Single Gene & Multifactorial Disorders

Question 1

What is an allele?

Answer 1

One of two or more alternative forms of a gene

Question 2

What is the genotype?

Answer 2

Genetic constitution of an organism

Question 3

What is the phenotype?

Answer 3

Observable properties of an organism produced by a combination of genotype and environment

Question 4

What is a mutation?

Answer 4

Alteration in DNA or chromosome sequence or structure

Question 5

What is a point mutation?

Answer 5

Single base substitution, deletion or insertion

Question 6

What is a synonymous substitution?

Answer 6

Point mutation resulting in the same amino acid being coded for

Question 7

What is a mis-sense substitution?

Answer 7

Point mutation resulting in a different amino acid being coded for

Question 8

What is a nonsense substitution?

Answer 8

Point mutation resulting in a premature stop codon

Question 9

What is a frame shift?

Answer 9

Deletions/inversions of bases which are not a multiple of 3

Affects the way in which every following codon is read

Question 10

How can mutations in the non-coding region of a gene have effects?

Answer 10

Alter levels of expression in gene if occurring in regulatory regions

Question 11

What is the difference between Becker muscular dystrophy and Duchenne muscular dystrophy?

Answer 11

Becker - mutation in dystrophin gene promoter; normal dystrophin at reduced levels

Duchenne - mutation in dystrophin coding region; faulty dystrophin

Question 12

What causes phenylketonuria?

Answer 12

Recessive mutation of phenylalanine hydroxylase gene

Question 13

Does phenylketonuria affect everyone with the mutation?

Answer 13

No only homozygotes

Question 14

What does phenylalanine hydroxylase do?

Answer 14

Converts phenylalanine into tyrosine

Question 15

What are the effects of too much phenylalanine?

Answer 15

Too much = toxic to brain

Severe mental retardation, slow growth

Early death

Question 16

How is phenylketonuria managed?

Answer 16

Low phenylalanine in diet

Question 17

What does tyrosinase do?

Answer 17

Converts tyrosine into melanin

Question 18

Is oculocutaneous albinism dominant or recessive and why?

Answer 18

Recessive

Normal allele of tyrosinase is dominant over mutant allele

Question 19

What effect does a haploinsufficient dominant allele have in a heterozygote?

Answer 19

Individual produces 50% of normal level of gene product but this is insufficient for gene function

Question 20

What is an example of a syndrome caused by a haploinsufficient dominant allele?

Answer 20

Waardenburg syndrome type 1

Question 21

What is Waardenburg syndrome type 1?

Answer 21

Haploinsufficient dominant allele of Pax3 = not enough Pax3

Affects movement of neural crest cells causing developmental abnormalities

Hereditary deafness and pigmentation abnormality

Question 22

In a pedigree chart, what does a square represent?

Answer 22

Male

Question 23

In a pedigree chart, what does a circle represent?

Answer 23

Female

Question 24

In a pedigree chart, what does a filled-in shape represent?

Answer 24

Affected individual

Question 25

In a pedigree chart, what does a shape with a dot represent?

Answer 25

Carrier

Question 26

How are the individuals in a pedigree chart labelled?

Answer 26

Roman numerals denote generation Normal numbers denote individuals from left to right

Question 27

Give two examples of disorders which show autosomal recessive inheritance.

Answer 27

Phenylketonuria Oculocutaneous albinism

Question 28

What are the features of an autosomal recessive pedigree chart?

Answer 28

Unaffected parents give rise to an affected individual Affected includes males and females

Question 29

What type of inheritance is achondroplasia likely to show?

Answer 29

Autosomal dominant

Question 30

Describe achondroplasia.

Answer 30

Short-limbed dwarfism, normal intelligence and lifespan Caused by mutation in gene for a growth factor receptor (Gly to Arg commonly) Homozygous = lethal

Question 31

What is an example of X-linked recessive inheritance?

Answer 31

Haemophilia A

Question 32

What is haemophilia A caused by?

Answer 32

Mutation in gene for blood clotting factor VIII on X chromosome

Question 33

What are the features of a pedigree chart showing X-linked recessive inheritance?

Answer 33

Occurs more frequently in males Cannot be passed father to son All daughters of an affected father are carriers

Question 34

What are multifactorial disorders?

Answer 34

Arise from action of 2 or more genes and interaction between genes and the environment Show continuous variation

Question 35

What are polymorphisms?

Answer 35

Mutations which are common in the population Contribute to susceptibility to complex, multifactorial disorders

Question 36

Which genes increase susceptibility for type 1 diabetes?

Answer 36

HLA (human leukocyte antigen) genes

Question 37

Which genes increase susceptibility for type 2 diabetes?

Answer 37

Genes involved in glucose metabolism or adipose tissue development

Question 38

What is the effect of a dominant negative allele on a heterozygote?

Answer 38

Mutant allele results in nonfunctional oligomers as well as normal ones Results in nonfunctional enzyme/protein

Question 39

Give an example of a gene which is commonly affected by a dominant negative allele?

Answer 39

Mitochondrial aldehyde dehydrogenase Glu to Lys missense substitution (position 487)