Cystic fibrosis
- Diff versions due to diff mutations of CFTR gene
- Affect liver, lungs, pancreas, spleen, skin, reproduction
- Liver and gallbladder: extra sticky bile blocks bile duct > irritation and
inflammation, scar tissue > liver disease
- Lung:
- Excess sticky mucus cause bacterial infection
- Mucus block bronchioles
- Less steep conc gradient, lower rate of gas exchange
- Let air pass in but not out: overinflation of lung tissue,
reduced elasticity
- Airway clearance, antibiotics
- Pancreas: mucus blocks delivery of digestive enzymes to digestive system,
protease break down islets of langerhans, trouble producing insulin and
digestive enzymes > type 1 diabetes
- Pancreatic enzyme pills (gastro-resistant to low pH)
- Need high fat + calorie intake: partial digestion and malabsorption
- Saltier skin: faulty secretory cell of sweat glands, sweat glands cannot
reabsorb salt from sweat
- Reproduction: infertility
- Mucus block vas deferens / congenital bilateral absence of the vas
deferens CBAVD
- thicker vaginal mucus plug, harder for sperm to reach ovum
Endocrine glands Exocrine glands
Pituitary gland, thyroid gland, adrenal glands, Pancreas, salivary glands, gastric glands: sweat,
pancreas: secrete hormones to regulate body tears, saliva, milk and digestive juices
- With ducts >> get blocked by mucus
functions
- Richly supplied w blood capillaries
- Ductless: secrete hormones directly
into blood
Pancreas: endocrine gland regulate blood glucose level by secreting insulin + glucagon into
blood
, ● Also exocrine gland: acinar cells secrete pancreatic juice w digestive enzymes
(pancreatic amylase, proteases, lipase) via pancreatic duct for digestion
Mutations
- Sudden and permanent change in DNA of an organism
Causes of mutations
1. Spontaneous mutations
a. Occur naturally and randomly at a very low rate (esp @DNA replication)
2. Induced mutations by mutagens
a. Chemical: change chemical structure of DNA
i. Nitrous acid (food preservatives): change base of DNA molecule
ii. Tar (cigarette smoke)
iii. Asbestos (construction materials)
iv. Mustard gas (chemical warfare)
b. Radiation
i. UV light (sunlight)
ii. X-rays (medical examination): ionise water or other molecules to form
free radicals (highly reactive, can damage DNA molecules)
, iii. Gamma rays (radiotherapy, nuclear bombs): ionise water or other
molecules to form free radicals (highly reactive, can damage DNA
molecules)
Types of mutations
Gene mutations Chromosome mutations
- Changes in base sequence of DNA - Changes in structure/number of
on a gene chromosomes
- Occur @DNA replication - Occur @
- Produce new alleles in a population
Change in chromosome structure
POINT MUTATION - Affect some genes: death of
Substitution and inversion embryos/foetuses before birth
- usually change in 1 triplet code only - @crossing over of non sister
- Possibilities chromatids in meiotic cell division
a. Silent mutation: new code - Possibilities
specifies the same amino acid: X - Deletion
effect on AA sequence - Duplication: segment is
b. Missense mutation: new code repeated
specifies a diff amino acid: 1 - Inversion: broken segment
diff amino acid: change of protein reversed order, reinserted
structure in non-critical area / - Translocation: crossing over
critical area (alter 3D structure of chromatids of non
of protein> non functional) homologous chromosomes
c. Nonsense mutation: new code
specifies a stop signal: Change in chromosome number
polypeptide production stopped - Addition of loss of many genes per
prematurely > non functional chromosome: most die before birth
- @anaphase I, II in meiotic cell
FRAMESHIFT MUTATION division
Deletion and insertion - Nondisjunction: homologous pair of
- Often dramatic effect chromosomes or sister chromatids
- Possibilities fail to separate, go to same
- Delete/insert Xmul3 bases: daughter cell > abnormal no of
