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Cystic Fibrosis - Coggle Diagram

- - - - Inheritance pattern
        
        autosomal recessive
        
        inherits 2x CFTR gene; 1 each parent
        
        each parent heterozygous?
        
        25% chance child CF
        
        1/4
        
        50% hetero inheritance (norm. + mutate)
        
        2/4
        
        25% chance normal
        
        1/4
        
        carrier frequency - 1 in 25
        
        1 in 2500 live births
      - common = Caucasian northern Europe ethnicity
      - non-infectious genetic disorder
    - - mutation defect in CFTR gene
        
        CFTR = cystic fibrosis transmembrane conductance regulator
        
        every organ makes mucus + digestive juices
        
        epithelial cells
        
        unable code protein correct
        
        effect on protein
        
        Class 1
        
        production CFTR = stop early
        
        no functional CFTR
        
        Class 2
        
        deform CFTR fold improperly
        
        trap in endoplasmic reticulum
        
        Class 3
        
        arrive @ membrane
        
        ion channel not able open properly
        
        1 more item...
        
        Class 4
        
        arrive @ membrane
        
        ion channel misshaped
        
        1 more item...
        
        Class 5
        
        success CFTR decrease
        
        low lvls fnctnl CFTR
        
        protein regulates movement of chloride in and out of cells
        
        osmosis > salt out, water in
        
        chloride = stay in cell
        
        imbalance
        
        1 more item...
        
        chloride flow helps water mvmnt in tissues
      - Mutation
        
        Where
        
        Chromo 7, long arm
        
        Position 31.2 chromo
        
        508th position protein
        
        CFTR gene
        
        2,000 mutations
        
        Point
        
        (delta) ΔF508
        
        deletion of phenylalanine
        
        66%
        
        Most common: 60-70% sufferers
        
        When
        
        Translation
        
        Effects proper synthesis of channel protein CFTR
        
        affects lining epithelium of respiratory tract
        
        leads to
        
        incorrectly made protein
        
        no protein
        
        not enough protein
    - - physical
        
        symptoms
        
        respiratory
        
        persistent cough w/ thick mucus
        
        wheezing
        
        exercise intolerance
        
        repeated lung infections
        
        inflamed nasal passages or stuffy nose
        
        recurrent sinusitis
        
        damaged airways
        
        nasal polyps
        
        digestive
        
        foul smelling, greasy poos
        
        poor weight gain and growth
        
        intestinal blockage
        
        chronic or severe constipation
        
        liver disease
        
        diabetes
        
        reproduction
        
        infertility in men
        
        reduced fertility in women
        
        other
        
        osteoperosis
        
        mental health issues
        
        depression
        
        isolation
        
        anxiety
        
        loneliness
        
        paranoia
        
        increased sweat
        
        normal kids = <50mmol/L
        
        CF kids = 70mmol/L
        
        result
        
        infections
        
        inflammation
        
        respiratory failure
        
        rectal prolapse from constipation
        
        extensive damage
        
        mucus becomes sticky + thick
        
        sufficient mvmnt and removal = difficult
        
        mucus
        
        blocks passageways, ducts
        
        increase infection
        
        staphyloccocus aureus = common
        
        traps bacteria
      - organs affected
        
        lungs
        
        liver
        
        pancreas
        
        mucoviscidosis
        
        intestines
        
        anything with mucus
        
        exocrine glands
    - - Gene therapy
      - Screening
        
        prenatal
        
        determine if genetic disease is being carried
        
        amniocentesis - beginning second trimester
        
        chorionic villus - 1st trimester
      - Accessible tech
        
        ACT - airway clearance technique
        
        coughing, huffing
        
        high frequency vest wall oscillation
        
        inflatable vest attached to machine
        
        vibrates at high frequency
        
        vibrates chest - loosen an thin mucus
        
        every 5 mins, stops > person cough and huff
      - physical therapy
        
        AD - autogenic drainage
        
        different speeds breathing to loosen mucus
        
        ACBT - active cycle of breathing technique
        
        Phase 3
        
        force mucus out of lungs
        
        Phase 2
        
        helps air behind mucus and lungs
        
        Phase 1
        
        relax airways
      - antibiotics
      - lung transplant
      - medication
        
        vitamin supplements
        
        A, D, E, K
        
        antibiotics
        
        oral, inhaled, intravenous
        
        bronchidilators
        
        open airways
    - - 8 years
        
        with tech advancements = 30-40 years
  - - - mutagens
        
        chemical
        
        naturally occurring
        
        electromagnetic radiation
      - change in nucleotide sequence
    - - abnormality in gene
        
        can effect phenotype and genotype
    - - point
        
        single nucleo variation > e.g. GTG, GAG
        
        effects
        
        silent
        
        no aa changed, DNA sequence changed
        
        missense
        
        aa change
        
        nonsense
        
        aa change to stop codon (UAG, UGA, UAA) - u=uracil
        
        neutral
        
        DNA seq = change, aa = same
        
        cause
        
        insertion
        
        base pair added
        
        deletion
        
        base pair deleted
        
        repeat expansion
        
        repeated base pair sequence
        
        substitution
        
        replacement base pair
      - chromosomal
        
        large scale
        
        structure and # changed
        
        detrimental to health
        
        causes
        
        duplication
        
        deletion
        
        inversion
        
        one pair from codon flipped
        
        translocation
        
        position changed
    - - somatic
        
        replication errors
        
        meiosis (interphase), IPMAT
        
        not all cells affected
        
        daughter cells
        
        enviro factors; lifestyle
      - germline
        
        parent inherited
        
        sex repro. cells
        
        gametes
        
        passed onto offspring
        
        ergo all cells affected
        
        meiosis
        
        growth and development
        
        mutation continuously copied
  - - - gene mutation
        
        protein produced improperly
        
        function affected
        
        monogenic = one gene
        
        multifactorial inheritance disorder = multiple genes
      - damage to chromosome
  - - - mutations
        
