Genetic Enzyme Deficiencies Overview

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Questions and Answers

What is the primary enzyme affected in Lesch-Nyhan syndrome?

HexA

X-inactivation enzyme

HGPRT (correct)

N-acetylhexosaminidase B

How is Tay-Sachs disease inherited?

Autosomal recessive (correct)

Mitochondrial inheritance

Autosomal dominant

X-linked dominant

What is the result of the accumulation of unprocessed gangliosides in Tay-Sachs disease?

Increased energy production

Enhanced brain function

Normal brain development

Neuronal death and various clinical symptoms (correct)

What is a significant effect of sickle-cell anemia?

Formation of blocks in capillaries Signup and view all the answers

Which of the following conditions is characterized by self-mutilation behavior?

Lesch-Nyhan syndrome Signup and view all the answers

What type of disease is Tay-Sachs categorized as?

Lysosomal-storage disease Signup and view all the answers

What does HGPRT stand for?

Hypoxanthine-guanine phosphoribosyltransferase Signup and view all the answers

What is one of the pleiotropic effects of Lesch-Nyhan syndrome?

Kidney failure Signup and view all the answers

What characterizes the hemoglobin of individuals with the genotype βA/βS?

Half are normal and half are sickling form. Signup and view all the answers

What can cause sickle-cell symptoms in heterozygotes?

Sharp drop in oxygen content. Signup and view all the answers

What is the common basis for over 200 identified hemoglobin mutants?

Altered electrophoretic mobility due to amino acid substitutions. Signup and view all the answers

Which chromosome carries the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR)?

Chromosome 7. Signup and view all the answers

What is the primary effect of cystic fibrosis on the human body?

Abnormally viscous secreted mucus. Signup and view all the answers

What specific mutation is commonly associated with cystic fibrosis?

Deletion of a specific 3-bp region. Signup and view all the answers

What role does the CFTR protein play in the cell membrane?

Forms a chloride channel. Signup and view all the answers

Compared to sickle-cell anemia, what can be said about most other hemoglobin mutants identified?

Their effects are not as severe. Signup and view all the answers

Which protein structure alteration is a result of sickle-cell mutation?

It changes the structure of the β-polypeptide chain. Signup and view all the answers

What distinguishes heterozygous individuals with sickle-cell trait from those with sickle-cell anemia?

Heterozygous individuals have an equal mixture of both hemoglobin types. Signup and view all the answers

Which amino acid is present in the sixth position of the β-chain in sickle-cell hemoglobin?

Valine Signup and view all the answers

What happens to the β subunits in individuals with the genotype βS/βS?

They sickle at low oxygen tension. Signup and view all the answers

What is the relationship between the βA and βS alleles?

Both alleles are co-dominant. Signup and view all the answers

What condition is associated with sickle-cell anemia according to the results mentioned?

Increased blood viscosity Signup and view all the answers

What experiment did Linus Pauling and coworkers perform to analyze hemoglobin variants?

Electrophoresis Signup and view all the answers

What is the primary cause of Phenylketonuria (PKU)?

A mutation in the phenylalanine hydrolase gene Signup and view all the answers

What is the main impact of the mutation on hemoglobin structure due to the sickle-cell trait?

It alters the charge distribution in the protein. Signup and view all the answers

Which amino acid is converted by the phenylalanine hydrolase enzyme?

Tyrosine Signup and view all the answers

How does classic albinism primarily manifest in affected individuals?

White skin and hair with red eyes Signup and view all the answers

What kind of genetic mutation results in Lesch-Nyhan Syndrome?

Recessive mutation on the X chromosome Signup and view all the answers

What dietary management is recommended for individuals with PKU?

A diet providing just enough phenylalanine without excess Signup and view all the answers

What process is disrupted in individuals with classic albinism?

Conversion of tyrosine to DOPA in the melanin pathway Signup and view all the answers

What is a common symptom associated with excessive phenylalanine in PKU?

Cognitive impairment Signup and view all the answers

Which of the following statements about pleiotropy is correct in relation to PKU?

PKU has multiple effects resulting from both phenylalanine excess and tyrosine deficiency. Signup and view all the answers

What is the primary consequence of an abnormal CFTR protein in cystic fibrosis?

Prevented transport of chlorine ions Signup and view all the answers

What is the role of genetic counseling?

To provide unbiased information about genetic risks Signup and view all the answers

In a cross between two carrier parents, what is the probability that an offspring will inherit the disease?

1/4 Signup and view all the answers

Which method is NOT used for obtaining fetal cells in genetic analysis?

Ultrasound sampling Signup and view all the answers

Which aspect of genetic counseling relies heavily on examining family history?

Carrier detection Signup and view all the answers

What is typically true about a carrier of a recessive genetic mutation?

They are heterozygous for the mutation. Signup and view all the answers

What is the importance of assessing enzyme activity in fetal analysis?

To diagnose inherited diseases Signup and view all the answers

What type of genetic defect can genetic testing primarily detect?

Inherited enzyme and protein defects Signup and view all the answers

Study Notes

Genetically Based Enzyme Deficiencies in Humans

Single gene mutations are responsible for many human genetic diseases.
Some mutations result in a single, simple phenotype. Other mutations are pleiotropic. The presentation includes a table listing examples.

