Genetic Mutations and Associated Diseases

Questions and Answers

What type of mutation can cause a disease through insufficiency of the haploid genome?

Complete dominance

Dominant-negative mutations

Haploinsufficiency (correct)

Codominance

In which condition does a mutated protein product interfere with normal protein function?

Dominant-negative mutation (correct)

Aberrant dominance

Incomplete dominance

Haploinsufficiency

Which of the following best exemplifies codominance in human genetics?

Individuals with type O blood

Individuals with sickle cell anemia

Individuals with hemophilia

Individuals with type AB blood (correct)

What determines the blood group of an individual concerning the ABO blood group system?

Two alleles at the same gene locus Signup and view all the answers

What is the result of a mutation in the FGFR3 gene in the context of achondroplasia?

Inhibition of chondrogenesis Signup and view all the answers

Which blood group results from the homozygous IA/IA genotype?

Blood group A Signup and view all the answers

How does complete dominance differ from codominance in terms of genotype representation?

Homozygotes and heterozygotes appear the same Signup and view all the answers

What is the primary role of the dystrophin protein in muscle cells?

It anchors the actin cytoskeleton to the extracellular matrix. Signup and view all the answers

How do female carriers of X-linked recessive disorders typically present clinically?

They exhibit mild to no symptoms but could occasionally have severe manifestations. Signup and view all the answers

What is the consequence of a loss-of-function mutation in the dystrophin gene?

Progressive death of muscle fibers starting from limbs. Signup and view all the answers

What distinguishes Duchenne muscular dystrophy from Becker's muscular dystrophy?

Duchenne involves complete loss of dystrophin function while Becker retains partial function. Signup and view all the answers

How does the random X chromosome inactivation in females impact inheritance patterns?

It creates a mosaic of normal and affected cells depending on which X is inactivated. Signup and view all the answers

What is the characteristic of a haplosufficient gene concerning the phenotype it governs?

It requires only one functional allele to ensure a normal phenotype. Signup and view all the answers

What is phenylketonuria primarily caused by?

Failure to convert phenylalanine to tyrosine. Signup and view all the answers

Which of the following is NOT a consequence of cystic fibrosis?

Reduced cholesterol levels. Signup and view all the answers

How does the CFTR gene mutation contribute to the symptoms of cystic fibrosis?

By disrupting ion balance in epithelial cells. Signup and view all the answers

In the context of phenocopies, what does this term imply?

Identical phenotypes arise from different genetic mutations. Signup and view all the answers

Which statement about males carrying X-linked recessive diseases is true?

They are typically affected due to having only one X chromosome. Signup and view all the answers

What is the role of tetrahydrobiopterin (THB) in some cases of phenylketonuria?

It serves as a co-factor for phenylalanine hydroxylase. Signup and view all the answers

What is the significance of the delF508 mutation in cystic fibrosis?

It is the most common mutation associated with cystic fibrosis in Europe. Signup and view all the answers

What is an example of a selective advantage for heterozygotes carrying mutations in cystic fibrosis?

Increased resistance to typhoid fever. Signup and view all the answers

What determines whether a trait is expressed in homozygotes for recessive diseases?

The complete absence of protein function. Signup and view all the answers

What is the genotype of a healthy carrier of sickle cell anemia?

HbA/HbS Signup and view all the answers

Which of the following describes a characteristic of the O blood group?

Presence of H antigen only Signup and view all the answers

In the context of sickle cell anemia, how does dominance function at the organismal level for the heterozygote?

Complete dominance of the HbA allele is observed. Signup and view all the answers

What does non-penetrance imply in the context of hereditary diseases?

Some individuals with the mutation do not show symptoms. Signup and view all the answers

What is the main reason for the appearance of recessive diseases in the offspring of healthy parents?

Consanguinity increasing recessive genotype chances Signup and view all the answers

What type of mutation characterizes the sickle cell anemia condition at a molecular level?

Missense mutation Signup and view all the answers

Which condition is characterized by variable expression of a genetic trait?

Neurofibromatosis Signup and view all the answers

During which observation level does codominance occur with respect to sickle cell anemia?

Molecular level Signup and view all the answers

What is typically indicated by the presence of partially colored symbols in a family tree representing genetic traits?

Variable expression of symptoms Signup and view all the answers

In reciprocal crosses involving red and white eyes, why do males only exhibit white eyes when the white-eyed female is crossed with a red-eyed male?

Males have only one X chromosome which carries the white allele. Signup and view all the answers

What conclusion can be drawn from the inheritance patterns observed in the F2 generation regarding the red and white eye phenotypes?

