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Genetics > Asthma 03/11/22 > Flashcards

Asthma 03/11/22 Flashcards

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Biology 101 flashcards
1
Q

Why are chromosomes packed?

A

-Naked DNA molecules are unstable within cells & packaging DNA protects the molecule from damage
-Compaction allows long DNA molecule to fit within a cell
-Allows efficiency of DNA replication & transfer to daughter cells
-Organisation of genome allows for regulation of gene expression

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2
Q

What is a allele?

A

Allele is a nucleotide sequence of a gene. Alleles are variants of the same gene that occur on the same place on a chromosome. Through a mutation, they are different. Responsible for variable traits within a population.

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3
Q

What is a locus?

A

A locus refers to the position of an allele on the chromosome. Serves as a marker. Different loci consist of different alleles.

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4
Q

What is a gene?

A

The basic unit of inheritance, by which hereditary characteristics are transmitted from parents to offspring. At the molecular level a single gene consists of DNA which exerts its influence on the organism’s form & function by encoding & directing the synthesis of a protein, tRNA, rRNA or other structural RNA.

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5
Q

What is a genome?

A

The complete DNA sequence of an organism, consisting of gene encoding DNA sequences & non-encoding DNA sequences.

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6
Q

What is genomics?

A

Discipline of sequencing, mapping, analysing, and comparing genomes.

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7
Q

What is the study of genetics?

A

-Genetics is the study of heredity.
-Gene refers to a specific sequence of DNA on a single chromosome.
-Genetics involves the study of functions and composition of the single gene.

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8
Q

What is the study of genomics?

A

-Genomics is the study of the entirety of an organism’s genes.
-Genome refers to an organism’s entire genetic makeup.
-Genomics addresses all genes and their inter relationships.

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9
Q

What is a single nucleotide polymorphism?

A

The most common type of genetic variation among people.
Each SNP represents a difference in a single DNA building block (nucleotide). They can act as biological markers, helping scientists locate genes that are associated with disease.

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10
Q

What is epigenetics?

A

Refers to changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence. Environmental challenges can affect gene expression through epigenetic mechanisms. It is described as a heritable regulation of gene transcription that does not require alterations in gene sequence.

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11
Q

What are epigenetic regulatory factors?

A

Epigenetic regulation affects gene expression through three main mechanisms:
-DNA methylation
-Histone modifications
-Non-coding RNA

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12
Q

What is DNA methylation?

A

It is the addition of a methyl (CH3) group to DNA:
-C5-methylcytosine (5-mc)
-Occurs at Cytosine that are followed immediately by a -Guanine (CpG Dinucleotide) in gene promotor, by DNA methyltransferase (DNMT)

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13
Q

What does DNA methylation do?

A

Can cause long-term inactivation of genes in cellular differentiation and regulates expression of either the maternal or paternal alleles of certain genes at the start of development.

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14
Q

How does DNA methylation work?

A

It is a covalent modification of DNA that does not change the DNA sequence but has an influence on gene activity. Although is heritable, it is reversible, this can act as a therapeutic target. Changes to DNA methylation leads to gene activation.

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15
Q

What is a histone?

A

Histones are a group of proteins found in the nuclei of eukaryotic cells responsible for DNA folding and chromatin formation. Chromatin architecture, nucleosomal positioning, and ultimately access to DNA for gene transcription, is largely controlled by histone.

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16
Q

What does a histone do?

A

Each nucleosome is made of two identical subunits, each of which contains four histones - H2A, H2B, H3, and H4.
The H1 protein acts as the linker histone to stabilise internucleosomal DNA and does not form part of the nucleosome itself.

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17
Q

What does histone modification do and include?

A

A histone modification is a covalent post-translational modification (PTM) to histone proteins.

This includes:
-Acetylation
-Methylation
-Phosphorylation
-Ubiquitylation
-Sumoylation (Small Ubiquitin-like Modifier (or SUMO) proteins are a family of small proteins that are covalently attached to and detached from other proteins)

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18
Q

What is histone acetylation?