        ^ genetic variation
      - driven by environmental pressures
    - - genetic diversity
      - natural selection
  - - - carry instructions for building proteins
        
        genes encoded in proteins = function
    - - two copies of each gene, maternal & paternal
      - passed on through reproduction
    - - exist in different forms
        
        alleles
        
        adds to genetic variation
        
        combination of alleles
        
        received from parents
        
        determines
        
        phenotype
        
        2 more items...
        
        genotype
        
        2 more items...
- - - - see what bind to CFTR
    - - diagnose rare genetic diseases
      - identify variants in person's DNA
        
        help prevent disease or risk
        
        born baby
        
        screening
        
        30 different genetic conditions
      - vaccine production
        
        prevent various infectious diseases
    - - help doctors
        
        reduce symptoms
        
        increase life expectancy
  - - - huge difference for patients
        
        find support w/ people similar diagnosis
- - - - Treatments
        
        applied to
        
        produce human growth hormones
        
        follicle stimulating hormones (infertility)
        
        human albumin
        
        monoclonal antibodies
    - - polymerase chain reacion
        
        Denaturation
        
        heated to 95°C
        
        separated two pieces single-stranded DNA
        
        each strand = template, new strand built
        
        strand separation
        
        Annealing
        
        primer binding
        
        taq polymerase builds 2x new DNA strands
        
        duplication original DNA
        
        new molecules contain one new, one old strand
        
        new strands used for new copies (2x)
        
        temp reduced 55°C>
        
        Extension
        
        New DNA synthesis
        
        temp raised 72°C
        
        number copies doubles after each cycle
        
        20-30 cycles produce sufficient # DNA
      - developed 1983, KARY B. MULLIS
      - why is good
        
        cheap
        
        time efficient - 1-2 hours
        
        lots of copies made
        
        aids
        
        various experiments
        
        molecular biology procedures
        
        forensic analysis
        
        evolutionary biology
        
        medical diagnostics
        
        used to
        
        diagnose genetic disease
        
        detect low levels viral infection
      - used to make lots of copies> specific segment DNA
        
        based on natural processes of cell replication
        
        amplifies DNA to use for electrophoresis
    - - analyse genetic r/ship
        
        different length DNA fragments
        
        smaller DNA = move faster, bigger DNA = slower
        
        pores act as a sieve
        
        compare DNA fragments
      - Steps/process
        
        specific dye and UV light used
        
        green
      - CFTR has deletion
        
        therefore smaller
        
        faster movement through gel
      - aids diagnosis
      - steps
        
        1.
        
        sample placed in the gel semisolid matrix
        
        different racks
        
        comparison
        
        2.
        
        exposure to electric current
        
        longer = slower
        
        shorter = faster
        
        3.
        
        sample viewing
        
        dye & UV
        
        ladders on side determine lengths etc
        
        electrical current used > move molecules through gel
        
        mutated genes are longer/shorter
        
        show up differently when compared to normal
      - separation based on size and electrical charge
      - positive and negative charged side chains of proteins = behave amino acids in electrical field
    - - Gene editing
        
        Types
        
        CRISPR/Cas 9
        
        DNA splicing and insertion
        
        Steps
        
        1.
        
        parts cell introdued
        
        2.
        
        activation enzyme by RNA guide
        
        3.
        
        enzyme unwind DNA
        
        4.
        
        repair template used
        
        inexpensive, versatile
        
        Cas9 (enzyme)
      - vetctors
        
        viruses
        
        liposomes
        
        difficulty to penetrate membrane
        
        lungs natural defense mechanism
      - defective genes replaced to treat genetic disorders
      - benefits
        
        works w/ any individual
        
        prevents further damage, reduce symptom
      - Non-integrating
        
        piece DNA correct copy CFTR = placed indvdl cell
        
        DNA = separate from genome
        
        gene therapy = no genome, cell = use new copy CFTR to make normal ones
        
        not permanent
        
        last several weeks or few months
        
        repeated treatment for efficiency
      - Integrating
        
        new DNA w/ correct CFTR =delivered indvdl's cells
        
        new copy = put in genome
        
        permanent
        
        limited control on where CFTR goes into genome
    - - PGD
        
        pre-implantation genetic diagnosis
        
        genetic profiling embryo IVF
        
        prior to transfer into uterus
        
        normal development
        
        aids ppl risk at passing genetic conditions to kids
        
        sex-linked and autosomal conditions
        
        embryos w/o genetic condition
        
        transferred to uterus
        
        lowering allelic frequency of condition