8 – Single Gene Disorders

Question 1

single gene disorders

Answer 1

caused by point mutations in single genes

Question 2

autosomal mode of inheritance

Answer 2

autosomal mode of inheritance

Question 3

recessive mode of inheritance

Answer 3

heterozygous parents are unaffected

- Complete loss of gene function leads to phenotype e.g. Cystic Fibrosis

Question 4

dominant mode of inheritance

Answer 4

• partial loss of gene function leads to phenotype

Question 5

autosomal recessive pedigree

Answer 5

• Males and females affected
• Disease absent from most generations
• Consanguinity (sexual relationship with a blood relative) increases frequency of affected individuals
• Carriers have 25% chance of having an affected child (Dd x Dd)

Question 6

cystc fibrosis

Answer 6

A disorder originating in secretory epithelial tissue
• Carrier frequency: 1 in ~25
• CF births: 1 in ~2500

Question 7

symptoms of cystic fibrosis

Answer 7

• Accumulation of mucus in lungs, pancreas, digestive tract and other organs.
• Multiple effects, including:
• chronic bronchitis
• recurrent bacterial infections

Question 8

What does CFTR do?

Answer 8

codes for a chloride channel

Regulates the flow of Cl- across the membrane

Question 9

how defect in CTFR causes CF

Answer 9

• Defect in Cl- transport causes extracellular mucus to become thicker and stickier
• Treatment: life is prolonged by antibiotics and by daily massage to clear mucus from airways

Question 10

how defect in CTFR causes CF

Answer 10

• Defect in Cl- transport causes extracellular mucus to become thicker and stickier
• Treatment: life is prolonged by antibiotics and by daily massage to clear mucus from airways

Question 11

precision medicine for CF

Answer 11

• Drugs to improve function of mutated protein

- Gene therapy treatments: to provide patients with a copy of the correct chloride channel.

Question 12

sickle cell anemia

Answer 12

a genetic disorder that causes abnormal hemoglobin, resulting in some red blood cells assuming an abnormal sickle shape

Question 13

symptoms of sickle cell anemia

Answer 13

anaemia
joint pain
swollen spleen
frequent severe infections

Question 14

treatment for sickle cell

Answer 14

regular blood transfusions

Question 15

molecular cause of SCA

Answer 15

• Caused by a mutation in the gene for β– chain of haemoglobin; leads to incorrect folding of the protein
• The defective haemoglobin forms long chains of rigid polymers (after O2 is released) which deform the red blood cell

Question 16

sickle cell trait

Answer 16

1. Carry one of the autosomal recessive genes

2. No symptoms

Question 17

heterozygote advantage

Answer 17

individuals who are heterozygous at a particular locus have greater fitness than do both kinds of homozygotes

Question 18

autosomal dominant pedigree

Answer 18

• Males and females affected
• Affected individuals have an affected parent
• 50% chance of affected parent having affected child

Question 19

Huntington’s disease

Answer 19

Genetic disorder that causes progressive deterioration of brain cells. caused by a dominant allele. symptoms do not appear until about the age of 30.

Question 20

Symptoms of Huntington’s Disease

Answer 20

• jerky movements
• personality changes
• deterioration of walking, speaking and swallowing abilities
• death will result from complications such as choking, infection or heart failure

Question 21

finding the HD gene

Answer 21

• Pedigree analysis of a Venezuelan family (14,000 members)
• Mapping of the HD gene
• Identification of the HD gene - encodes Huntingtin
• HD gene contains CAG repeats (encoding glutamine)
  11-34 repeats = normal
  36 - 125 repeats = Huntington Disease

Question 22

Familial Hypercholesterolemia

Answer 22

due to lack of low density lipoprotein (LDL) receptor

Question 23

symptoms of FH

Answer 23

• High levels of cholesterol in the blood from an early age
• Cholesterol deposits build up in joints
• Cardiovascular disease

Question 24

treatment for FH

Answer 24

• Cholesterol-lowering drugs e.g. statins

* Low cholesterol diet

Question 25

FH is an example of incomplete dominance

Answer 25

• Homozygotes (hh) have a 6-fold increase in blood cholesterol - heart attacks at age of 2
• Heterozygotes (Hh) have a 2-fold increase in blood cholesterol - heart attacks by age of 35

Dominant phenotype is caused by haploinsufficiency

Question 26

pedigree: sex-linked recessive

Answer 26

Females are carriers, mostly males affected - Carrier female will transmit to 50% of sons (affected) and to 50% of daughters (carriers)

• Affected male cannot transmit to sons but will transmit to 100% of daughters (carriers)

Question 27

Haemophilia

Answer 27

Genetic disease affecting the ability of the blood to clot

Question 28

Haemophilia symptoms

Answer 28

• Tendency to extensive bruising
• excessive bleeding
• Bleeding into joints causing crippling deformities

Question 29

Haemophilia treatment

Answer 29

intravenous Injections of factor 8

Question 30

haemophilia A

Answer 30

• Mutation in the gene for Factor VIII (on X chrom.)

- Incidence: 1 in 5,000 males

Question 31

haemophilia B

Answer 31

deficiency of factor IX

Question 32

Dystrophin

Answer 32

Links thin filaments to proteins of sarcolemma