Autosomal Recessive Flashcards
week 5 (48 cards)
What are the three main types of autosomal recessive disorders? What are the respective examples?
Cell metabolsim - PKU
Blood Cell function - Thalassemia, Sickle Cell, Haemochromatosis,
Membrane function- cystic fibrosis
What are compound heterozygotes?
individual with 2 different alleles (both defective)
severity depends on how much residual function is retained
Heterozygote advantage
relatively high frequency of disease-associated alleles causing reduced fitness for homozygotes = heterozygotes have a greater fitness
Features of autosomal recessive inheritance
single generation
parents and children of affeced = normally unaffected
male and female equally affected
parents = carriers
What is the recurrence risk for 2 carrier parents?
1/4
What is the chance that an unaffected sibling of affected individual is a carrier?
2/3
What is the impact of consanguineous marriage on autosomal recessive inheritance?
affected individuals seen in several generations.
What is gene therapy?
use of DNA as a pharmaceutical agent to treat lectures.
How does somatic cell gene therapy work?
replace defective genes in somatic cells so cells can produce the missing product or eliminate/ alleviate symptoms
What is germline gene therapy?
corrections are made to the germ cells such that inheritable genetic alterations are removed.
How can genes be introduced to somatic cells?
Mechanical (liposomes or microprojectiles) or Viral vectors
What are the 3 approaches to get genes to right site?
Ex vivo - target cell removed, cultured in lab, re-inserted
in situ- affected tissue directly exposed to therapy vector(not great for CF)
In Vivo- vector introduced t body, vector homes in on cells specifically designed for (best for CF)
How can an Autosomal receivve child be produced from parents with inly 1 carrier?
Germline mosaicism
de novo during embryogenesis
What is the affected gene and mutation for PKU?
Affected gene
- PAH gene
Mutation
-p.Arg408Trp
Clinical features of PKU including: early sympotims in 50% of untreated infants, nervous dysfunctions and common features of untreated individuals.
Early symptoms
-vomiting
-irritability
-eczema -like rash
-mousy urine odor
Nervous dysfunction
-increased muscle tone
-more active tendon reflexes
Untreated symptoms
-microcephaly
- widely spaced teeth
-prominent cheek and upper jaw bones
What is the screening test for PKU?
Heel prick test
Assess Phenylalanine (p) levels
Treatment of PKU?
Maintenance of blood P levels
Avoiding high-protein foods
Quality of life for PKU?
normal life and life span if following treatment
What gene is affected for a-thalassemia?
HBA1/2
What is the gene affted for b-thalassemia?
HBB
What is the phenotypic mechanism of a and b thalassemia?
incorrect or no synthesis of hemoglobin globin chains
a- a globin chain
b- b globin chain
What is the normal structure of hemoglobin and where are the genes located for a and b globin?
Normal: tetramer of 2-a-like and 2-b-like globin subunits. subunits change t fit needs of embryo, fetus and adult.
A: 4-a genes = 2 on each copy of Ch16
B: 2-b genes = 1 on each Ch11
What are the different types of a-thalassemia? Summarise each
silent
1 of 4 a mutated and asymptomatic
-minor
2 of 4 mutated = mild anaemia
-HbH
-3 of 4 mutated = mild -moderate anemia, enlarged spleen and jaundice
Hb Barts
-4 of 4 mutated = severe -excess fluid build up in developing baby = not survive after birth (usually
What are the different types of b-thalassemia? Summarise each
Minor
-1 of 2 mutated = lifelong mild anaemia
Intermediate
-2 of 2 mutated = mild/mod anameia, slow growth, symptoms early childhood or later
Major
2 of 2 = life-threatening anemia in first year, jaundice, enlarged spleen, bone changes and developmental delay.