shift reading frame, whole chromosomes
AA sequence after point of
mutation altered > non <extra chromosome 21> down syndrome
functional - Risk increases with mother’s age
- @meiosis: 2 members of homologous
, <substitution> sickle cell anaemia chromosome 21 fail to separate,
- (2 mutated alleles) Substitution of gamete bearing extra chromosome
base in gene coding for polypeptide fuse with normal gamete
chain in haemoglobin: - Symptoms
- base T replaced by base A - Shorter than avg
- 1 diff amino acid (valine - Distinctive round face with
instead of glutamic acid) smaller ears
- affect shape of polypeptide - Some degree of mental
formed, properties of retardation
protein - Most die @early childhood due to
- Low O2 levels: abnormal infections, heart defects
haemoglobin molecules less soluble,
stick tgt, form long fibres, distort <missing X chromosome: XO> turner’s
shape of RBCs (sickle shaped) syndrome
- Decrease O2 carrying - Female
capacity of RBCs - Little development of secondary
- Clump tgt, block capillaries > sexual characteristics
easy bruising, damage organs - Infertile: X ovaries, menstruation
- RBCs have shorter life span
> anaemia <extra X chromosome: XXY> klinefelter’s
syndrome
- Male
- Some degree of breast development
- Infertile: testes underdeveloped
<common: phenylalanine (AA) deletion> cystic fibrosis
- Cystic fibrosis transmembrane regulator (CFTR) non functional / absent
- Transmembrane/integral protein
- Ligand-gated chloride channel: facilitated diffusion
- ATP and phosphate bind to CFTR to open/close gate
- Cl- travel down conc gradient (unidirectional: Cl- leave cell)
- CFTR closed = ENaC always opened
- Epithelial sodium channel (unidirectional: Na+ enter cell)
- >> ATP temporarily builds in cell
- Decreased conductance: X transport Cl- ions out across cell membrane to lower
water potential
- Water and Na+ X move out by osmosis
- Mucus become thick, sticky >> accumulation
- Diff versions due to diff mutations of CFTR gene
- Affect liver, lungs, pancreas, spleen, skin, reproduction
- Liver and gallbladder: extra sticky bile blocks bile duct > irritation and
inflammation, scar tissue > liver disease
- Lung:
- Excess sticky mucus cause bacterial infection
- Mucus block bronchioles
- Less steep conc gradient, lower rate of gas exchange
- Let air pass in but not out: overinflation of lung tissue,
reduced elasticity
- Airway clearance, antibiotics
- Pancreas: mucus blocks delivery of digestive enzymes to digestive system,
protease break down islets of langerhans, trouble producing insulin and
digestive enzymes > type 1 diabetes
- Pancreatic enzyme pills (gastro-resistant to low pH)
- Need high fat + calorie intake: partial digestion and malabsorption
- Saltier skin: faulty secretory cell of sweat glands, sweat glands cannot
reabsorb salt from sweat
- Reproduction: infertility
- Mucus block vas deferens / congenital bilateral absence of the vas
deferens CBAVD
- thicker vaginal mucus plug, harder for sperm to reach ovum
Endocrine glands Exocrine glands
Pituitary gland, thyroid gland, adrenal glands, Pancreas, salivary glands, gastric glands: sweat,
pancreas: secrete hormones to regulate body tears, saliva, milk and digestive juices
- With ducts >> get blocked by mucus
functions
- Richly supplied w blood capillaries
- Ductless: secrete hormones directly
into blood
Pancreas: endocrine gland regulate blood glucose level by secreting insulin + glucagon into
blood
, ● Also exocrine gland: acinar cells secrete pancreatic juice w digestive enzymes
(pancreatic amylase, proteases, lipase) via pancreatic duct for digestion
Mutations
- Sudden and permanent change in DNA of an organism
Causes of mutations
1. Spontaneous mutations
a. Occur naturally and randomly at a very low rate (esp @DNA replication)
2. Induced mutations by mutagens
a. Chemical: change chemical structure of DNA
