2804NRS · Human Pathophysiology And Pharmacology 1
Genetics and Ageing
Disease can be written into the genome (inherited or mutated) and then shaped by time (ageing) — and each half reduces to one diagram. Genetics asks which allele(s) must you inherit to be affected?, read straight off a Punnett square: autosomal dominant (one allele suffices — Huntington's), autosomal recessive (two needed, carriers unaffected — cystic fibrosis), and X-linked recessive (males affected more — haemophilia). It also distinguishes chromosomal disorders (Down = trisomy 21) from single-gene ones, and gain vs loss of function (ties back to cancer). Ageing asks how does an older body handle a drug differently?, read off the ADME spine — with falling renal excretion the headline change, giving the rule 'start low, go slow.' In 2804NRS this is Module 6 — examined by MCQ and short-answer.
What this chapter covers
- 016.1 Chromosomes, genes & the genetic basis of disease
- 026.2 Mendelian inheritance — reading the Punnett square
- 036.3 Ageing physiology — the body over time
- 046.4 Pharmacokinetics in the older adult
Punnett square read-off — two carrier parents
- +1Set up the cross: Aa × Aa — put A and a along the top, A and a down the side, and fill each cell.
- +1Genotype ratio: 1 AA : 2 Aa : 1 aa (1:2:1).
- +1Phenotype ratio: 3 dominant : 1 recessive (only aa shows the recessive condition).
- +1Probabilities: 25% affected (aa), 50% unaffected carriers (Aa), 25% unaffected non-carriers (AA).
Key terms
- Autosomal dominant
- One mutant allele suffices to show the condition; affects both sexes; about 50% offspring risk. Examples: Huntington's disease, achondroplasia.
- Autosomal recessive
- Two mutant alleles are needed; heterozygous carriers (Aa) are unaffected but can pass the allele on. Examples: cystic fibrosis, Tay-Sachs.
- X-linked recessive
- The gene sits on the X chromosome, so males (single X) are affected far more often; females are usually carriers. Example: haemophilia.
- Aneuploidy / trisomy
- An abnormal chromosome NUMBER; trisomy means one extra chromosome. Down syndrome is trisomy 21 — a whole-chromosome change, not a single-gene defect.
- Ageing pharmacokinetics
- Age shifts every ADME step the same way — drug levels rise and half-life lengthens. Falling renal excretion (GFR) is the biggest effect, giving the prescribing rule 'start low, go slow.'
Genetics and Ageing FAQ
How do I read an inheritance pattern from a cross?
Use a Punnett square: capital = dominant allele, lower-case = recessive. For two carriers (Aa × Aa) the genotypes are 1 AA : 2 Aa : 1 aa and the phenotypes 3 dominant : 1 recessive — so 25% affected, 50% carriers. Autosomal dominant needs one allele, autosomal recessive needs two, and X-linked recessive hits males more often.
Is a carrier the same as being affected?
No. A carrier (Aa) is heterozygous and unaffected but can pass the recessive allele to children. A recessive condition only shows when both copies are faulty (aa). Confusing carrier with affected is a common MCQ trap, as is forgetting that X-linked recessive disease affects males far more than females.
What is the difference between a chromosomal and a single-gene disorder?
A chromosomal disorder is a change in chromosome number or structure — Down syndrome is trisomy 21, a whole extra chromosome. A single-gene disorder is a point mutation in one gene — cystic fibrosis, Huntington's and haemophilia. Calling Down syndrome a single-gene defect is a classic error.
Which pharmacokinetic change matters most in the elderly?
Reduced renal excretion (falling GFR) is the dominant change and the main reason older patients accumulate drugs to toxic levels — especially renally cleared, narrow-therapeutic-index drugs like digoxin, gentamicin and lithium. The safe principle is 'start low, go slow': a lower dose, titrated slowly, with monitoring.
Exam move
Make the Punnett-square read-off automatic — the Aa × Aa cross (1:2:1 genotype, 3:1 phenotype, 25% affected, 50% carriers) is a guaranteed item, and the high-value distinction is carrier (unaffected) vs affected. Lock in the three inheritance patterns with one example each, and keep chromosomal (Down = trisomy 21) separate from single-gene. For ageing, lay the changes onto the ADME spine and remember that renal excretion is the biggest effect, giving 'start low, go slow' — compounded by low albumin (more free drug) and polypharmacy.