A

Histones are catalysed by Histone acetyl transferase (HATs) enzymes. This adds an acetyl group to histone tails (especially H3 and H4). This reduces positive charge and weakens interaction of histones with DNA ad facilitates transcription by making DNA more accessible to RNA polymerase II.

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19
Q

What is histone deacetylation?

A

Histones are catalysed by Histone deacetylases (HDACs) enzymes. This removes acetyl groups from histone tails and increases interaction between DNA and histones and represses transcriptions.

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20
Q

What processes are histone acetylation involved in?

A

The process of histone acetylation is tightly involved in the regulation of many cellular processes including:
-chromatin dynamics and transcription
-gene silencing
-cell cycle progression
-apoptosis
-differentiation
-DNA replication
-DNA repair
-nuclear import
-neuronal repression

21
Q

What effect can an imbalance of acetylation and deacetylation cause?

A

An imbalance in the equilibrium of histone acetylation has been associated with tumorigenesis and cancer progression.

22
Q

What groups can histone acetylation be classified into?

A

More than 20 HATs have been identified which can be classified into five families:

-GNAT1
-MYST
-TAFII250
-P300/CBP
-nuclear receptor coactivators such as ACTR

23
Q

How is histone H3 acetylation increased?

A

Histone H3 acetylation may be increased by inhibition of histone deacetylases (HDACs) and decreased by HAT inhibition

24
Q

What groups can histone deacetylation be classified into?

A

At least 4 classes of HDACs have been identified:
-Class I HDACs include 1, 2, 3, and 8
-Class II HDACs are comprised of 4, 5, 6, 7, 9, and 10
-Class III enzymes, known as sirtuins, require NAD+ cofactors and include SIRTs 1-7
-The Class IV enzyme, which contains only HDAC11, has features of both Class I and II

25
Q

What processes are histone deacetylation involved in?

A

HDAC inhibition displays significant effects on apoptosis, cell cycle arrest, and differentiation in cancer cells. HDAC inhibitors are currently being developed as anticancer agents.

26
Q

What is non-coding RNA and the different types?

A

It is a functional RNA molecule that is not translated into protein.

Types:
-microRNA
-Silencing RNA
-Small nuclear / nucleolar RNA
-Circular RNA

27
Q

What is a microRNA (miRNA)?

A

It is a small non-coding RNA molecule (containing about 22 nucleotides). It is found in plants, animals and some viruses.

Functions:
-RNA silencing
-post-transcriptional regulation of gene expression

28
Q

What is the processing and function of miRNA?

A

miRNA is transcribed as long hairpin primary RNA (pri-miRNA) by RNA polymerase II.

Drosha ribonuclease III and the RNA-binding DGCR8 protein make it become pre-miRNA.

This pre-miRNA then is exported to the cytoplasm by exportin-5 protein.

Dicer then makes it become a mature miRNA and this binds with RISC complex to cause gene silencing.

29
Q

What are the functional consequences of changed miRNA expression?

A

Diagnosis, prognosis, and severity of a wide range of diseases including:

-infectious disease
-autoimmune diseases
-cancer

30
Q

What are the functions of the respiratory system?

A

-Provides an extensive area for gas exchange between the air and the circulatory blood
-Maintenance of homeostasis (e.g., regulation of blood pH)
-Exchanges gases between the bloodstream and body tissues
-Olfactory sensation (sense of smell)
-Voice production
-Defence against pathogens

31
Q

What structures are in the upper respiratory tract?

A

-Nose
-Nasal cavity
-Pharynx

32
Q

What structures are in the lower respiratory tract?

A

-Larynx
-Trachea
-Bronchi
-Lung

33
Q

What is the larynx made up of?

A

Glottis - the superior opening; the part of the larynx consisting of the vocal cords and the opening between them. It affects voice modulation through expansion or contraction.
Epiglottis - the flap of tissue that guard’s the glottis, directs food and drink to oesophagus.

34
Q

What is the function of the larynx?

A

-Maintain an open passageway for air movement
-Epiglottis and vestibular folds prevent swallowed material from moving into larynx
-Vocal cords are primary source of sound production

35
Q

What is the trachea?

