Chromosomal Disorders

Question 1

Change in the quantity of DNA in the genome that can lead to mutant phenotype. Give an example of this.

Answer 1

Down Syndrome - Caused by an extra copy of human chromosome 21

Question 2

Change in the location of a DNA sequence that can lead to a mutant phenotype. Give an example

Answer 2

Muscular dystrophy can be caused by the breakage and relocation of a segment of the human X chromosome

Question 3

A change in a DNA sequence that can lead to a mutant phenotype

Answer 3

Triplet repeat expansion mutations in a gene causing abnormal protein product (Huntington’s disease), sickle-cell anaemia (single bp substitution)

Question 4

How many pairs of chromosomes do humans have?

Answer 4

23

Question 5

How many pairs ofautosomes do humans have?

Answer 5

22

Question 6

What is a karyotype?

Answer 6

A karyotype is a display of chromosomes paired according to their size, location of the centromere, and staining patterns

Question 7

What is amniocentesis?

Answer 7

Amniocentesis uses a needle to extract amniotic fluid from the uterus of a pregnant woman from the 14th to 17th week of pregnancy

Question 8

What is a safer option than Amniocentesis?

Answer 8

Chorionic villus sampling

Question 9

Outline the basic procedure for human karyotype preparation

Answer 9

Mitosis is stimulated then arrested in metaphase (form sister chromatids)
During mitosis the pairs of chromosomes condense and become visible under a light microscope
The condensed chromosomes are then stained with Giemsa dye
The dye stains areas of the chromosome rich in Adenine and Thymine base pairs, producing characteristic dark bands

Staining the chromosomes results in a smear which is then photographed
From analysis of the length of chromosomes, bands and location of centromeres, a karyotype can be assembled
In a normal case, there will be 46 chromosomes I.e. 23 pairs
Study of a karyotype can determine whether an adult’s chromosomes contain an abnormality which could be passed on.
Karyotypes can be useful for determining the possible cause of infertilty or miscarriage
Karyotyping is also a good test for chromosomal abnormality in a foetus or identifying the cause of a baby’s birth defects

Question 10

What is the specific notation for karyotyping?

Answer 10

First, the total number of chromosomes
Next, the sex chromosomes
Then any extra or missing autosomal chromosomes
Examples:
46, XX is female with a normal number of chromosomes
47, XY +18 is male, and has an extra autosomal chromosome 18
46, XY del (7q) is male missing part of long arm of chromosome 7

Question 11

What does Euploidy mean?

Answer 11

Euploidy refers to a normal set of chromosomes (i.e. 23 pairs, 2n)

Question 12

What does polyploidy mean?

Answer 12

Polyploidy refers to one or more extra sets of the entire genome (3n, 4n etc)
Polyploidy does not exist in humans
Polyploids can be nearly normal phenotypically. Maybe this is because the normal genetic ratio (or balance) is maintained when there is an entire extra set.
One more or one less chromosome disrupts genetic balance far more than does an entire extra set of chromosomes.

Question 13

What does aneuploidy mean?

Answer 13

Aneuploidy refers to an abnormal chromosome number

Question 14

How does nondisjunction occur?

Answer 14

Nondisjunction occurs when members of a pair of homologous chromosomes do not move apart properly during meiosis I or fail to separate during meiosis II
In both cases of meiotic error gametes with abnormal chromosome number will be produced
One gamete will receive 2 copies of the same chromosome
The other gamete will receive no copy

Question 15

What would trisomy 18 mean?

Answer 15

If a chromosome is present in triplicate in a cell the cell is trisomic for that chromosome.

Question 16

What would monosomy X mean?

Answer 16

If a chromosome is missing from a cell, the cell is said to be monosomic for that chromosome.

Question 17

Name 4 aneuploidy syndromes that can go to term?

Answer 17

Down syndrome (Trisomy 21)
Patau syndrome (Trisomy 13)
Edward syndrome (Trisomy 18)
Syndromes related to sex chromosomes

Question 18

When was Down syndrome first described?

Answer 18

1866

Question 19

How many births are affected by Down Syndrome?

Answer 19

1 in 700

Question 20

What causes Down Syndrome?

