Molecular & Cytogenetics

Question 1

Cystic fibrosis - Demography

Answer 1

Most common in ashkenazi jews and caucasians, especially the delta-508 variant allele.

Screening kits are tailored towards these ethnic mutations, so residual risk after negative screen is actually highest in asian, black populations.

Question 2

mtDNA

Answer 2

Encoded on circular mitochondrial chromosome. All encode electron transport chain proteins, which are also contributed to by autosomal genes.

Diseases: Kearns-Sayre, Progressive External Ophthalmoplegia

Question 3

Primer design/selection

Answer 3

Length will determine degree of specificity.

Avoid too primers with high complementarity (will form primer dimers). Keep Tm similar.

Note complementary sequence; mutations must be accounted for (can select for them)

Question 4

Angelman, Prader-Willi

Answer 4

Angelman: Maternally expressed gene, so disease results from loss of maternal copy or paternal uniparental disomy.

Prader-Willi: Paternally expressed gene, so disease results from loss of paternal copy or maternal uniparental disomy.

Question 5

Pharmacogenomic targets of interest

Answer 5

CYP2C19 - Plavix (asians poor metabolizers)
CYP2D6 - Tamoxifen, Codeine
CYP2C9 - Warfarin (along with VKORC)
TPMT - Azathioprine

Question 6

Explanations for different karyotypes in POC analysis

Answer 6

Maternal contamination (common; 46,XX)
Twin pregnancies
Mosaicism (rare)

Question 7

Acrocentric chromosomes

Answer 7

13, 14, 15

21, 22

Question 8

Robertsonian translocation

Answer 8

Involves acrocentric chromosomes; creates a derivative/fused chromosome

Question 9

MDS cytogenetics

Answer 9

Good: -5, -20, -Y
Intermediate: +8
Bad: -7, -17, complex

Question 10

CNS tumor cytogenetics

Answer 10

Astrocytoma: Sometimes +7/-10
Oligodendroglioma: -1p/-19q (diagnostic)
Meningioma: -22 (think NF2)
Medulloblastoma: iso17q (diagnostic)