Chapter 12 case studies and end of chapter questions
Case Studies
Case Study 1: Girl with JAK1 Mutation
Background: Girl born to healthy parents with an oozing rash, limb length discrepancies, and later developed vomiting and kidney issues.
Symptoms: Asthma, food allergies, overactive immune response.
Genetic Finding: Mutation in the JAK1 gene affecting enzyme activity for 25 cytokines.
Mutation Type: Missense (substitutes one amino acid for another).
Affected Areas: Mutation detected in some cells, leading to varied growth rates in skin and bones.
Treatment: Successful treatment with an autoimmune drug, health restored until death from COVID-19.
Descriptive Terms: De novo, gain-of-function, somatic.
Case Study 2: Jesse's Genetic Resistance
Background: Jesse, 86, lived with Eleanor during her COVID-19 illness but tested positive.
Hypothesis: Define three genes with variants that might have conferred protection against COVID-19.
SARS-CoV-2 Variants
Mutation Overview: Highly mutable virus with early variants named after detection countries.
Current Naming Convention: Alphanumeric codes to avoid stigmatization.
Vaccine Focus: Targeting viral spike protein, which has 1273 amino acids recognized by antibodies.
Impact of Mutations:
Affect viral replication, load, stability, transmissibility, infectivity.
Specific Mutations in the Spike Protein
Example Mutation: D614G
Change from aspartic acid (D) to glycine (G) at position 614.
Codon changes: GAU/GAC to GGU/GGC.
Amino Acids and Codon Table
Abbreviation and Codon References:
Alanine (Ala A): GCU, GCC, GCA, GCG
Arginine (Arg R): CGU, CGC, CGA, CGG, AGA, AGG
Other Abbreviations: Asparagine (N), Aspartic acid (D), Cysteine (C), etc.
Analysis Questions
Identify mutation types in variants.
point mutations, missens emutations, nonsense mutations, silent mutations, insertions and deletions
Describe E484A mutation: Mutation affecting the 484th position of the spike protein, altering amino acid related to virus characteristics.
Amino Acid Change Analysis:
E484A: Possible codon changes could occur in multiple ways.
L452R: Detail amino acid change and codon impacts.
Mutation Effects: UCA to UCG may have less impact vs. UCA to ACA due to similar characteristics of UCA codons.
Future Mutation Concept: Brainstorm a plausible future mutation.
The blue people of troublesome creek Kentucky
They had a mutation in the CYP5R3 gene that encoded for an enzyme that catalyzed a reaction with a type of hemoglobin with poor oxygen affinity into one with stronger oxygen affinity, resulting in the skin looking blue because the bloodstream carries too little oxygen.
Members with 1 mutation were slightly blue, 2 were more blue
The first genetic illness understood at the molecular level is sickle cell disease
In which valine replaces glutamic acid
Both sickle cell disease and thalassemia a result from abnormalities in the beta globin protein
Collagen formation 3 steps
three procollagen chains coil into a very regular triple helix, with glycine in the middle
enzymes snip off the ragged ends of the polypeptides, forming mature collagen
the collagen fibrils continue to associated with each other outside the cell, building networks that hold it together.
Sickle cell steps
valine changes the surface of hemoglobin molecules
the aggregated hoemoglobin molecules form ropelike cables that at first make red blood cells stick
red blood cells form sickles
the misshape cells lodge into vessells
sickling speeds up and spreads as oxygen level falls
great pain is felt in the blocked body parts
Hutchinson gilford progeria syndrome, muscular dystrophies and a heart disorder - genes associated, lamin A