Answer 20

90% of these are due to nondisjunction during meiosis I in the oocyte; the other 10% are due to nondisjunction in meiosis I or II in males.
Although chromosome 21 one of the smallest chromosomes, trisomy 21 severely effects the individual’s phenotype

Question 21

What are the symptoms of Down Syndrome?

Answer 21

characteristic facial features, short stature, epicanthal folds, mental retardation

Question 22

What problems are associated with someone with Down Syndrome?

Answer 22

Susceptibility to heart defects, leukaemia and Alzheimer’s disease
Most Down syndrome individuals are sexually underdeveloped and sterile.
Although there is generally a shorter lifespan, some do live to middle age
Frequency of Down Syndrome increases with the age of the mother, from the age of about 30 onwards.

Question 23

Trisomy 13 leads to what syndrome?

Answer 23

Patau Syndrome

Question 24

How common is Patau Syndrome and what is the survival rate?

Answer 24

Very rare occurring in only 1 in 15,000 live births. Most cases die in utero.
The survival rate of Patau syndrome individuals is low. 50% of live births die within 1 month; most do not survive longer than 6 months

Question 25

What are the symptoms of Patau Syndrome?

Answer 25

mental retardation
Microcephaly
cleft lip/palate
micrognathia
deformed, low-set ears, nose
Polydactyly. Heart defects

Question 26

What is trisomy 18?

Answer 26

Edward Syndrome

Question 27

How common is Edward Syndrome and what are the survival rates?

Answer 27

Very rare - 1 in 10,000 live births. most die in utero

The survival rate also low. Most do not survive longer than 6 months, though a few do live to adolescence

Question 28

What are the symptoms for Edward Syndrome?

Answer 28

mental retardation
 short neck
 cleft lip/palate
 dislocated hips/abnormal pelvis
 deformed, low-set ears
 Congenital heart disease

Question 29

Nondisjunction of sex chromosomes also produces aneuploid conditions in humans.
Most of these seem to cause a less severe upset to the genetic balance than autosomal aneuploid conditions like Patau syndrome do.Why?

Answer 29

Y chromosome carries relatively few genes, so there are less genes affected by an abnormal number.
Also, in the case of the X chromosome (which does code for many genes), extra X chromosomes become inactivated as Barr bodies in somatic cells.
Very few genes are expressed from these Barr bodies.

Question 30

Give examples of aneuploid of sex chromosomes

Answer 30

Syndromes involving aneuploidy of the sex chromosomes include Klinefelter Syndrome and Turner Syndrome

Question 31

Describe Klinefelter syndrome

Answer 31

Klinefelter syndrome (XXY) results from non-disjunction of the X chromosome. The presence of the Y chromosome means the individual is classed as male, but with an extra X chromosome.
Quite rare, occurring once very 2000 live births
Individuals are phenotypically male with male sex organs but have small testes and are sterile.
During puberty they tend to develop feminine body characteristics.
However, unlike with the autosomal aneuploidies, Klinefelter individuals are usually of normal intelligence
Males with XYY are not characterised by a defined syndrome.

Question 32

Describe Turner Syndrome

Answer 32

( 45, X0). Individuals only have 1 X chromosome.
Only once in every 5000 births
Turner syndrome is the only known viable monosomy in humans
Turner syndrome individuals, being X0, are phenotypically female, but sex organs do not mature at adolescence, and they are sterile.
Can be treated with oestrogen replacement therapy and go on to develop secondary sexual characteristics
Most have normal intelligence.
There is a trisomy associated with the X chromosome. Females with trisomy X (XXX) occur 1 in 1000 births.
Females with trisomy X appear to be completely healthy and can only be distinguished from normal XX females by karyotype!

Question 33

What is the name of a syndrome related to a deletion of an allele?

Answer 33

Cri du chat - Caused by a deletion of an end piece of chromosome 5.

Question 34

Symptoms of Cri du chat syndrome

Answer 34

Mental retardation
Small head
Facial abnormalities

Question 35

What happens when you have a short chromosome 22?

Answer 35

Chronic myelogenous leukeamia
CML causes cancer of WBC’s
Reciprocal translocation of portion of chromosome 22 and bit of 9