Pedigrees of Genetic Diseases

Question 1

What are the 3 common types of single gene disorders?

Answer 1

Autosomal Dominant
Autosomal Recessive
X-Linked

Question 2

If someone has an autosomal dominant disorder, what have they inherited?

Answer 2

1 copy of the altered gene from 1 parent.

They are heterozygotes

Question 3

If someone has an autosomal recessive disorder, what have they inherited?

Answer 3

2 copies of the altered gene from each parent.

They are homozygotes

Question 4

Who is affected by an X-Linked recessive disorder?

Answer 4

Males only.

Inherited on X chromosome from mother.

Question 5

Give an example of autosomal dominant condition?

Answer 5

Any from:
Huntington disease
Marfan Syndrome
Familial hypercholesterolemia
Prader-willi

Question 6

Give an example of an autosomal recessive condition?

Answer 6

Any from:
Sickle cell disease
Cystic Fibrosis
Phenylketonuria
MSUD

Question 7

Give an example of an X-Linked recessive condition?

Answer 7

Any from:
Fragile X syndrome
Haemophilia
Ocular Albinism
Duchennes Muscular Dystrophy

Question 8

Why is taking a family history important when assessing someone for a possible genetic disorder?

Answer 8

They may have history of the disorder in their family which makes them and possible future offspring more likely/at risk of inheriting the disorder.
Then further steps and advice can be given to the patient accordingly.

Question 9

What is another name for a family tree showing inheritance called?

Answer 9

Pedigrees

Question 10

The pedigree of an autosomal dominant condition has what characteristics?

Answer 10

Vertically inherited down generations
Unaffected individuals don’t produce affected offspring
There is male-male and male-female inheritance so it is not X-linked

Question 11

The pedigree of an autosomal recessive condition has what characteristics?

Answer 11

Equally transmitted by men and women
Horizontal inheritance pattern
If children are affected then the parents must be either carriers or affected

Question 12

What does a triple repeat disorder mean?

Answer 12

There is a piece of repetative DNA within the affetced gene or near the affected gene.
It gets worse over time and through generations.

Question 13

What are the common features of triple repeat disorders?

Answer 13

Triple repeats show instability as they typically expand
Decreased age of onset when they expand
Repeat expansion occurs during subsequent generations (anticipation)
Parental origin influences anticipation.

Question 14

What is meant by anticipation?

Answer 14

The age of onset for triple repeat autosomal dominant disorders becomes earlier and earlier as time goes on and severity of the disease increases so we anticipate if someone has the disorder.
Anticipation is because of the expansion of the triplet repeat over generations

Question 15

What is a triple repeat?

Answer 15

When the sequence has a triplet and is repeated again and again.
ie CAG CAG CAG CAG
If repeated over thew normal threshold number of times= disease

Question 16

Give an example of a triplet expansion autosomal dominant disorder?

Answer 16

Huntington’s Disorder

Loss of neurones in basal ganglia and cortex of brain.

Question 17

What are the molecular mechanisms that causes Huntington’s disease?

Answer 17

Expansion of CAG repeat (more than 36 repeats) in exon 1 of Huntington’s gene results in polyglutamine tract within H protein

1) Aggregates form from the increased polyglutamine length, acting as inclusion bodies and toxins
2) Abnormal H protein reacts with transcription factors that affects gene expression.

Question 18

Which chain of haemoglobin is affected in sickle cell disease?

Answer 18

Beta globin chain

Question 19

How are sickle cells formed?

Answer 19

Both copies of B-globin gene is defective, low oxygen makes the globin clump to form a long rod shape that changes the cell shape to sickled.

Question 20

What is the genetic cause of cystic fibrosis?

Answer 20

A mutation (3 bp deletion) in the gene coding for Cystic Fibrosis Transmembrane Receptor protein which controls the pumping of chloride in and out of cells.

Question 21

What are the characteristics of a pedigree of X-linked disorder?

Answer 21

Inheritance is male->female->male

No male to male or female to female transmission.

Question 22

In Duchennes Syndrome, what happens to the dystrophin gene?

Answer 22

Mutation by triple repeat means the dystrophin gene produces defective dystrophin protein which can no longer effectively connect actin cytoskeleton with proteins in sarcolemma so there is muscle weakness and wasting of thigh muscles.

Question 23

What is the difference between Becker’s and Duchenne’s Syndrome genetically?

Answer 23

Becker’s disrupts the gene by deletion or duplication creating in frame changes whereas Duchenne’s mutates the gene by very large deletions creating out of frame changes.

Question 24

What is the genetic mechanism that causes Fragile X syndrome?

Answer 24

X linked so on the X chromosome there is mutation in the form of triple repeat of CGG in the FMRP gene. Leading to FMRP protein deficiency. More repeats = more severe mental retardation.

Question 25

How can these genetic disorders be genetically tested for and diagnosed?

Answer 25

Make primers for the gene that is affetced.
PCR them to create more copies of the gene.
Put in agarose gel electrophoresis.
Read off= if the bands are higher up the gel= more repeats of the gene so likely to be affected patient.
2 bands lower down the gel means the person is a carrier