Autosomal Recessive Lecture Objectives

Question 1

In an autosomal recessive disorder, we see a _________ pedigree

Answer 1

Horizontal (affected individuals are usually siblings)

Question 2

In PKU, there is high phenylalalnine and low tyrosine level in the plasma because the conversion from Phe to _________ is impaired

Answer 2

Tyrosine

Question 3

Most PKU cases are caused by defects in the ______ gene, encoding ___________, a liver enzyme that catalyzes the conversion of Phe to Tyr using cofactor BH4

Answer 3

PAH; phenylalanine hydroxylase

Question 4

A fraction of PKU patients have normal PAH but are defective in genes that are needed for the synthesis or regeneration of _________

Answer 4

BH4, the cofactor of PAH

Question 5

Most mutations in PAH are partial or complete _________

Answer 5

loss of function

Question 6

Alpha 1 Antitrypsin Defiency (ATD) patients have a 20 fold increased risk for developing ____________

Answer 6

emphysema

Question 7

ATD is a common genetic disorder among ___________

Answer 7

Northern European Caucasians

Question 8

Which enzyme is the primary target of alpha1-antitrypsin

Answer 8

SERPINA which targets elastase

Question 9

The _______ genotype have only 10-15% of normal alpha 1-AT activity

Answer 9

Z/Z

Question 10

The _______ genotype have 50-60% of normal alpha 1-AT activity and usually do not express disease symptoms.

Answer 10

S/S

Question 11

_____________ have 30-35% of normal alpha 1-AT activity and may develop emphysema

Answer 11

Z/S compound heterozygotes

Question 12

The Ashkenazi Jewish population is _________ at a higher risk for Tay Sach’s disease

Answer 12

100x

Question 13

Tay Sachs is a lysosomal storage disorder. It is the inability to degrade ______, which results in a 300 fold accumulation go sphingolipid inside swollen lysosomes in neurons in the CNS

Answer 13

Ganglioside

Question 14

The most common genetic defect causing Tay Sachs disease is caused by a ___________

Answer 14

Frameshift, which causes a premature stop codon

Question 15

Tay Sach’s disease is caused by a defective alpha subunit, where only Hex A is affected whereas Sandoff disease is caused by a ___________ and _________ activity are affected.

Answer 15

beta subunit, Hex A and Hex B

Question 16

In the AB variant form of Tay Sachs, the Hex A and Hex B are normal but Gm2 Ganglioside accumulates due to a defect in the ___________

Answer 16

Gm2 activator protein

Question 17

Testing for Tay Sach’s disease includes….

Answer 17

1. Screening (enzymatic activity assay) 2. Prenatal screening 3. DNA testing