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Question 1

Why do the immune cells of older men lose their Y chromosomes?

Answer 1

• Y chromosome is small and contains few essential genes
• DNA replication becomes less accurate with age
• Loss during stem cell division leads to clonal expansion of Y-less cells
• Immune cells derived from these stem cells accumulate over time

The loss of Y chromosomes in immune cells can have significant implications for health.

Question 2

How does Y chromosome loss increase the risk of heart disease, cancer, and Alzheimer’s disease?

Answer 2

• Disrupts normal immune function
• Leads to chronic inflammation and reduced surveillance for abnormal cells
• Y-lacking immune cells release TGF-β, causing fibrosis in the heart
• Impaired detection allows mutated cells to proliferate in cancer
• Contributes to neurodegeneration in Alzheimer’s
• Creates systemic immune dysregulation

Chronic inflammation can be a precursor to various diseases.

Question 3

How can DNA replication errors lead to diseases like heart disease, cancer, or Alzheimer’s?

Answer 3

• Replication errors cause mutations or chromosome loss
• Mutations in oncogenes or tumor suppressor genes lead to cancer
• Y chromosome loss disrupts immune response leading to chronic inflammation
• In heart: fibrosis from immune cell dysfunction causes heart failure
• In brain: faulty immune clearance leads to protein buildup
• Accumulated damage impairs organ function and increases disease risk

The relationship between DNA replication errors and diseases is crucial for understanding cancer biology.

Question 4

Why do men lose the Y chromosome in their bone marrow?

Answer 4

• High proliferation in bone marrow due to frequent division of hematopoietic stem cells
• Frequent cell division increases chances of DNA replication errors
• Y chromosome’s small size makes it susceptible to loss during replication errors

This loss can have significant implications for immune function.

Question 5

Why is Y chromosome loss less common in other tissues?

Answer 5

• Lower cell turnover in many tissues results in fewer replication errors
• Reduced cumulative risk due to fewer cell cycles

This highlights the importance of cell division rates in genetic stability.

Question 6

How does Y chromosome loss in bone marrow raise cancer risk?

Answer 6

• Reduces immune surveillance for abnormal cells
• Allows mutated cells to escape detection
• Leads to unchecked proliferation and tumor formation
• Associated with reduced lifespan

The immune system plays a critical role in cancer prevention.

Question 7

Why are DNA errors linked to cancer?

Answer 7

• Mutations disrupt genes controlling cell division and repair
• Affect tumor suppressor genes or oncogenes leading to uncontrolled growth
• Errors can cause genomic instability increasing further mutations
• Loss of apoptosis allows damaged cells to survive and multiply

Understanding these mechanisms is essential for cancer research.

Question 8

List reasons for why the Y Chromosome is shrinking.

Answer 8

• Lack of recombination
• Gene loss due to mutations
• Evolutionary inversions
• Selection for essential genes
• Stabilization over time

The evolutionary history of the Y chromosome is a subject of significant interest in genetics.

Question 9

How can ‘a brew of growth factors and other proteins’ stimulate induced pluripotent stem cells?

Answer 9

• Growth factors bind to receptors on pluripotent stem cells
• Activates transcription factors
• Causes the stem cell to proliferate/divide
• Differentiates to carry out a particular function

This process is crucial for regenerative medicine and tissue engineering.

Question 10

Why can stem cells survive if they lose their Y chromosome?

Answer 10

• Y chromosome contains relatively few essential genes
• Loss does not prevent basic survival functions
• Cells can still divide and produce immune cells
• Other chromosomes provide necessary cellular functions

This demonstrates the redundancy of genetic information in cells.

Question 11

Why would stem cells die if they lost any other chromosome?

Answer 11

• Other chromosomes carry many essential genes for metabolism and DNA repair
• Loss of such genes is usually lethal
• Leads to cell cycle arrest or apoptosis
• Cells lacking critical chromosomes are not viable

The importance of chromosomal integrity is critical for cell survival.

Question 12

How does stem cell survival without the Y chromosome lead to many immune cells lacking Y?

Answer 12

• A stem cell that loses the Y chromosome can still divide
• Gives rise to a clonal population of Y-lacking immune cells
• Over time, these cells make up a growing percentage of total immune cells
• Explains mosaicism in immune cell chromosomes in older men

This phenomenon has implications for understanding aging and immune function.

Question 13

How does faulty DNA replication lead to Y chromosome loss?