Red eyes show variable expression depending on parental genotype. Signup and view all the answers

In the case of testicular feminization syndrome, which genetic component is crucial for developing male secondary sexual characteristics?

Functionality of the SRY gene. Signup and view all the answers

How does the inheritance pattern of hemophilia differ in female carriers compared to affected males?

Daughters of affected males are always carriers but not affected. Signup and view all the answers

What type of vision is characterized by the inability to distinguish red from green colors?

Deuteranopia. Signup and view all the answers

What is a characteristic feature of monochromacy?

Complete inability to perceive colors. Signup and view all the answers

In the context of hemophilia, what type of gene mutation is primarily implicated in this disorder?

X-linked recessive mutation. Signup and view all the answers

What was a significant historical consequence of Queen Victoria being a carrier of hemophilia?

The condition spread into several royal families across Europe. Signup and view all the answers

What does the presence of a Barr body in female cells indicate?

One of the X chromosomes is inactivated. Signup and view all the answers

Why have sex chromosomes been retained throughout evolution?

To facilitate specific embryonic development processes. Signup and view all the answers

What mechanism leads to dominant-negative mutations, and how does it affect multimeric proteins?

Dominant-negative mutations lead to the production of a non-functional protein that interferes with the normal function of multimeric proteins, leading to a loss of function in the entire protein complex. Signup and view all the answers

Discuss the causes of haploinsufficiency and provide an example of a condition associated with this phenomenon.

Haploinsufficiency occurs when a single functioning allele is insufficient to maintain normal function, resulting in disease; an example is familial hypercholesterolemia, where mutations in one allele of the LDL receptor cause the condition. Signup and view all the answers

How do complete dominance and codominance differ in terms of expressed phenotypes in humans?

In complete dominance, only the dominant allele's phenotype is expressed, while in codominance, both alleles contribute to the organism's phenotype, as seen in the AB blood group. Signup and view all the answers

Explain the impact of mutations in the FGFR3 gene with respect to achondroplasia's developmental effects.

Mutations in the FGFR3 gene lead to its constitutive activation, inhibiting chondrogenesis and resulting in abnormal bone growth associated with achondroplasia. Signup and view all the answers

Define codominance and explain its relevance in the ABO blood group system.

Codominance occurs when both alleles in a heterozygote are fully expressed, as evidenced in the ABO blood group system, where individuals with genotype IA/IB express both A and B antigens. Signup and view all the answers

What are the consequences of agglutination during an incorrect blood transfusion?

Agglutination causes red blood cells to clump together, which can lead to severe complications and potentially be fatal. Signup and view all the answers

Explain the significance of the A>T transversion mutation in sickle cell anemia.

This mutation causes a single amino acid change from glutamic acid to valine in the beta globin protein, affecting hemoglobin function. Signup and view all the answers

Describe how varying levels of dominance manifest in sickle cell anemia among different observation levels.

At the organismal level, HbA is completely dominant; at the cellular level, there is incomplete dominance with sickle cells; and at the molecular level, both HbA and HbS are codominant. Signup and view all the answers

What does incomplete penetrance imply in the context of hereditary diseases?

Incomplete penetrance means that individuals may carry a genetic mutation without showing any symptoms of the disease. Signup and view all the answers

How does variable expressivity affect the phenotypic presentation in genetic disorders?

Variable expressivity leads to different manifestations of a genetic condition among individuals, even within the same family. Signup and view all the answers

What type of inheritance is suggested by a family tree with affected individuals but apparently normal parents?

This pattern suggests recessive inheritance, potentially involving carriers among the parents. Signup and view all the answers

What role does consanguinity play in the appearance of recessive genotypes in offspring?

Consanguinity increases the chances of both parents carrying the same recessive allele, raising the likelihood of affected offspring. Signup and view all the answers

How does the inheritance of X-linked traits lead to different phenotypic ratios in males and females?

Males have only one X chromosome, so any allele on the X will be expressed, while females can be carriers with a second X chromosome that may mask the allele. Signup and view all the answers

Describe the relationship between hemophilia and royal lineage, particularly regarding Queen Victoria.

Queen Victoria was a carrier of hemophilia, which was passed down through royal intermarriages, leading to its spread among prominent royal families. Signup and view all the answers

What is the role of the SRY gene in the development of sexual characteristics?

The SRY gene is essential for male gonadal development and male secondary sexual characteristics by promoting the formation of testes. Signup and view all the answers

How does testicular feminization syndrome exemplify the importance of androgen sensitivity?

