that has no coding DNA

Question 27

What is a Robertsonian translocation?

Answer 27

only involves acrocentric chromosomes

involves the breaking os two acrocentric chromosomes and the fusion of the long arms to form a metacentric chromosome as well as two other normal copies of each chromosome

(short arms are lost no effect just repeat sequences)

Question 28

What is a balanced Robertsonian translocation

Answer 28

Have two copies of each chromosome yet they are just arranged differently

There is no effect on phenotype as there is no gene imbalance

Question 29

Why is being a balanced Robertsonian carrier significant?

Answer 29

More at risk of having a child who has an unbalanced Robertsonian Translocation

Question 30

What is an unbalanced robertsonian translocation?

What fate does a zygote have?

Answer 30

Two copies of one chromosome (normal) and three copies of another

This leads to monosomy or trisomy in the gametes both of which are fatal
Trisomy in chromosome 21 is compatible with life and so is 13 however child has Downs Syndrome or Patau syndrome

Question 31

What is a give away of Robertosonian translocations in family histories?

What genetic counselling should be done?

Answer 31

Miscarriages
as most combinations prove to be fatal in unbalanced translocations

Should advise carriers if that they are at an increased risk of miscarriages or a baby with Down syndrome/ Patau syndrome

Question 32

What is a reciprocal translocation?

Answer 32

Breakage of two non homologous chromosomes with an exchange of fragments
(can happy between any two non paired chromosomes)

Question 33

What is the effect of a balanced reciprocal translocation?

Answer 33

No effect
there is no gene imbalance the gene dosage remains the same both copies of chromosome are present just arranged differently

occurs in 1/500 people

Question 34

What is significant about being a carrier of a reciprocal translocation?

Answer 34

increased risk of producing unbalanced gametes during meiosis

Question 35

Offspring possibilities of a balanced carrier and normal induvidual?

Answer 35

Normal 1/4 no risk

Balanced carrier 1/4 normal increased risk of offspring having unbalanced translocation

Partial Trisomy lethal unbalanced

Partial monosomy lethal unbalanced

Some may survive is imbalance is small but with have very severe malformations and developmental delay

Question 36

Why is genetic counselling for reciprocal translocations tough?

Answer 36

Size and position of segments involved in translocations have varying effects on the paring of chromosomes during meiosis and thus the risk of the child being unbalanced
Most couples have prenatal testing

Question 37

What is the effect of large chromosome deletions or duplications

Answer 37

occurs due to misparing during meiosis often at a series of repeat sequences
leads to imbalance in genes and will vary in severity on how much is deleted inserted

chance of recurrence is low

Question 38

What is mosaicism

What are the two types

Answer 38

Having two populations of cells with different genetic constitution due to and error in mitosis that occurs after fertilisation

Is Rare

Somatic two different populations of cells within the body (Downs syndrome population normal population)

Gonadal two cell population in the gonads no influence on phenotype but can be passed on