Free explainer4 min read
Inheritance patterns
Understand the model, recognise it in a stem, separate the look-alikes, then apply it.
Start with the mental model
A family tree, or pedigree, reveals the inheritance pattern of a genetic condition through specific, recognisable clues, before any genetic test is done. A pedigree showing the condition in every generation, affecting both sexes, with clear father-to-son transmission, points to autosomal dominant inheritance: often faster than waiting for a genetic test.
Watch it explainedA pedigree looks like a puzzle. Two questions solve almost all of it.
Visual explanationUse the diagram to rebuild the concept from memory.
01Core model
Autosomal dominant conditions show a vertical pattern through successive generations, affect both sexes, allow male-to-male transmission, and give each child of an affected parent a 50% risk, as in Huntington's disease. Neurofibromatosis type 1 (caused by NF1 mutations on chromosome 17) and Pick's disease/frontotemporal dementia are further named autosomal dominant examples. Autosomal recessive conditions can appear in siblings born to unaffected carrier parents, affect both sexes, may show consanguinity (parents being blood relatives), and give each pregnancy between two carriers a 25% risk. X-linked recessive conditions mainly affect males, show no father-to-son transmission, and an affected father makes all his daughters carriers if the mother is unaffected. Hunter syndrome (mucopolysaccharidosis type II) and Duchenne muscular dystrophy are named X-linked recessive examples. Both can show a skip-generation pedigree, an affected maternal grandfather having an affected grandson through an unaffected carrier daughter, sometimes called the 'knight's move' pattern after the chess piece's diagonal jump across the pedigree. Females carry two X chromosomes, and random X-inactivation (Lyonization) silences one X per cell, producing a functional mosaic. This is why heterozygous carrier females of an X-linked recessive condition are usually unaffected or only mildly affected, unlike hemizygous males who express whichever allele their single X carries. X-linked DOMINANT inheritance is a separate, less common pattern. Like X-linked recessive, an affected father shows no father-to-son transmission and passes the condition to all of his daughters. Unlike X-linked recessive, heterozygous carrier females are themselves affected (transmitting to about half their children of either sex) rather than being unaffected carriers. Rett syndrome, caused by a de novo (new, not inherited from a parent) MECP2 mutation, and Fragile X syndrome (with reduced penetrance, meaning not everyone carrying the mutation shows the full phenotype) are both classed as X-linked dominant. Mitochondrial conditions pass from an affected mother to children of either sex, but never from an affected father. A pedigree where only males are affected, with no father-to-son transmission anywhere, points specifically to X-linked recessive inheritance. E.g., a pedigree with affected males only, skipping generations through unaffected carrier daughters, points to X-linked recessive inheritance. Not every condition is inherited at all: Klinefelter syndrome (47,XXY) arises sporadically from meiotic nondisjunction (a chromosome-separation error during egg or sperm formation), not from a transmitted gene, so it does not follow a Mendelian ratio and is not usually seen recurring in a family.
02Recognise it in an SBA
• A single gene mutation causes lens dislocation, aortic root dilation and long-bone overgrowth in one patient, affecting several unrelated body systems. Which genetic term fits this pattern?
• Retinitis pigmentosa can result from mutations in dozens of different genes, each independently able to cause a similar clinical picture. Which genetic phenomenon does this show?
03Separate the look-alikes
| Autosomal dominant | affected in every generation with about 50% offspring risk, unlike autosomal recessive's skipped generations and 25% risk. Named examples: Huntington's disease, neurofibromatosis type 1 (NF1, chromosome 17), Pick's disease/frontotemporal dementia. |
|---|---|
| Autosomal recessive | two carrier parents give a 25% affected risk, rather than the 50% of dominant inheritance. |
| X-linked recessive | affects males through carrier mothers with no male-to-male transmission, whereas autosomal patterns affect both sexes equally. Named examples: Hunter syndrome, Duchenne muscular dystrophy (the 'knight's move' skip-generation pattern). |
| X-linked dominant | affected males transmit to all daughters and no sons, but unlike X-linked recessive, heterozygous carrier females are affected too (e.g. Rett syndrome/MECP2 de novo, Fragile X with reduced penetrance). |
| X-inactivation mosaicism | random silencing of one X per cell means carrier females of an X-linked recessive condition are usually unaffected or only mildly affected, unlike hemizygous affected males. |
| Mitochondrial inheritance | transmitted only through the mother to all children, unlike nuclear inheritance. |
| Sporadic chromosomal disorders | Klinefelter syndrome arises from meiotic nondisjunction, not Mendelian inheritance, unlike the fixed-ratio patterns above. |