Individuals have XY chromosomes but lack the ability to respond to androgens, leading to the development of female secondary sexual characteristics despite a male genotype. Signup and view all the answers

Explain the difference between monochromacy and dichromacy in color vision.

Monochromacy is total color blindness due to cone absence or defect, while dichromacy is a milder form where one of the three color mechanisms is missing. Signup and view all the answers

What significant finding regarding color blindness was discovered from the eyes of J. Dalton?

Scientists found a deletion of the gene coding for green opsin in Dalton's eyes, confirming a genetic basis for his color blindness. Signup and view all the answers

Discuss the impact of Barr bodies on understanding X-linked conditions in females.

Barr bodies are inactivated X chromosomes in females, indicating the presence of two X chromosomes and contributing to dosage compensation of X-linked genes. Signup and view all the answers

Why does the phenotypic expression of red and white eyes vary in an F2 generation?

This variation is due to the segregation of alleles and independent assortment, allowing for different combinations of traits to appear. Signup and view all the answers

What determines whether a female carrier of an X-linked disorder will pass the affected allele to her progeny?

A female carrier has a 50% chance of passing the affected allele to any child, regardless of the child's sex. Signup and view all the answers

Describe the implications of a haplosufficient gene concerning melanin production in individuals with genotype A/a.

Individuals with genotype A/a will produce sufficient functional tyrosinases for normal melanin production, ensuring a normal phenotype despite having one mutated allele. Signup and view all the answers

What are the consequences of the absence of functional phenylalanine hydroxylase in individuals with phenylketonuria?

The absence of functional phenylalanine hydroxylase leads to the accumulation of phenyl pyruvic acid, which interferes with nervous system development and can cause mental retardation. Signup and view all the answers

Explain how the CFTR gene mutation translates into symptoms experienced by patients with cystic fibrosis.

Mutations in the CFTR gene disrupt chloride ion transport, resulting in thick mucus buildup in the lungs and pancreas, leading to respiratory issues and digestive problems. Signup and view all the answers

What does the term 'phenocopies' imply in the context of phenylketonuria?

Phenocopies refer to different genetic causes that produce the same phenotype, such as PKU cases with mutations in either the phenylalanine hydroxylase gene or the THB co-factor gene. Signup and view all the answers

What is the selective advantage associated with heterozygote carriers of the CFTR mutation in populations historically affected by typhoid fever?

Heterozygote carriers of the CFTR mutation demonstrated reduced intestinal permeability to Salmonella typhi, providing a survival advantage during typhoid fever outbreaks. Signup and view all the answers

How does the accumulation of intermediates in PKU affect mental development?

The accumulation of intermediates like phenyl pyruvic acid can cross the blood-brain barrier, disrupting normal nervous system development and resulting in mental retardation. Signup and view all the answers

What genetic testing measures are taken for newborns at risk for phenylketonuria?

Newborns are subjected to genetic tests to identify mutations in the phenylalanine hydroxylase gene or the THB gene, allowing for early dietary interventions. Signup and view all the answers

What are the primary roles of sodium ions in the process affected by CFTR mutations?

Sodium ions passively follow chloride ions out of epithelial cells, which alters the electrolyte concentration in mucus and facilitates water movement via osmosis. Signup and view all the answers

In the inheritance of X-linked recessive disorders, why are males more frequently affected than females?

Males have only one X chromosome, so a single mutated allele will result in the disease, whereas females have two X chromosomes, allowing for one normal copy to mask the effect. Signup and view all the answers

Study Notes

Dominantly Inherited Diseases

Mutations can lead to excess function, abnormal expression, or incorrect timing of protein synthesis in tissues.
Example: Achondroplasia is caused by a mutation in FGFR3 leading to overactivation and inhibition of chondrogenesis.
Haploinsufficiency occurs when a single mutated allele causes disease, as seen in familial hypercholesterolemia involving mutations in the LDL receptor.

Dominant-Negative Mutations

Single allele mutations produce dysfunctional proteins that inhibit normal protein function, especially in multimeric proteins.
Example: Osteogenesis imperfecta arises from mutations in type I collagen, resulting in bone fragility.

Types of Dominance

Complete Dominance: Dominant homozygotes and heterozygotes show identical phenotypes.
Codominance: Found in ABO blood groups where both A and B antigens are expressed equally in AB blood type.

Blood Group Inheritance

Blood groups determined by three alleles: i, IA, and IB.
Genotypes IA/IA and IA/I yield blood group A; IB/IB and IB/I yield blood group B.
Blood group AB (IA/IB) showcases codominance, expressing both A and B antigens; O (i/i) has neither.
Incorrect transfusions can lead to agglutination, a potentially fatal reaction.

