Autosomal Recessive Disorders Flashcards
How do you calculate the carrier frequency from the disease frequency of an autosomal recessive trait?
Carrier frequency (2pq) is 1/2 the square root of the disease frequency (q^2) Ex: incidence is 1/3600, sqrt of 3600 = 60, 1/2 of 60 = 30. Carrier rate is 1/30
What are the basic characteristics and risks for autosomal recessive disorders?
Both parents are carriers
Only expressed in homozygous recessive genotype (rr)
Males and females equally affected
Horizontal inheritance pattern
Risk for unborn child = 1/4
Risk for siblings of affected to be carriers = 2/3 (RR, Rr, rR)
What is a “compound heterozygote”?
A person who carries two different mutant alleles for a trait.
How does beta globulin display compound heterozygosity?
B-globin gene has 100+ known alleles
Ba is wild type
Bs, Bc mutants for sickle cell and heme C diseases
A compound heterozygote would have Bs/Bc genotype
What two genes cause PKU?
PAH and BH4 (a cofactor) mutations
Over 400 known alleles
7 cause over 2/3 of PKU in Europeans
6 others cause over 80% of PKU in Asians
What age group must be screened for PKU and what test is conducted?
Newborns must be screened (usually in first week, but not too early)
Screening involves Mass Spectroscopy
How is PKU treated and what is the maternal effect?
Treatment: low-phenylalanine diet, Kuvan (for BH4), enzyme replace
Maternal effect: PKU positive women off of diet during pregnancy exposes unborn child to high levels of phe in circulation, high rates of miscarriage, malformations, and mental retardation
Alpha 1 Antitrypsin Deficiency. ATD
Disease occurence 1/2500, carrier frequency ~4%
Increased risk of emphysema, liver cirrhosis and liver cancer
Caused by decrease in SERPIN-A1 (SERine Protease INhibitor-A1)
Absence of SERPIN-A1 allows elastase to breakdown elastin in lung
Z-allele in SERPIN misfolds and accumulates in ER of liver cells
Tay-Sachs disease symptoms, age of onset, and consequences
Muscle weakness, excessive startle response
Loss of muscle control, seizure, mental retardation, vegetative state
Neurological deterioration beginning about 3-6 months of age
Results in death by 2-4 years.
What sort of disease is Tay-Sachs and what are the genes and substrates involved?
A lysosomal storage disease
Due to build up of Gm2-ganglioside (a glycolipid)
Defective Hexosaminidase-A, alpha & beta subunits
HexA mutations cause TS
HexB mutations cause Sandhoff disease (also lysosomal storage)
How is Tay-Sachs screened for?
Carrier screening in high risk populations
Prenatal diagnosis if both parents are carriers
Enzymatic activity test
DNA test
