Typical and Atypical Mendelian inheritance

Question 1

What are the key features of autosomal dominant inheritance?

Answer 1

• Vertical pattern
• Male to male transmission
• Affects both male and females in equal proportions
• Can show incomplete or complete penetrance
• Variable expressivity
• Heterozygous

Question 2

What is the genetic basis of achondroplasia?

Answer 2

Mutations in FGFR3, causing short stature and short limbs.

Has complete penetrance

Question 3

What is variable expression?

Answer 3

A gene mutation which when inherited can result in varying severities of a disease in different individuals in the same family.

Question 4

Give an example of a disease showing variable expression

Answer 4

Neurofibromatosis.

Question 5

What are modifier genes?

Answer 5

Genes which alter the expressivity of an inherited condition e.g. neurofibromatosis

Question 6

What is complete and incomplete penetrance?

Answer 6

Inherited conditions with complete penetrance have a 100% chance of being present in an individual which inherits the mutated gene e.g. achondroplasia.

Inherited conditions with incomplete pentrance have an increased change of being present in an individual who inherits the gene e.g. BRCA1 mutation in breast cancer.

Question 7

What is gonadal mosaicism?

Answer 7

A mutation which occurs in the gamete cells and then passed onto offspring without being expressed in the parent’s phenotype.

Question 8

Give examples of autosomal dominant conditions

Answer 8

Inherited breast or colon cancer
ADPKD
NF1

Question 9

What are the key features of autosomal recessive inheritance?

Answer 9

• Horizontal pattern of inheritance e.g. siblings affected
• Males and females affected equally
• May be consanguinity
• Homozygous

Question 10

Give examples of autosomal recessive disorders.

Answer 10

Cystic fibrosis
PKU
Spinal muscular atrophy
CAH

Question 11

What are the key features of X linked recessive inheritance?

Answer 11

• Females less likely/more mildly affected than males.
• Knights move
• No male-male inheritance
• Females can be affected by skewed X inactivation by epigenetic modification
• All daughters are carriers from affected males.

Question 12

Give an example of X linked recessive inheritance

Answer 12

Duchenne muscular dystrophy

Question 13

What are the key features of X linked dominant inheritance?

Answer 13

• Vertical pattern of inheritance
• All daughters are affected from affected males.
• No male to male transmission
• Females are affected twice as much as males.

Question 14

Give examples of X linked dominant inheritance?

Answer 14

Vitamin D resistance rickets
Incontinentia pigmenti
Rett syndrome

Question 15

What is genetic anticipation?

Answer 15

A disease in which there is increasing severity and earlier onset in successive generations

Question 16

Give examples of inherited conditions which show genetic anticipation

Answer 16

Huntington’s disease
Fragile X syndrome
Myotonic dystrophy

Question 17

What is pseudo-dominant inheritance?

Answer 17

An autosomal recessive condition with a high carrier frequency, appearing autosomal dominant.

Question 18

Give an example of pseudo-dominant inheritance?

Answer 18

Gilbert’s syndrome

Question 19

What is mitochondrial inheritance?

Answer 19

Mitochondria contain their own DNA. Mitochondria are inherited from mothers, to varying extents

Question 20

Give examples of mitochondrial inheritance conditions?

Answer 20

Leigh’s disease.

Typically affect muscle, brain, eyes.

Question 21

What is heteroplasmy in mitochondrial inherited conditions?

Answer 21

A mother could pass on an egg with mostly mutated mitchondrial DNA which increases the risk of the child developing a mitochondrial disorder.

Question 22

What is the threshold effect in mitochondrial mutations?

Answer 22

A certain number of mutated mitochondria is needed to give rise to the disease.