Student Presentations

Question 1

Pfeiffer Syndrome gene family mutation

Answer 1

fibroblast growth factor receptor genes - FGFR-1 or FGFR-2

Question 2

Which form of Pfeiffer Syndrome has milder symptoms?

Answer 2

Type 1 - mutation in FGFR-1

Question 3

Which form of Pfeiffer Syndrome has worse symptoms?

Answer 3

Type 2 and 3 - mutation in FGFR-2

Question 4

What does the mutation cause in Pfeiffer Syndrome?

Answer 4

prolonged signaling -> promotes early maturation of bone cells and premature fusion of bones in skulls, hands, feet

Question 5

Most common mutations in CF?

Answer 5

deletions in CFTR gene that result in a missing aa in the protein

Question 6

What does the mutation in CF cause?

Answer 6

protein can no longer locate the cell membrane -> complete loss of function as a Cl- ion transporter

Question 7

What are two ways to detect CF?

Answer 7

multiplex allele-specific PCR and ss conformation polymorphism (SSCP)

Question 8

multiplex allele-specific PCR for CF?

Answer 8

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)

Question 9

SSCP (single strand conformation polymorphism) for CF?

Answer 9

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

Question 10

What mutation causes sickle cell anemia?

Answer 10

Glu to Val at 6th position in beta subunit of Hb

Question 11

What does the sickle cell anemia mutation cause?

Answer 11

causes Hb proteins to polymerize when no oxygen bound, inducing sickling of RBCs

Question 12

Why are sickled RBC’s bad?

Answer 12

they damage endothelium by promoting adhesion of red and white blood cells to endothelial cells and can also damage the spleen

Question 13

How is sickle cell anemia diagnosed?

Answer 13

HPLC or electrophoresis

Question 14

HPLC diagnosis of sickle cell anemia

Answer 14

chromatography involving passing blood sample through column of solid absorbent material at a high pressure - allows for separation and ID of different alleles

Question 15

electrophoresis diagnosis of sickle cell anemia

Answer 15

samples w/ sickle cell Hb alleles will have different migration patterns (won’t migrate as far) than WT Hb alleles

Question 16

What is associated with late-onset Alzheimer’s?

Answer 16

ApoE4

Question 17

What is most commonly associated with risk of Alzheimer’s?

Answer 17

AB42 form of amyloid precursor protein (APP)

Question 18

What is the main mutation that causes spinal muscular dystrophy?

Answer 18

in SMN1 gene

Question 19

What happens to the SMN2 gene in all people?

Answer 19

undergoes alternative splicing, resulting in 80-90% of mRNA’s produced being shorter than normal (missing exon 7 or 5)

Question 20

How does shortened SMN2 mRNA contribute to spinal muscular dystrophy?

Answer 20

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

Question 21

relationship b/w SMN2 copies and SMA disease phenotype

Answer 21

more SMN2 copies = milder disease phenotype

Question 22

What is a potential method to reduce symptoms of SMA?

Answer 22

increase histone acetylation of SMN2 gene could promote increased expression of this gene - HDACIs being investigated as a means to treat SMA

Question 23

What is the mutation that causes Fragile X Syndrome?

Answer 23

methylation of CpG islands and expansion of CGG repeats in FMR1 gene

Question 24

What does the methylation result in in Fragile X?

Answer 24

• inability to cleave gene by Eag1 restriction enzyme

- expansion of CGG repeats -> larger fragments

Question 25

Southern blot results from Fragile X?

Answer 25

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

Question 26

How can you identify female carriers of Fragile X?

Answer 26

larger than usual fragments

Question 27

What type of disease is Gaucher Disease?

Answer 27

lysosomal storage disease

Question 28

What mutation causes Gaucher Disease?

Answer 28

defective beta-glucocerebrosidase

Question 29

What does the mutation in Gaucher’s Disease cause?

Answer 29

reduced ability to hydrolyze the glycolipid glucocerebroside

Question 30

How must functional glucocerebrosidase be expressed in vitro for drug therapy?

Answer 30

must be expressed in eukaryotic cells (Chinese hamster overy cells) b/c beta-glucocerebrosidase undergoes glycosylation (post-translational mod) normally

Question 31

How is LHON inherited?

Answer 31

mitochondrial DNA - mother