Inherited Disease

Question 1

List the 4 ways an X-linked recessive condition can affect females

Answer 1

Female is daughter of affected father and carrier mother
In XO (Turners Syndrome)
In skewed lyonisation
If there is an x chromosome autosome translocation

Question 2

Describe the two types of heterogenecity

Answer 2

ALLELIC
Different mutations in the same gene cause a similar or different phenotype of a disease
LOCUS
Mutations in different genes cause the same clinical syndrome

Question 3

In the classification of birth defects, what is a malformation?

Answer 3

Has an underlying genetic cause e.g. cleft palate

Question 4

In the classification of birth defects, what is a disruption?

Answer 4

Normally programmed development disrupted by external agent e.g. teratogenic drug or vascular occlusion e.g. fetal alcohol syndrome

Question 5

In the classification of birth defects, what is a deformation?
AND Describe Potters Sequence

Answer 5

Normal development “deformed” by mechanical forces e.g. amniotic bands
Potters Sequence - compression deformations from oligohydraminos

Question 6

Define Aneuploidy

Answer 6

The presence of an abnormal number of chromosomes in a cell

Question 7

Describe chromosome translocation

Answer 7

Rearrangement of parts between NON-HOMOLOGOUS chromosomes
They can be BALANCED i.e. even exchange of material with no genetic information missing or extra
or they can be UNBALANCED which results in missing or extra genes

Question 8

Describe Reciprocal Translocation and their significance

Answer 8

Occurs when two fragments break off from two different chromosomes and swap places.
Carriers of balances reciprocal translocations are at increased risk of creating gametes with unbalanced chromosome translations leading to miscarriages or children with abnormalities.

Question 9

Describe a Robertsonian Translocation

Answer 9

Occurs in acrocentric chromosomes i.e. 13, 13, 15, 21, 22
These chromosomes have normal q arms, but very short p arms. During a Robertsonian Translocation the q arms join together to form a very long chromosome and the shorter p arms are lost from the cell. The cell ends up with only 45 chromosomes

Question 10

Describe what happens in chromosome microdeletions and give some examples

Answer 10

Chromosomal deletion (

Question 11

Describe the different antenatal genetic tests available

Answer 11

CHORIONIC VILLOUS BIOPSY
performed between 11 and 13 weeks (first trimester)
AMNIOCENTESIS
Most commonly performed at 15-18 weeks gestation (can be done earlier if preferable to CVS e.g. in twin pregnancies but higher risk of miscarriage)

Question 12

Describe the Founder Effect

Answer 12

Over representation of a gene defect in a small community

Question 13

What is the key aspect to look for on a pedigree in X-Linked Dominant transmission

Answer 13

There will be no male to male transmission, and all the daughters of an affected father will be affected.
(whereas in Autosomal Dominant you would expect to see this by chance)

Question 14

Describe Gowers Sign

Answer 14

Gowers’ sign is a medical sign that indicates weakness of the proximal muscles, namely those of the lower limb. The sign describes a patient that has to use their hands and arms to “walk” up their own body from a squatting position due to lack of hip and thigh muscle strength

Question 15

What is the name of Trisomy 13

Answer 15

Patau Syndrome

Question 16

What is the name of Trisomy 18

Answer 16

Edwards Syndrome

Question 17

Describe how X-chromosomes are inactivated.

Answer 17

XIST = functional RNA on X chromosome

If XIST is transcribed, XIST RNA coats the x-chromosome and silences it (exclusion of PAR regions)

Question 18

Describe how X Chromosomes prevent themselves from becoming inactivated

Answer 18

If you add METHYL group to X chromosome, XIST cannot be transcribed and X remains activated

Question 19

Describe how female carriers can display phenotype through x-inactivation

Answer 19

More of normal X inactivated = skewed lyonisation
Abnormal X in transcribed, abnormal trait allowed in cell
SO get mosaicism
The more normal x inactivated, the more severe the phenotype –> -most severe described to have an x-linked dominant mode of inheritance

Question 20

Describe the imprinting in Prader Willi

Answer 20

Normally silence maternal copy of that gene region

Meaning you inherit the mutation from paternal DNA

Question 21

Describe the Imprinting in Angelman Syndrome

Answer 21

In Angelman syndrome the paternal copy is silenced

Meaning you inherit the mutation from maternal DNA