Sickle Cell Anemia

Autosomal recessive monogenic disease caused by a mutation in the beta globin allele.
Heterozygotes (HbA/HbS) are healthy carriers but may exhibit sickle-shaped red blood cells under low oxygen conditions.
Mutation A>T in codon 6 causes glutamic acid to be replaced by valine, altering hemoglobin properties.
Genotypic manifestations vary: HbA/HbA is normal; HbS/HbS exhibits severe anemia; HbA/HbS is a carrier with occasional sickle-shaped cells.

Incomplete Penetrance and Variable Expressivity

Non-penetrance: Individuals may have the mutation but not show symptoms.
Variable expressivity: Different phenotypes may manifest in individuals with the same genotype, exemplified by neurofibromatosis.

Recessive Diseases

Autosomal recessive conditions often present in offspring of healthy parents.
Albinism results from tyrosinase mutations causing a lack of melanin production; genotypes A/A and A/a produce normal skin color, while a/a leads to albinism.

Phenylketonuria (PKU)

Autosomal recessive disorder due to phenylalanine hydroxylase deficiency, affecting tyrosine synthesis.
Accumulation of phenyl pyruvic acid can result in neurological damage.
Not all PKU patients have mutations in the enzyme; some have mutations in the co-factor gene THB (tetrahydrobiopterin).

Cystic Fibrosis

Most common autosomal recessive disorder in Europe caused by CFTR gene mutations affecting chloride channels.
Common mutation: delF508, a deletion of phenylalanine.
Characterized by thick mucus accumulation in lungs and digestive issues, leading to respiratory failure.

Sex-Linked Inheritance

X-linked recessive conditions primarily affect males; females are typically carriers.
Example: Hemophilia, a disorder affecting blood clotting due to mutations in coagulation factors.
Color blindness, particularly red-green color vision deficiency, is another common X-linked condition.

Color Vision Defects

Monochromacy leads to total color blindness; dichromacy allows limited color perception.
Dichromacy can be classified based on affected photoreceptors (red, green, blue).
Color blindness is hereditary and predominantly affects males due to its X-linked nature.

Evolutionary Considerations

Different sex chromosomes (XX in females, XY in males) have been maintained throughout evolution to facilitate embryonic development processes.### Y and X Chromosomes in Evolution
Y chromosome has decreased in size over evolution, resulting in fewer genes, with SRY as the most critical gene.
X chromosome adopted a different evolutionary strategy, maintaining more genes.

Barr Body and X Inactivation

Barr body: inactivated X chromosome in female cells, indicated by an opaque dot in nuclei images.
Multiple Barr bodies (e.g., XXXX genotype) indicate multiple X chromosomes with random inactivation occurring early in embryonic development (10-20 cell stage).
Females exhibit mosaicism regarding the active X chromosome, leading to variable expression of mutations depending on the tissue.

Genetic Conditions and Female Carriers

Expression of X-linked mutations in females can lead to a mix of normal and mutated alleles across tissues.
In conditions like hemophilia, female carriers may show biochemical abnormalities without clinical symptoms.
Ectodermal dysplasia exemplifies a phenotype with restricted expression to certain cells, creating a patchwork appearance.
Non-random X inactivation can lead to unexpected patterns of gene expression, where critical tissue inactivates the normal allele causing severe symptoms.

Bruton’s Agammaglobulinemia

Characterized by absence of mature B lymphocytes due to mutation in gene crucial for their maturation.
Affects males significantly, while heterozygous females have mature B lymphocytes but may still express the mutated allele through X inactivation.

Duchenne Muscular Dystrophy

Caused by mutations in the dystrophin gene, located in muscle tissues including heart muscles.
Symptoms include progressive muscle weakness, early onset (2-4 years), limited life expectancy (15-25 years), and potential cardiac issues.
Dystrophin is essential for muscle fiber integrity and signaling with extracellular matrix, mutations lead to muscle fiber death.

Genetics of Deafness

Genetic causes of deafness are heterogeneous, affecting approximately 1 in 100 children, with 1 in 300 experiencing significant impairment.
Potential genetic syndromes include autosomal dominant, autosomal recessive, X-linked, and, rarely, mitochondrial inheritance.
Most cases arise from autosomal recessive mutations; complementation can occur when mutations affect different genes from both parents, leading to normal development.
Intragenic complementation (mutations in the same gene) is rare; intergenic complementation (mutations in different genes) is more frequently observed.