Enzyme Deficiencies in Humans

Several genetic disorders are linked to specific enzyme deficiencies.
A table in the presentation shows genetic defects, their associated locus, corresponding enzyme deficiency, and OMIM entry for various human genetic disorders.

Phenylketonuria (PKU)

PKU is caused by a mutation in the phenylalanine hydroxylase gene.
This prevents the conversion of phenylalanine into tyrosine.
Phenylalanine is an essential amino acid, but excess is harmful and normally converted to tyrosine.
PKU's effects are pleiotropic, arising from excess phenylalanine and the inability to produce tyrosine.
Diet is crucial in managing PKU, providing sufficient phenylalanine for protein synthesis without excess buildup.

Albinism

Classic albinism stems from an autosomal recessive mutation in the tyrosinase gene.
Tyrosinase converts tyrosine to DOPA, a crucial step in the melanin synthesis pathway.
Absence of melanin results in white skin, hair, and red eyes (lack of pigmentation in the iris).
Other forms of albinism exist due to defects in other genes involved in the melanin pathway.

Lesch-Nyhan Syndrome

Caused by a recessive mutation on the X chromosome in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene.
The disease primarily affects males, while heterozygous females may experience symptoms depending on X-inactivation patterns.
HGPRT is essential for purine utilization. Impaired HGPRT leads to purine accumulation and uric acid conversion.
Lesch-Nyhan syndrome exhibits pleiotropic effects, including uremia, kidney failure, mental deficiency, and self-mutilation.

Tay-Sachs Disease

A lysosomal storage disorder resulting from a recessive mutation in the hexA gene.
The hexA gene encodes the N-acetylhexosaminidase A (HexA) enzyme.
HexA cleaves a terminal N-acetylgalactosamine group from a brain ganglioside.
In affected individuals (homozygous recessive), the nonfunctional HexA enzyme causes unprocessed ganglioside buildup in brain cells, leading to various clinical symptoms.
The disease is incurable.

Gene Control of Protein Structure

Genes code for proteins that are not always enzymes.
Structural proteins, such as hemoglobin, are often abundant, making them easier to isolate and purify.

Sickle-Cell Anemia

First described by J. Herrick in 1910.
Sickled red blood cells (RBCs) change shape under low oxygen tension.
Sickled RBCs are fragile and block capillaries, causing tissue damage downstream.
The effects are pleiotropic, affecting extremities, heart, lungs, brain, kidneys, GI tract, muscles, joints, and resulting in heart failure, pneumonia, paralysis, kidney failure, and other symptoms.
Heterozygotes exhibit sickle cell trait, a milder form of the disease.
The disease is caused by a single mutant allele.

Hemoglobin Variants

Linus Pauling and coworkers (1949) used electrophoresis to show that hemoglobin from individuals with sickle-cell anemia (Hb-S) has altered mobility compared to normal hemoglobin (Hb-A).
Hemoglobin from individuals with sickle-cell trait shows equal amounts of Hb-A and Hb-S.
The sickle-cell mutation changes the form of the protein, illustrating that protein structure is controlled by genes.
Various hemoglobin mutants, with amino acid substitutions in the a and β chains, have been identified. Most effects are less severe than sickle-cell anemia.

Cystic Fibrosis

Cystic fibrosis (CF) mainly affects the pancreas, lungs, and digestive system.
Characterized by abnormally thick mucus secretions.
Managed with percussion and antibiotics.
Life expectancy is about 40 years.
The affected gene (chromosome 7) encodes the CFTR protein, a chloride channel in the cell membrane.
A deletion in the CF gene often leads to the deletion of an amino acid from this protein.

Genetic Counseling

Genetic testing detects inherited enzyme and protein defects, providing information about disease or carrier status.
Genetic counseling offers advice based on genetic assessments, focusing on probabilities of genetic defects and/or probabilities of prospective parents having a child with a genetic defect.
Pedigree analysis helps determine genetic inheritance from multiple generations.
Fetal analysis (amniocentesis and chorionic villus sampling) allows for examination of fetal cells (for protein levels, DNA changes and chromosomal abnormalities).

Carrier Detection

Carriers are heterozygous for a recessive gene mutation.
In crosses between two carriers, 1/4 of the offspring are expected to develop the disease and 1/2 will be carriers too.
Carrier phenotype is typically normal, but affected protein levels are often below normal levels.

Fetal Analysis

Genetic counseling considers whether a fetus is normal.
Fetal cell samples are necessary for this analysis.
Two methods are used: amniocentesis and chorionic villus sampling.
Fetal cells are cultured, and analyzed to assess protein or enzyme alterations, DNA changes, and chromosomal abnormalities.
Amniocentesis is more costly, and performed later (second trimester), while chorionic villus sampling is earlier but carries a higher risk for difficulties.

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Description

This quiz explores genetically based enzyme deficiencies in humans, focusing on conditions like Phenylketonuria (PKU) caused by specific gene mutations. It details the impact of these mutations on phenotypes and the role of diet in managing related disorders. Expect questions on examples, associated loci, and enzyme deficiencies.