Answer 13

• Errors during mitosis can cause improper chromosome segregation
• Y chromosome, being small, is more likely to be mis-segregated or lost
• Replication stress or spindle defects increase error frequency
• Leads to daughter cells without a Y chromosome

Understanding these mechanisms can aid in developing therapies for age-related diseases.

Question 14

How was CRISPR gene editing used to remove the Y chromosome in this study?

Answer 14

• CRISPR targeted and cut DNA sequences specific to the Y chromosome
• Editing was done in hematopoietic stem cells
• Resulted in ~⅔ of immune cells lacking the Y chromosome
• Mimicked age-related Y chromosome loss seen in men

CRISPR technology is revolutionizing genetic research.

Question 15

What are the benefits of using CRISPR to remove the Y chromosome in this experiment?

Answer 15

• Allows precise gene targeting and control over chromosome loss
• Can test causal links between Y loss and disease
• Creates consistent experimental conditions in animal models
• Helps model a human-specific phenomenon in mice

This precision is crucial for understanding genetic diseases.

Question 16

What are the advantages and disadvantages of using mice in this experiment?

Answer 16

Advantages:
• Share key genetic and physiological traits with humans
• Short lifespan enables study of age-related disease quickly
• Genetically modifiable and ethically accepted
Disadvantages:
• Mouse immune and cardiovascular systems differ
• Results may not fully translate to human physiology
• Ethical concerns exist regarding genetic modification

The use of animal models is a topic of ongoing ethical debate.

Question 17

Why did mice develop heart disease at around 1 year of age in this study?

Answer 17

• 1-year-old mice are equivalent to elderly humans
• Heart disease developed due to progressive immune dysfunction
• Accumulated effects of Y-lacking immune cells caused damage
• Mirrors slow onset of age-related disease in humans

This correlation aids in understanding human aging.

Question 18

Why do researchers use animal models when investigating human diseases?

Answer 18

• Minimizes overall cost
• Much knowledge of diseases and treatments comes from using animals
• Animals share a large number of genes with humans
• Easier to keep isolated in cages
• Cheaper to maintain

Animal models are invaluable in biomedical research.

Question 19

Name one non-animal alternative that can be used in research and give an advantage of this alternative method.

Answer 19

• Tissue Culture / Computer modelling
• More ethical, no animals harmed
• Easy to culture
• Cheaper continual supply

Non-animal alternatives are important for ethical research practices.

Question 20

Why did the heart muscle of the mice become scarred?

Answer 20

• Y-lacking immune cells infiltrated the heart tissue
• These cells released TGF-β, a pro-fibrotic signaling molecule
• TGF-β triggered fibroblast activation, leading to collagen deposition
• Resulted in fibrosis (scarring) of heart muscle

Fibrosis can severely impact heart function.

Question 21

How can scarring of the heart muscle contribute to heart failure?

Answer 21

• Scar tissue is non-contractile and reduces cardiac output
• Fibrosis disrupts normal electrical conduction in the heart
• Leads to stiffening and reduced elasticity of heart muscle
• Impairs the heart’s ability to pump efficiently, causing failure

Understanding heart failure mechanisms is crucial for developing treatments.

Question 22

How is the release of transforming growth factor beta (TGF-β) triggered?

Answer 22

• Y-lacking immune cells infiltrate cardiac tissue
• Triggers an inflammatory response
• Cells release TGF-β as a signaling molecule
• Initiates a cascade promoting tissue fibrosis

TGF-β plays a significant role in inflammation and fibrosis.

Question 23

What is the effect of TGF-β as an inflammatory signalling molecule?

Answer 23

• Stimulates fibroblast activation
• Increases collagen production leading to fibrosis
• Promotes tissue remodeling and scar formation
• Contributes to organ dysfunction, e.g., in the heart

TGF-β is a key player in wound healing and fibrosis.

Question 24

How does an antibody block this growth factor?

Answer 24

• Antibody binds specifically to TGF-β, neutralizing it
• Prevents TGF-β from binding to its cell surface receptor
• Inhibits signal transduction pathways responsible for fibrosis
• Reduces scarring and inflammation

Antibody therapies are an emerging treatment strategy.

Question 25

Describe the inflammatory immune response.

Answer 25

• Triggered by tissue damage or infection • Mast cells release histamine, causing vasodilation • Increases blood flow and attracts phagocytes • Leads to swelling, redness, and heat ## Footnote The inflammatory response is crucial for pathogen elimination.

Question 26

Explain antibody action and phagocytosis.

