Student Presentations Flashcards
Pfeiffer Syndrome gene family mutation
fibroblast growth factor receptor genes - FGFR-1 or FGFR-2
Which form of Pfeiffer Syndrome has milder symptoms?
Type 1 - mutation in FGFR-1
Which form of Pfeiffer Syndrome has worse symptoms?
Type 2 and 3 - mutation in FGFR-2
What does the mutation cause in Pfeiffer Syndrome?
prolonged signaling -> promotes early maturation of bone cells and premature fusion of bones in skulls, hands, feet
Most common mutations in CF?
deletions in CFTR gene that result in a missing aa in the protein
What does the mutation in CF cause?
protein can no longer locate the cell membrane -> complete loss of function as a Cl- ion transporter
What are two ways to detect CF?
multiplex allele-specific PCR and ss conformation polymorphism (SSCP)
multiplex allele-specific PCR for CF?
several pairs of primers anneal to differing target sequences - allows simultaneous analysis of multiple targets in a single sample (beneficial b/c CF caused by so many possible mutations)
SSCP (single strand conformation polymorphism) for CF?
conformational difference of ss nt sequence, due to mutations, allows gene sequences to be distinguished through gel electrophoresis, which separates the fragments according to their different conformations
What mutation causes sickle cell anemia?
Glu to Val at 6th position in beta subunit of Hb
What does the sickle cell anemia mutation cause?
causes Hb proteins to polymerize when no oxygen bound, inducing sickling of RBCs
Why are sickled RBC’s bad?
they damage endothelium by promoting adhesion of red and white blood cells to endothelial cells and can also damage the spleen
How is sickle cell anemia diagnosed?
HPLC or electrophoresis
HPLC diagnosis of sickle cell anemia
chromatography involving passing blood sample through column of solid absorbent material at a high pressure - allows for separation and ID of different alleles
electrophoresis diagnosis of sickle cell anemia
samples w/ sickle cell Hb alleles will have different migration patterns (won’t migrate as far) than WT Hb alleles
What is associated with late-onset Alzheimer’s?
ApoE4
What is most commonly associated with risk of Alzheimer’s?
AB42 form of amyloid precursor protein (APP)
What is the main mutation that causes spinal muscular dystrophy?
in SMN1 gene
What happens to the SMN2 gene in all people?
undergoes alternative splicing, resulting in 80-90% of mRNA’s produced being shorter than normal (missing exon 7 or 5)
How does shortened SMN2 mRNA contribute to spinal muscular dystrophy?
truncated SMN2 mRNA produced a non-functional SMN2 protein -> is not sufficient to overcome SMN1 mutation and sustain survival of motor neurons in the spinal cord
relationship b/w SMN2 copies and SMA disease phenotype
more SMN2 copies = milder disease phenotype
What is a potential method to reduce symptoms of SMA?
increase histone acetylation of SMN2 gene could promote increased expression of this gene - HDACIs being investigated as a means to treat SMA
What is the mutation that causes Fragile X Syndrome?
methylation of CpG islands and expansion of CGG repeats in FMR1 gene
What does the methylation result in in Fragile X?
- inability to cleave gene by Eag1 restriction enzyme
- expansion of CGG repeats -> larger fragments
Southern blot results from Fragile X?
affected males: one fragment > 5.2 kb
normal males: one 2.8 kb
carrier females: 2.8 kb + > 5.2 kb OR > 2.8 kb + 5.2 kb
normal females: 2.8 kb + 5.2 kb
How can you identify female carriers of Fragile X?
larger than usual fragments
What type of disease is Gaucher Disease?
lysosomal storage disease
What mutation causes Gaucher Disease?
defective beta-glucocerebrosidase
What does the mutation in Gaucher’s Disease cause?
reduced ability to hydrolyze the glycolipid glucocerebroside
How must functional glucocerebrosidase be expressed in vitro for drug therapy?
must be expressed in eukaryotic cells (Chinese hamster overy cells) b/c beta-glucocerebrosidase undergoes glycosylation (post-translational mod) normally
How is LHON inherited?
mitochondrial DNA - mother
