Autosomal Recessive Disorders

Question 1

four consequences of having multiple allels at a locus

Answer 1

no phenotypic effect

contribute to normal variation of a specific trait

affect disease susceptibility

directly disturbe protien function and cause a monogenic disease

Question 2

describe the distribution of a carrier vs. non-carrier trait

Answer 2

can use this to determine the probability that one is a carrier

Question 3

What are some ways that mutations can alter proteins?

Answer 3

primary peptide structure

peptide folding/coiling

subunit assembly

association with other proteins

protein stability

intracellular transport

targetting/packaging in organelles

active site

regulatory sites

Question 4

consequences of enzyme deficiency

Answer 4

accumulation of substrate A

deficiency of product B

accumulation of alternate product E

Question 5

Tay-Sachs disease

Answer 5

macular cherry red spot caused by lysosomal storage of the substrage ganglioside GM2 in neurons

neurologic deterioration in 3-6 months, primarily affects Ashkenazi Jews

caused by deficiency of hexosaminidase A through a mutation of the HEXA gene/alpha subunit

Question 6

consequences of substrate accumulation

Answer 6

stored in lysosomes or cytoplasm

diffused across cell and tissue compartments

excreted in the urine

Question 7

GM2 catabolism

Answer 7

the proper way to process GM2 is the removal of GalNAc

Question 8

hexosaminidase formation and function

Answer 8

Question 9

hexosaminidase status of Tay-Sachs

Answer 9

A is absent B is present, and cleavage of GM2 is absent

Question 10

hexosaminidase status of Sandhoff

Answer 10

both A and B are absent, and cleavage of GM2 is absent

Question 11

AB variant

Answer 11

both hexosaminidase A and B are present, but the activator is missing, so the GM2 still cannot be cleaved

Question 12

symptoms of mucopolysaccharidosis I

Answer 12

joint contractures, joint stiffness, dystosis multiplex, visceromegaly, coarse faces, corneal clouding

Question 13

mucopolysaccharidoses

Answer 13

a group of 10 or more disorders which are characterized by defective lysosomal degradation of glycosaminoglycans, and this accumulation is damaging ot tissues

Question 14

genetic heterogeneity

Answer 14

when similar phenotypes are generated by many different enzymes or different mutations of the same enzyme

Question 15

locus heterogeneity

Answer 15

when very similar phenotypes are caused by deficiencies in different enzymes

Question 16

allelic heterogeneity

Answer 16

when dissimilar phenotypes are caused by the same allelic mutations

Question 17

Describe the work of Fratantonia nd Neufeld that letd to a way for the reliable diagnosis of different mucopolysaccharidosis.

Answer 17

used radiolabeled sulfur in patients and then grew different cell lines together

found that two cells with different enzyme deficiencies could complement each other and rescue the phenotype

Question 18

Which variants of mucopolysaccharidosis demonstrate allelic heterogeneity?

Answer 18

Type I (Hurler and Scheie) and Type II (Hunter)

Question 19

Which variants of mucoplysaccharidosis demonstrate locus heterogeneity?

Answer 19

type III (Sanfilippo) and Type IV (Marquio)

Question 20

four sources of variation in genetically determined traits

Answer 20

locus heterogeneity, alleic heterogeneity, epistasis, environment

Question 21

I-cell disease

Answer 21

results from deficiency of UDP-N-acetylglucosamine transferase, leading to a lack of the mannose-6-phosphate recognition marker, so enzymes don’t make it to the lysosome

similar phenotypes to Hurler Syndrome

Question 22

glycogen storage diseases

Answer 22

a group of diseases that result in both deficiency of product and accumulation of substrate

most common is the glucose-6-phosphatase deficiency, so children become hypoglycemic during fasting

Question 23

urea cycle disorders

Answer 23

results in accumulation of substrate and deficiency of product, but they are not considered storage diseases because the substrates are not stored

disease arise from the accumulation of ammonia

treatment involves reduction of protein intake or the utilizatino of alternate metabolic routes for detoxification (ex. supplementing with arginine for a arginosuccinic acid to arginine block)

Question 24

propionic acidemia

Answer 24

a deficiency of propionyl-CoA carboxylase results in accumulation of substrate and also accumulation of alternate substrate

the build-up of several acidic molecules may cause acidosis and damage to the CNS

Question 25

multiple carboxylase deficiency

Answer 25

an example of product deficiency causing disease

a defect in the biotinidase enzyme prevents biotin recycling and apocarboxylases are unable to become holocarboxylases

acumulation of ketones and lactic acid can cuase several growth defects and disease symptoms

supplementation with biotin in the diet is an effective treatment

Question 26

galactosemia

Answer 26

results from the deficiency of Gal-1-P uridyl transferase

causes disease through substrate accumulation and an abnormal metabolite

conversion of accumulated galactose to galactitol also causes cataracts