Mendelian inheritance

Question 1

Alleles

Answer 1

Alternative forms of the same gene, which can be dominant or recessive. The phenotype reflects the dominant allele.

Question 2

Phenotype

Answer 2

The observable characteristics of an organism, determined by a combination of genes and the environment.

Question 3

Genotype

Answer 3

The genes possessed by an organism, inherited from the parents.

Question 4

Types of single gene disorders

Answer 4

• dominant
• recessive
• X-linked dominant/recessive
• mitochondrial inheritance

Question 5

Exceptions to Mendel’s rules in dominant inheritance

Answer 5

• variation in expression
• age-dependent penetrance
• new mutation
• anticipation
• mosaicism

Question 6

Dominant gene disorders

Answer 6

Heterozygotes with one copy of the altered gene have the condition. Most mutations cause loss of function of the allele, with the gene product being a structural protein or receptor.

Question 7

Marfan syndrome

Answer 7

An autosomal dominant disorder caused by a defective fibrillin gene, leading to connective tissue problems. Typical characteristics include being tall, abnormally long and slender limbs, fingers and toes, heart defects and lens dislocation. 75% of cases are inherited from one parent, while 25% arise from new mutation.

Question 8

Neurofibromatosis type 1

Answer 8

An autosomal dominant disorder caused by a defective neurofibromin gene, in which small, mainly benign tumours grow along the nerves. Symptoms include cafe au lait birthmarks, neurofibromas, patches of freckles and problems with the nervous system. Variation in expression may be seen between members of the same family.

Question 9

Variation in expression

Answer 9

Family members may show different signs of the same disease, possibly arising from other genes affecting the phenotype.

Question 10

Huntington’s disease

Answer 10

An autosomal dominant disorder that results in parts of the brain becoming damaged over time, causing a variety of neurological and psychological symptoms including involuntary movements, depression and dementia. HD shows age-related penetrance, as symptoms usually start between 30-50 years of age, and is usually fatal after a period of up to 20 years.

Question 11

Age-related penetrance

Answer 11

A delay in the onset of genetic disease.

Question 12

Achondroplasia

Answer 12

An autosomal dominant disorder caused by a defective FGFR3 gene, preventing the conversion of cartilage to bone. It is characterised by dwarfism, macrocephaly, small fingers and limited range of motion. 80% of cases are caused by a new mutation, although it can also be inherited.

Question 13

New mutation

Answer 13

A genetic disorder may arise from a new mutation in the gametes. The risk of new mutations increases with increasing paternal age, as the number of copying errors during the production of sperm by meiosis increases with the number of germ cell divisions.

Question 14

Myotonic dystrophy

Answer 14

An autosomal dominant disorder caused by a defective DMPK or CNBP gene, characterised by progressive muscle loss and weakness and impaired muscle contraction after relaxation (myotonia). The usual age of onset is 20-30s, although anticipation may lead to younger onset in successive generations.

Question 15

Anticipation

Answer 15

In successive generations, the age of onset is reduced and/or the severity of the phenotype is increased. May arise from the expansion of unstable trinucleotide repeat sequences, where the number of triplet repeats above the normal upper limit causes the disease.

Question 16

Severe osteogenesis imperfecta (brittle bone disease)

Answer 16

A genetic disorder affecting the development of the bones, often leading to multiple fractures. Mosaicism may be exhibited.

Question 17

Mosaicism

Answer 17

Where a single gene mutation/chromosomal anomaly occurs during mitosis after fertilisation, resulting in two populations of cells. If mosaicism occurs in the gonads it can be passed on to offspring.

Question 18

Recessive gene disorders

Answer 18

Homozygotes with two copies of the altered gene have the condition. Most mutations abolish the action of the allele, with the gene product being enzymes.

Question 19

Consanguinity

Answer 19

Reproduction between blood relatives increases the risk of two recessive alleles being passed on to offspring.

Question 20

Cystic fibrosis

Answer 20

An autosomal recessive condition, resulting in a build up of mucous in the lungs and GI tract.

Question 21

X-linked recessive gene disorders

Answer 21

Males with one copy of the altered gene on the X-chromosome (hemizygote) have the condition. Females with an altered gene on one copy of the X-chromosome pair (heterozygote) are carriers.

Question 22

X-linked recessive traits in females

Answer 22

Females may show X-linked recessive traits due to:

• skewed X-inactivation
• Turner syndrome (45, X)
• homozygous recessive
• X;autosome translocations

Question 23

Duchenne muscular dystrophy

Answer 23

An X-linked recessive condition, caused by a mutation to the dystrophin gene leading to progressive muscle weakness.

Question 24

X-linked dominant gene disorders

Answer 24

Heterozygotes/hemizygotes with one copy of the altered gene have the condition, resulting in an excess of affected females and no male to male transmission.

Question 25

Mitochondrial inheritance

Answer 25

An exclusively maternal pattern of inheritance, as only egg cells pass on their mitochondria to a fertilised zygote. Examples of disorders include Kearns-Sayre syndrome and MELAS.

Question 26

X-linked hypophosphomatemia

Answer 26

An X-linked dominant condition, also known as vitamin D resistant rickets, which can cause bone deformity.