i. Nitrous acid (food preservatives): change base of DNA molecule
ii. Tar (cigarette smoke)
iii. Asbestos (construction materials)
iv. Mustard gas (chemical warfare)
b. Radiation
i. UV light (sunlight)
ii. X-rays (medical examination): ionise water or other molecules to form
free radicals (highly reactive, can damage DNA molecules)
, iii. Gamma rays (radiotherapy, nuclear bombs): ionise water or other
molecules to form free radicals (highly reactive, can damage DNA
molecules)
Types of mutations
Gene mutations Chromosome mutations
- Changes in base sequence of DNA - Changes in structure/number of
on a gene chromosomes
- Occur @DNA replication - Occur @
- Produce new alleles in a population
Change in chromosome structure
POINT MUTATION - Affect some genes: death of
Substitution and inversion embryos/foetuses before birth
- usually change in 1 triplet code only - @crossing over of non sister
- Possibilities chromatids in meiotic cell division
a. Silent mutation: new code - Possibilities
specifies the same amino acid: X - Deletion
effect on AA sequence - Duplication: segment is
b. Missense mutation: new code repeated
specifies a diff amino acid: 1 - Inversion: broken segment
diff amino acid: change of protein reversed order, reinserted
structure in non-critical area / - Translocation: crossing over
critical area (alter 3D structure of chromatids of non
of protein> non functional) homologous chromosomes
c. Nonsense mutation: new code
specifies a stop signal: Change in chromosome number
polypeptide production stopped - Addition of loss of many genes per
prematurely > non functional chromosome: most die before birth
- @anaphase I, II in meiotic cell
FRAMESHIFT MUTATION division
Deletion and insertion - Nondisjunction: homologous pair of
- Often dramatic effect chromosomes or sister chromatids
- Possibilities fail to separate, go to same
- Delete/insert Xmul3 bases: daughter cell > abnormal no of
shift reading frame, whole chromosomes
AA sequence after point of
mutation altered > non <extra chromosome 21> down syndrome
functional - Risk increases with mother’s age
- @meiosis: 2 members of homologous
, <substitution> sickle cell anaemia chromosome 21 fail to separate,
- (2 mutated alleles) Substitution of gamete bearing extra chromosome
base in gene coding for polypeptide fuse with normal gamete
chain in haemoglobin: - Symptoms
- base T replaced by base A - Shorter than avg
- 1 diff amino acid (valine - Distinctive round face with
instead of glutamic acid) smaller ears
- affect shape of polypeptide - Some degree of mental
formed, properties of retardation
protein - Most die @early childhood due to
- Low O2 levels: abnormal infections, heart defects
haemoglobin molecules less soluble,
stick tgt, form long fibres, distort <missing X chromosome: XO> turner’s
shape of RBCs (sickle shaped) syndrome
- Decrease O2 carrying - Female
capacity of RBCs - Little development of secondary
- Clump tgt, block capillaries > sexual characteristics
easy bruising, damage organs - Infertile: X ovaries, menstruation
- RBCs have shorter life span
> anaemia <extra X chromosome: XXY> klinefelter’s
syndrome
- Male
- Some degree of breast development
- Infertile: testes underdeveloped
<common: phenylalanine (AA) deletion> cystic fibrosis
- Cystic fibrosis transmembrane regulator (CFTR) non functional / absent
- Transmembrane/integral protein
- Ligand-gated chloride channel: facilitated diffusion
- ATP and phosphate bind to CFTR to open/close gate
- Cl- travel down conc gradient (unidirectional: Cl- leave cell)
- CFTR closed = ENaC always opened
- Epithelial sodium channel (unidirectional: Na+ enter cell)
- >> ATP temporarily builds in cell
- Decreased conductance: X transport Cl- ions out across cell membrane to lower
water potential
- Water and Na+ X move out by osmosis
- Mucus become thick, sticky >> accumulation