Answer 26

• Antibodies bind antigens, causing agglutination • Mark pathogens for destruction • Phagocytes engulf and digest them • Part of the specific immune response ## Footnote This process is vital for the adaptive immune system.

Question 27

How can a blood test detect loss of Y chromosomes in immune cells?

Answer 27

• Blood is sampled and immune cells are isolated • Techniques like PCR quantify Y-specific sequences • Compare Y chromosome content across cells • Indicates % of immune cells that have lost the Y chromosome ## Footnote PCR is a powerful tool for genetic analysis.

Question 28

How do chromosomal combinations like XXY or XYY occur?

Answer 28

• Caused by nondisjunction during meiosis • Leads to abnormal gametes with extra sex chromosomes • XXY (Klinefelter’s): infertility, low testosterone, learning difficulties • XYY: taller stature, may have speech/learning issues • Genetic disorders caused by imbalance in gene dosage ## Footnote Understanding chromosomal abnormalities is important in genetics.

Question 29

What could be the effect of Y chromosome loss in individuals with XYY?

Answer 29

• One Y chromosome lost → individual becomes typical XY • If Y loss occurs in many cells → mosaicism • May affect fertility or cell function depending on affected cells • Possibly less severe than total Y loss in XY males ## Footnote Mosaicism can have varying clinical implications.

Question 30

How has the Y chromosome lost hundreds of genes over time?

Answer 30

• Y stopped recombining with X due to inversions • Accumulated deleterious mutations without repair • Natural selection could not eliminate these mutations • Resulted in genetic decay and loss of non-essential genes ## Footnote The evolutionary trajectory of the Y chromosome is a significant area of study.

Question 31

How does each chromosome copy act as a genetic backup?

Answer 31

• Diploid organisms have homologous chromosome pairs • Each gene exists in two copies (alleles) • One allele can often compensate if the other is mutated • Provides genetic redundancy and increases survival ## Footnote Genetic redundancy is crucial for maintaining stability in populations.

Question 32

Describe the structure of a nucleotide pair.

Answer 32

• Contains deoxyribose sugar, phosphate, and bases • Mononucleotides/bases held together by hydrogen bonds • Between complementary bases ## Footnote This structure is fundamental to understanding DNA and its replication.

Question 33

Describe the process of DNA replication.

Answer 33

• DNA unzipped by helicase breaking hydrogen bonds between bases • DNA mononucleotides line up along the template strand by complementary base pairing • Complementary nucleotides added by DNA polymerase forming phosphodiester bonds • Semi-conservative: each new molecule has 1 old, 1 new strand • Ensures genetic continuity ## Footnote DNA replication is a vital process for cell division.

Question 34

What are mutations and their types?

Answer 34

• Changes in DNA sequence • Types: substitution, deletion, insertion • Effects: silent, missense, nonsense, frameshift • Can be beneficial, harmful, or neutral ## Footnote Mutations are fundamental to evolution and genetics.

Question 35

Explain what is meant by the phrase 'gene variants'.

Answer 35

• Alternative versions/alleles of a gene • Due to changes in the base sequence of the DNA ## Footnote Gene variants contribute to phenotypic diversity.

Question 36

What is the difference between gene mutations and chromosomal mutations?

Answer 36

• Gene mutation is a change in the nucleotide sequence of a particular gene • Chromosomal mutation is a change in several genes in the chromosome • Gene mutation is a slight structural alteration • Chromosomal mutations are either numerical or structural changes in the entire DNA strand ## Footnote Understanding these differences is crucial for genetic analysis.

Question 37

Explain crossing over and its significance in reproduction.

Answer 37

• Occurs in prophase I of meiosis • Homologous chromosomes exchange allele/genetic material at chiasmata • Produces new allele combinations • Increases genetic variation among offspring • Important for evolution and adaptability • Errors in crossing over can lead to mutations ## Footnote Crossing over is a key mechanism for generating genetic diversity.

Question 38

How does meiosis lead to genetic variation?

Answer 38

• Crossing over during prophase I creates recombination • Independent assortment of chromosomes in metaphase I • Results in gametes with different combinations of alleles • Fertilization further increases variation • Ensures no two offspring are genetically identical (except identical twins) • Drives natural selection and evolution ## Footnote Meiosis is essential for sexual reproduction and diversity.

Question 39

Describe how genes can be switched off by transcription factors.

Answer 39

• Transcription factors are proteins • Bind to sections of DNA • Regulate gene expression by promoting or inhibiting transcription ## Footnote Transcription factors play a crucial role in gene regulation.

