02/05/22
BIOL2211: Human Diseases Revision Notes
W1.1 Genetics & Clinical Management
Aetiology = the cause, set of causes, or manner of causation of a disease or condition.
- Communicable diseases tend to be solely environmental and not dependent on
genetics
Types of genetic disorders:
1. Multifactorial (common)
One organ system affected
Variants in genes cause alteration of function
2. Chromosomal (0.6% live born)
Multiple organ systems can be affected
Chromosomal imbalance causes alteration in gene dosage
3. Single gene (1% live born)
Can affect structural proteins, enzymes, receptors etc
Mutations in single genes often cause loss of function
Down’s syndrome:
Extra chromosome 21, there are 3 patterns of this:
1. Trisomy 21 – 3 separate copies of c21 (95% of people)
2. Robertsonian translocation – can result in extra c21 copy (4% of people)
3. Mosaicism – normal and trisomy cell lines (1% of people)
Down’s syndrome features round face, protruding tongue, developmental delay
Trisomy 13 (Patau syndrome):
- Very poor prognosis, majority of babies die in first few weeks
- Affects 1 in 5000 births
- Multiple malformations: incomplete lobation of brain, cleft lip, congenital heart
defects (CHDs)
Numerical chromosome abnormalities that result in a gain or loss of complete
chromosomes have serious, often lethal consequences.
Non-disjunction in meiosis 1 result of the homologous chromosomes failing to separate
towards the poles during anaphase 1.
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Microdeletions:
Chromosomal region lost, identified using specific molecular cytogenetic techniques.
Example -> DiGeorge syndrome: small mouth, prominent nose, CHDs
Example -> Williams syndrome: bright eyes, wide mouth, flattened nasal bridge
Single genes disorders:
High risks to relatives
Dominant/recessive pedigree
patterns
Some isolated cases due to new
dominant mutations
Affects structural proteins,
enzymes, receptors, transcription
factors etc.
Mitochondrial inheritance: general
mutations in mitochondria can
affect metabolism.
Multifactorial inheritance:
E.g. -> cystic fibrosis: body makes thick, sticky mucus which causes lung problems.
E.g. -> Duchenne muscular dystrophy: progressive muscle-wasting disease that leads
to movement difficulties, muscle of affected people has absence of dystrophin.
Familial hypercholesterolaemia:
Disorder of cholesterol metabolism & is most common inherited metabolic disease
Leads to premature atherosclerosis, cardiovascular death
Main cause is autosomal dominant mutations in LDLR
Phenylketonuria:
Rare inherited disorder which causes build-up of phenylalanine in body
Counteract defect -> restrict diet of phenylalanine
Can result in intellectual disability, epilepsy, impaired melanin synthesis, eye
abnormalities
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W1.2 Genetic Diagnosis
Reasons for diagnostic testing confirm/refute clinical diagnosis, assess carrier status,
prenatal diagnosis, predictive testing
Karyotyping = the process of pairing & ordering all an organism’s chromosomes, thus
providing a genome-wide snapshot of an individual’s chromosomes.
- Chromosomes arranged in descending size
- Each pair of chromosomes distinguished by individual banding pattern
Amniocentesis = a process in which amniotic fluid is removed from uterus for
testing/treatment.
Chorionic villus sampling = prenatal test in which sample of chorionic villi is removed from
placenta for testing.
Chromosomes can be classified by their centromere position:
o Telocentric = centromere located at one end
o Acrocentric = centromere located quite near one end
o Metacentric = centromere located midway between two ends of chromosome
Can also be classified by size, chromomere and heterochromatin patterns, high resolution
band patterns, genes highlighted by DNA probes using fluorescence in situ hybridisation.
FISH = fluorescence in situ hybridisation can be performed on metaphase and interphase
cells, being able to identify structural numerical abnormalities.
o 3 types of FISH probe:
o Repetitive sequences
o DNA segments binding to & covering whole chromosome
o DNA segments from specific genes/regions on chromosome
