Genetic Principles

Question 1

What are examples of conditions of autosomal dominant inheritance?

Answer 1

• Achondroplasia
• Breast/colon cancer
• APKD
• NF1
• HD

Question 2

Describe features of AD inheritance

Answer 2

• vertical transmission
• 1 copy of variant gene causes the condition
• phenotypic severity influenced by one or more modifier genes and environmental factors
• females and males equally affected

Question 3

Define variable expression

Answer 3

Individuals who are affected by the same condition but to different clinical degrees, even in the case of having the same gene variants and being in the same family (typical of AD conditions)

Question 4

Define incomplete penetrance

Answer 4

Inheritance of a gene variant by not being affected or less affected

Question 5

Define gonadal mosaicism and its impact on genetic disease

Answer 5

When some gonadal cells contain the mutated gene and others do not.

Increases the risk of a child inheriting a mutated gene from unaffected parents due to a new mutation arising.

Question 6

What are some examples of conditions which are autosomal recessive?

Answer 6

• CF
• Spinal muscular dystrophy
• Congenital adrenal hyperplasia
• Wilson’s disease
• Tay-Sachs disease

Question 7

Describe features of AR inheritance

Answer 7

• both parents of an affected individual are heterozygous carriers
• 2 copies of faulty gene inherited to be affected (homozygous)
• compound heterozygosity can cause disease (2 different pathogenic genes contained in the same gene)
• horizontal inheritance
• consanguinity and metabolic enzyme defects common
• males and females both equally affected

Question 8

Define revertant genes

Answer 8

When a variant gene regains normal functioning through further mutation

Question 9

What are some examples of X-linked recessive conditions?

Answer 9

• muscular dystrophy (BMD, DMD)

Question 10

Describe features of X-linked recessive conditions

Answer 10

• women typically unaffected due to other X-chromosome compensating
• no male-male transmission
• knight’s move transmission: skips over unaffected individuals

Question 11

Define manifesting carriers

Answer 11

When females are mildly affected by X-linked recessive conditions due to skewed X-inactivation where the mutated gene on the affected C-chromosome is kept switched on

Question 12

What are some examples of X-linked dominant inherited conditions?

Answer 12

• vitamin D resistant Rickets
• incontentia pigmenti
• Rett syndrome

Question 13

Describe features of X-linked dominant inheritance

Answer 13

• inherited by females (because sons will inherit their X only from their mother)
• 1 copy of faulty gene enough to cause phenotype (vertical transmission)
• no male-male transmission

Question 14

Define genetic anticipation

Answer 14

Increasing severity and earlier age of onset of a condition over successive generations

Question 15

What are examples of conditions affected by genetic anticipation?

Answer 15

• Fragile X
• HD
• myotonic dystrophy

Question 16

Describe features of mitochondrial inheritance

Answer 16

• inherited only from mother but to variable extents
• smaller genome

Question 17

Describe pseudo-dominant inheritance

Answer 17

• The appearance of autosomal dominant inheritance pedigree pattern (vertical transmission) when the condition is actually autosomal recessive
• occurs when there is high frequency of carriers or consanguinity
• eg. Gilbert Syndrome