Mendelian Inheritance of Disease

Question 1

Chromosome

Answer 1

Linear DNA molecule

Question 2

Gene

Answer 2

Length of DNA which encodes a particular protein

Question 3

Locus

Answer 3

Genes are arranged along a chromosome in a linear order.

Each gene has a precise location.

Question 4

Allele

Answer 4

Alternative forms of a gene

Each chromosome bears only a single allele at a given locus.

Question 5

Describe chromosomes in females

Answer 5

2 x 22 pairs

AND

XX

Question 6

Describe chromosomes in males

Answer 6

2 x 22 pairs

AND

XY

Question 7

Homozygous

Answer 7

The same genetic variants (alleles)

Question 8

Heterozygous

Answer 8

Different alleles

Question 9

What is a genetic disease ?

Answer 9

One caused by a change in genes

Question 10

State some genetic disease causes

Answer 10

Chromosome aneuploidies (extra or missing chromosome)

More subtle chromosome abnormality
Extra piece of chromosome
Missing piece of chromosome

Change in gene sequence:
- Insertion or Deletion of a few bases
- Change of a single base where it matters

Question 11

Where does a mutation have its effect ?

Answer 11

DNA gene sequence:
- Promoter region
- Exon –> causes defect in protein
- Intron –> causes splicing defects

Question 12

Promoter and splice site sequence changes:

Answer 12

STOP transcription or can cause abnormal splicing

Question 13

Base change causing an amino acid change:

Answer 13

Change in protein sequence
Not every base change causes disease
This may or may not reduce protein function

Some missense mutations make a protein work faster

Question 14

Insertion or deletion of bases:

Answer 14

3 base pairs encode 1 amino acid

Mutations may be ‘in frame’ OR ‘out of frame’

Question 15

Trinucleotide repeat expansions:

Answer 15

Replication of a tri-nucleotide (series of 3 base pairs)

Question 16

Types of mutations in DNA sequences

Answer 16

STOP
Missense
Insertion
Deletion - out of frame
Deletion - in frame
Triplet expansion

Question 17

Disorders with mendelian inheritance

Answer 17

A change in a single gene, sufficient to cause clinical disease, is inherited in a fashion predicted by Mendel’s laws.

Question 18

Non-Mendelian inheritance

Answer 18

Everything else including common multifactorial diseases.

Question 19

Methods of inheriting mutations

Answer 19

Autosomal dominant
Autosomal recessive
X-linked
(Mitochondrial)

Question 20

Autosomal dominant

Answer 20

1 fault copy of gene causes disease

Diseases seen in all generations

50% risk of affected children if parent is affected

Males and females are equally likely to be affected.

Question 21

Autosomal Dominant disease

Answer 21

Marfan’s syndrome
- caused by mutation in fibrillin 1

Question 22

Causes of Marfan’s syndrome

Answer 22

(>1300 identified mutations)

25% arise from new mutations

75% inherited in Autosomal Dominant pattern

1 in 5000

Question 23

Feature of Marfan’s syndrome

What is its effect on the body ?

Answer 23

Dilation of aorta

Question 24

Allelic heterogeneity

Answer 24

Different mutations in the same gene can cause the same disease.

This is due to loss of gene function.

Question 25

Example of allelic heterogeneity

Answer 25

Marfan’s syndrome

Question 26

Example of locus heterogeneity

Answer 26

HHT1
A point mutation in the endoglin gene on chromosome 9

HHT2
Same phenotype, but different gene

Question 27

Locus heterogeneity

Answer 27

The same disease might be caused by mutations in one of several genes.

To do a gene test, you need to know approximately where to look.

Question 28

Autosomal recessive criteria to cause disease

Answer 28

2 faulty copies of gene to cause the disease

Question 29

Features of autosomal recessive mutations

Answer 29

Often only one generation affected

1 in 4 risk of an affected child if carriers

Increased likelihood in consanguineous families.

Question 30

Example of an autosomal recessive disease

Answer 30

Sickle cell anaemia

Question 31

X linked recessive features

Answer 31

In terms of disease genes, the Y chromosome is almost irrelevant.

X chromosome has lots of genes.
The gene fault lies on the X chromosome.

Question 32

X-linked diseases

Answer 32

Dystrophin
Haemophilia

Question 33

Duchenne Muscular Dystrophy

Answer 33

• Mild developmental delay
• Slow to walk
• Difficulty standing
• Unable to run

On examination
- Hypertrophy of calf muscles
- Proximal muscle weakness

Creatine Kinase 10,000iu

Question 34

Muscle biopsy of muscular dystrophy patient

Answer 34

If you don’t have dystrophin, you damage your muscle fibres at every contraction / relaxation.

Muscle tissue tries to compensate by growing more muscle tissue.

This doesn’t work.

Question 35

X-linked recessive inheritance

Answer 35

For a female carrier:
- 1/2 of the male children of a carrier will be affected
- 1/2 of the female children will be carriers

If an affected male has children:
- All of male children will be normal
- All of female children will be carriers

Question 36

Describe a female carrier of DMD

Answer 36

A female carriers a mutation but will not show major features of disease

Question 37

Nonpenetrance

Answer 37

Failure of a genotype to manifest

Question 38

Variable expression

Answer 38

Different family members may show different features of a disorder

Question 39

What causes complications to basic pedigree patterns ?

Answer 39

Due to influence of other genes and environment, as well as chance.

Question 40

Where else can you find DNA ?

Answer 40

Mitochondrial DNA

Question 41

Describe Mitochondrial DNA

Answer 41

16,559 base pairs

Many copies (because of many mitochondria) in a cell

Question 42

What does mitochondria DNA contain ?

Answer 42

Contains important genes for mitochondrial metabolic pathways and ribosomal RNAs.

Question 43

Where is mRNA inherited from ?

Answer 43

Inherited almost exclusively maternally.

Point mutations and deletions occur.

Question 44

Key features of mitochondrial inheritance

Answer 44

Rare
Maternal Transmission only

Sons and Daughters equally affected