8 – Single Gene Disorders Flashcards
single gene disorders
caused by point mutations in single genes
autosomal mode of inheritance
autosomal mode of inheritance
recessive mode of inheritance
heterozygous parents are unaffected
- Complete loss of gene function leads to phenotype e.g. Cystic Fibrosis
dominant mode of inheritance
- partial loss of gene function leads to phenotype
autosomal recessive pedigree
- 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)
cystc fibrosis
A disorder originating in secretory epithelial tissue
• Carrier frequency: 1 in ~25
• CF births: 1 in ~2500
symptoms of cystic fibrosis
- Accumulation of mucus in lungs, pancreas, digestive tract and other organs.
- Multiple effects, including:
- chronic bronchitis
- recurrent bacterial infections
What does CFTR do?
codes for a chloride channel
Regulates the flow of Cl- across the membrane
how defect in CTFR causes CF
- 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
how defect in CTFR causes CF
- 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
precision medicine for CF
- Drugs to improve function of mutated protein
- Gene therapy treatments: to provide patients with a copy of the correct chloride channel.
sickle cell anemia
a genetic disorder that causes abnormal hemoglobin, resulting in some red blood cells assuming an abnormal sickle shape
symptoms of sickle cell anemia
anaemia
joint pain
swollen spleen
frequent severe infections
treatment for sickle cell
regular blood transfusions
molecular cause of SCA
- 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
sickle cell trait
- Carry one of the autosomal recessive genes
2. No symptoms
heterozygote advantage
individuals who are heterozygous at a particular locus have greater fitness than do both kinds of homozygotes
autosomal dominant pedigree
- Males and females affected
- Affected individuals have an affected parent
- 50% chance of affected parent having affected child
Huntington’s disease
Genetic disorder that causes progressive deterioration of brain cells. caused by a dominant allele. symptoms do not appear until about the age of 30.
Symptoms of Huntington’s Disease
- jerky movements
- personality changes
- deterioration of walking, speaking and swallowing abilities
- death will result from complications such as choking, infection or heart failure
finding the HD gene
- 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
Familial Hypercholesterolemia
due to lack of low density lipoprotein (LDL) receptor
symptoms of FH
- High levels of cholesterol in the blood from an early age
- Cholesterol deposits build up in joints
- Cardiovascular disease
treatment for FH
- Cholesterol-lowering drugs e.g. statins
* Low cholesterol diet
FH is an example of incomplete dominance
- 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
pedigree: sex-linked recessive
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)
Haemophilia
Genetic disease affecting the ability of the blood to clot
Haemophilia symptoms
- Tendency to extensive bruising
- excessive bleeding
- Bleeding into joints causing crippling deformities
Haemophilia treatment
intravenous Injections of factor 8
haemophilia A
- Mutation in the gene for Factor VIII (on X chrom.)
- Incidence: 1 in 5,000 males
haemophilia B
deficiency of factor IX
Dystrophin
Links thin filaments to proteins of sarcolemma