Question 40

What creates genetic variation during prophase I?

Answer 40

Crossing over creates recombination ## Footnote This process allows for the exchange of genetic material between homologous chromosomes.

Question 41

What contributes to genetic variation during metaphase I?

Answer 41

Independent assortment of chromosomes ## Footnote This process ensures that chromosomes are distributed randomly into gametes.

Question 42

What is the result of fertilization in terms of genetic variation?

Answer 42

It increases variation by combining alleles from two parents ## Footnote This leads to unique genetic combinations in offspring.

Question 43

Why are no two offspring genetically identical (except identical twins)?

Answer 43

Due to the processes of recombination and independent assortment ## Footnote These processes create unique genetic combinations in each gamete.

Question 44

How does natural selection relate to genetic variation?

Answer 44

It drives evolution by favoring individuals with advantageous traits ## Footnote Variability in traits allows for survival and reproduction advantages.

Question 45

What role do transcription factors play in gene expression?

Answer 45

They are proteins that bind to DNA and regulate transcription ## Footnote This can involve processes such as methylation or deacetylation.

Question 46

How can gene mutations affect the Y chromosome?

Answer 46

Different lengths of Y chromosomes may provide selective advantages in specific environments ## Footnote This can lead to evolutionary changes over time.

Question 47

What environmental factor can influence sex determination in some species?

Answer 47

Incubation temperature ## Footnote This affects hormone levels during development in reptiles and fish.

Question 48

What is the interaction between environment and phenotype?

Answer 48

Environment influences gene expression and traits ## Footnote Examples include diet, temperature, and light exposure.

Question 49

What gene mutation is associated with male development?

Answer 49

Mutation of a gene to become the SRY gene ## Footnote This triggers the development of male characteristics.

Question 50

What problems arise from gene inversion on the Y chromosome?

Answer 50

Inversions prevent alignment with the X chromosome during meiosis ## Footnote This can lead to mutations and gene loss.

Question 51

What is a disadvantage of having only one Y chromosome?

Answer 51

No backup copy for Y-linked genes ## Footnote This increases the risk of genetic diseases.

Question 52

List advantages of having multiple copies of genes on the Y chromosome.

Answer 52

* Provides backup in case of mutation * Increases gene expression efficiency * Enhances spermatogenesis and fertility * Maintains gene function despite no recombination ## Footnote These advantages help ensure reproductive success.

Question 53

How do regulatory genes control gene expression?

Answer 53

They encode transcription factors that activate or repress transcription ## Footnote This regulation affects development, cell cycle, and metabolism.

Question 54

What occurs when one X chromosome is inactivated in females?

Answer 54

Forms Barr bodies to prevent overexpression of X-linked genes ## Footnote This ensures gene dosage parity with males.

Question 55

What are the phases of clinical trials?

Answer 55

* Phase 1: Tests safety, dosage, side effects in healthy volunteers * Phase 2: Tests efficacy and monitors adverse reactions in patients * Phase 3: Compares with existing treatments in large patient groups ## Footnote Double-blind methods are often employed to reduce bias.

Question 56

Define 'randomised' in clinical trials.

Answer 56

Patients are assigned to treatment or placebo groups randomly ## Footnote This helps eliminate selection bias.

Question 57

What does 'double-blind' mean in clinical trials?

Answer 57

Neither the patient nor the doctor knows the treatment assignment ## Footnote This removes bias in result recording.

Question 58

What is the purpose of a placebo-controlled trial?

Answer 58

To assess improvements without an active drug's influence ## Footnote This can help identify the placebo effect.

Question 59

What imaging technique uses magnetic fields for structural imaging?

Answer 59

MRI ## Footnote It is commonly used for diagnosing brain disorders.

Question 60

What does fMRI measure?

Answer 60

Maps brain activity by detecting oxygenated blood ## Footnote This helps in understanding brain function.

Question 61

What does PET imaging utilize?

Answer 61

Radioactive tracers to measure metabolic activity ## Footnote It is useful in diagnosing brain disorders.

Question 62

Describe the mechanism of the heart.

Answer 62

* SA node initiates impulse * Signal relayed to AV node * Spreads via Purkinje fibres to ventricles ## Footnote This coordinates rhythmic contraction and blood flow.

Question 63

How do acetylcholinesterase inhibitors help in treating Alzheimer's disease?

Answer 63

* Prevent breakdown of acetylcholine * Increase availability to post-synaptic receptors ## Footnote This compensates for reduced acetylcholine production.