A

Rigid tube, 12 cm long and 2.5 cm in diameter, anterior to oesophagus. Supported by 16 to 20 C-shaped cartilaginous rings (hyaline cartilage). Trachealis muscle (smooth muscle) spans opening in rings, adjusts airflow by expanding or contracting. Larynx and trachea lined with ciliated pseudostratified epithelium which functions as mucociliary escalator.

36
Q

What is the structure of the tracheobronchial tree?

A

Trachea -> Pri bronchi -> Sec bronchi -> tertiary bronchi -> bronchioles -> terminal bronchioles

37
Q

What are the bronchioles?

A

Bronchioles (lack cartilage) - 1mm. They have a layer of smooth muscle and pulmonary lobule ventilated by one bronchiole. It divides into 50 - 80 terminal bronchioles.

38
Q

What are terminal bronchioles?

A

Terminal bronchioles - 0.5mm. They have cilia, divide into 2 or more respiratory bronchioles.

39
Q

What are respiratory bronchioles?

A

Respiratory bronchioles divide into 2-10 alveolar ducts.
Alveolar ducts - end in alveolar sacs and the alveolar sacs contains alveoli.

40
Q

What is the ciliated mucosa?

A

It is one of the major defence mechanisms which protect the lung. It covers most of the bronchi, bronchioles, and nose.
It contains mucus-producing goblet cells and ciliated epithelium. Continuously propels the mucus which contains dust particles and debris to the throat so it can be expelled or swallowed.

41
Q

What is the site of gas exchange?

A

The Alveoli increases the surface area and brings air in contact with blood. Around 300 million air sacs and this is where gas exchange takes place. Large surface area (60 – 80 m2) makes up 40 times total body surface (size of a football pitch). They are 0.2 –0.5 mm in diameter. Alveolar membranes are thin, and each alveolus is 1 cell layer thick.
Total air barrier is 2 cells across (0.5 µm).

42
Q

What is the alveoli?

A

Cell types of the Alveoli:

Alveolar type I - (95%)
Structural cells - simple squamous cells where gas exchange occurs

Alveolar type II: (5%)
Free surface has microvilli and secrete surfactant (phospholipid+ lipoprotein). Alveolar macrophages (dust cells) to remove debris.

43
Q

Asthma statstics?

A

it is a common chronic disease. It affects about 5 million people in the UK and costs the UK health service at least £1.1 billion each year.

44
Q

How is asthma characterised?

A

It is characterised by:

-variable and recurring respiratory symptoms
-wheezing
-coughing
-chest tightness
-shortness of breath
-reversible airflow obstruction associated with airway hyperresponsiveness (AHR)
-bronchospasm

45
Q

What causes the characteristics of asthma?

A

These features are generally attributed to an airway inflammatory process with progressive bronchial remodelling.

46
Q

What are the triggers of asthma?

A

Allergens:

-house dust mites
-animal fur or pollen
-smoke, pollution and cold air
-stress
-exercise
-infections like colds or flu

47
Q

What happens in structural remodelling?

A

The airways in asthma undergo significant structural remodelling. Medium-sized airways from a normal and severe asthmatic patient were sectioned and stained using Movat’s pentachrome stain. The epithelium in asthma shows mucous hyperplasia and hyper secretion (blue), and significant basement membrane thickening. Smooth muscle volume is also increased in asthma.

48
Q

How do epigenetics play a role in asthma?

A

DNA methylation. White circles represent unmethylated CpGs that induces gene expression (e.g., KRT5) while black circles represent methylated CpGs that suppresses gene expression (e.g., STAT5A). B)

Histone acetylation. Green circles refer to acetylated histone tail that stimulate gene expression (e.g., ΔNp63) while red circles indicate free histone tails that suppressed gene expression.

Noncoding RNA. miRNAs affect gene expression by either RNA degradation or translational inhibition. miRNAs hence (e.g., miR-19a) may suppress mRNA expression (e.g., TGF-β receptor 2).

Genetics (17 decks)

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