Lecture 3: Single Gene Disorders

Question 1

The location of a gene is the …. and the version of a given gene is an …..

Answer 1

The location of a gene is the LOCUS and the version of a given gene is an ALLELE.

• Some genes have several typical allele variations at one locus= Polymorphism (Ex. Eye Colour)

Question 2

What are two examples (one normal and one abnormal) of Hemizygosity in humans?

Answer 2

1) Males are Hemizygous for genes on the X chromosome

2) Females with Turner Syndrome are Hemizygous for the X chromosome genes too

Question 3

…. Disorders require only one allele to present their phenotype, while …. Disorders require both alleles to be present on both homologous chromosomes.

Answer 3

Autosomal Dominant; Autosomal Recessive

Question 4

True or False: Recessive Disorders tend to affect Enzymes, whereas Dominant Disorders tend to affect essential proteins.

Answer 4

True

Question 5

True or False: Recessive Disorders have a higher risk of reoccurrence than Dominant Disorders?

Answer 5

False: Autosomal Dominant Disorders have a higher risk of reoccurrence as they only require one allele to be passed on to offspring to elicit the phenotype

Question 6

What is an example of a 1) Autosomal Dominant Disorder 2) Autosomal Recessive Disorder

Answer 6

1) Familial Hypercholesterolemia

2) Albinism

Question 7

If an affected patients parents are both unaffected what must be true? If the patient has siblings what is the risk of reoccurrence in them?

Answer 7

The disorder must be Autosomal Recessive in nature and both parents must be carriers.
- There is a 2/3 risk of reoccurrence in siblings if one is affected

Question 8

True or False: A child with a rare dominant genetic disorder is more likely to have related parents (i.e. consanguinity)

Answer 8

False; A child with a rare RECESSIVE genetic disorder is more likely to have related parents (i.e. consanguinity)

Question 9

Familial Hypercholesterolemia (FH) is a …. Disorder due to a mutation in the …. receptor in Hepatocytes causing uncontrolled ….. Cholesterol production.

Answer 9

Familial Hypercholesterolemia (FH) is a AUTOSOMAL DOMINANT Disorder due to a mutation in the LDL receptor in Hepatocytes causing uncontrolled ENDOGENOUS Cholesterol production.

Question 10

Familial Hypercholesterolemia is an example of ….. as one copy of the …. gene on Chromosome 19 is not enough for proper function

Answer 10

Familial Hypercholesterolemia is an example of HAPLOINSUFFICIENCY as one copy of the LDLR gene on Chromosome 19 is not enough for proper function

Question 11

Homozygotes with Familial Hypercholesterolemia are better/worse as they have less/more normal LDL receptors

Answer 11

Homozygotes with Familial Hypercholesterolemia are WORSE as they have LESS normal LDL receptors

Question 12

Define Locus Heterogeneity?

Answer 12

Locus Heterogeneity= Same disease phenotype expressed by mutations of a variety of genes at different loci (Ex. Albinism)

Question 13

Albinism is a defect in …. metabolism due to a mutation in the …. enzyme

Answer 13

Albisinim is a defect in MELANIN metabolism due to a mutation in the TYROSINASE enzyme

• Recessive disorders affect enzymes typically

Question 14

FH is characterized by an …. in Plasma Cholesterol Levels and leads to an increase in …… risks.

Answer 14

FH is characterized by an INCREASE in Plasma Cholesterol Levels and leads to an increase in ARTHEROSCELROSIS/CORONARY HEART DISEASE risks.

Question 15

Why do rare Recessive Genetic Disorders arise from Consanguinity?

Answer 15

• There is an increased likelihood of parents being carriers of a rare recessive allele as they are part of the same family.
• This increases the chance of homozygosity of a rare recessive allele being presented to their offspring

Question 16

Is there a change in the chance of a child inheriting a rare Recessive Disorder from consanguineous parents?

Answer 16

No, although the chance of Hemizygosity of a rare Recessive allele is increased, the offspring still has a 1/4 chance of inheriting a rare Recessive Disorder from their consanguineous parents

Question 17

Name two disorders that significantly affect the Travelling Community of Ireland more compared to the average population…

Answer 17

1) Galactosemia (Inability to metabolize Galactose)

2) Hurlers Syndrome (Absence of Lysosomal Enzymes needed for GAGs Breakdown)

Question 18

What does the p and q stand for in the Hardy Weinberg Equation? (i.e. p + q = 1)

Answer 18

p= Dominant Allele
q= Recessive Allele

Question 19

What does p^2, 2pq and q^2 stand for in the Hardy Weinberg Equation? (i.e. p^2 + 2pq + q^2 = 1)

Answer 19

p^2= Homozygous Dominant Frequency
2pq= Heterozygous Frequency
q^2 = Homozygous Recessive Frequency

Question 20

True or False: Most Sex Linked Disorders are Y-Linked

Answer 20

False; Mose Sex Linked Disorders are X-Linked

Question 21

Name three X-Linked Disorders…

Answer 21

1) Duchenne Muscular Dystrophy (DMD)
2) Red-Green Colour Blindness
3) Hemophillia

Question 22

X-Inactivation/Lysonisation occurs during …. where either the maternal or paternal X is inactivated. This allows for …. between males and females

Answer 22

X-Inactivation/Lysonisation occurs during EMBRYOGENESIS where either the maternal or paternal X is inactivated. This allows for DOSAGE COMPENSATION between males and females

Question 23

True or False: Female Heterozygotes for X-Linked Mutations DO NOT demonstrate a phenotype, while affected males ALWAYS do.

Answer 23

True

Question 24

Carrier Females affect ….% of sons and ….% of Carrier daughters

Answer 24

Carrier Females affect 50% of sons and 50% of Carrier daughters
- All depends on which X is given to the offspring

Question 25

X- Linked Disorder affected males will transmit to ALL Daughters but NO sons

Answer 25

True

- Have to pass their affected X to their daughters but pass their normal Y to their sons