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Flashcards in Autosomal Recessive Disorders Deck (26):

four consequences of having multiple allels at a locus

no phenotypic effect

contribute to normal variation of a specific trait

affect disease susceptibility

directly disturbe protien function and cause a monogenic disease


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

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


What are some ways that mutations can alter proteins?

primary peptide structure

peptide folding/coiling

subunit assembly

association with other proteins

protein stability

intracellular transport

targetting/packaging in organelles

active site

regulatory sites


consequences of enzyme deficiency

accumulation of substrate A

deficiency of product B

accumulation of alternate product E


Tay-Sachs disease

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


consequences of substrate accumulation

stored in lysosomes or cytoplasm

diffused across cell and tissue compartments

excreted in the urine


GM2 catabolism

the proper way to process GM2 is the removal of GalNAc


hexosaminidase formation and function


hexosaminidase status of Tay-Sachs

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


hexosaminidase status of Sandhoff

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


AB variant

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


symptoms of mucopolysaccharidosis I

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



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


genetic heterogeneity

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


locus heterogeneity

when very similar phenotypes are caused by deficiencies in different enzymes


allelic heterogeneity

when dissimilar phenotypes are caused by the same allelic mutations


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

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


Which variants of mucopolysaccharidosis demonstrate allelic heterogeneity?

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


Which variants of mucoplysaccharidosis demonstrate locus heterogeneity?

type III (Sanfilippo) and Type IV (Marquio)


four sources of variation in genetically determined traits

locus heterogeneity, alleic heterogeneity, epistasis, environment


I-cell disease

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


glycogen storage diseases

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


urea cycle disorders

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)


propionic acidemia

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


multiple carboxylase deficiency

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



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