Mendelian Inheritance Patterns
On this page
Direct answer
One mutated allele is enough for disease in autosomal dominant (AD) inheritance — vertical transmission, male-to-male passage possible, 50 per cent offspring risk — while autosomal recessive (AR) disease needs both alleles, skipping generations and clustering where consanguinity is common — uncle-niece and first-cousin marriages in parts of south India raise AR disease several-fold. X-linked recessive traits (haemophilia A, Duchenne dystrophy, G6PD deficiency) strike carrier mothers' sons through oblique transmission with no male-to-male passage; X-linked dominant traits are rarer and lethal in males prenatally in some (Rett syndrome); mitochondrial inheritance passes only from mothers, to variable proportions of offspring, with severity set by heteroplasmy. Beyond strict Mendelism lie anticipation (expanding trinucleotide repeats in Huntington and myotonic dystrophy), imprinting (the same 15q11-13 deletion causing Prader-Willi from the father and Angelman from the mother), and reduced penetrance and variable expressivity explaining affected and unaffected carriers in one pedigree.
What you must remember
- Autosomal dominant anchors: Huntington disease, Marfan syndrome (FBN1), achondroplasia (FGFR3, typically new paternal mutations with advanced paternal age), familial hypercholesterolaemia (LDLR — the commonest AD lethal in heterozygotes), hereditary spherocytosis, polycystic kidney disease.
- Autosomal recessive anchors: sickle cell anaemia, cystic fibrosis, phenylketonuria, congenital adrenal hyperplasia, spinal muscular atrophy, beta thalassaemia major — Indian carrier frequency for beta thalassaemia trait is roughly 3-4 per cent, higher in Sindhi, Punjabi and Gujarati communities.
- X-linked recessive anchors: haemophilia A and B, Duchenne and Becker dystrophy (same DMD gene, in-frame versus out-of-frame deletions), G6PD deficiency, red-green colour blindness, Lesch-Nyhan.
- X-linked dominant and Y-linked: vitamin D-resistant rickets (hypophosphataemia) and Rett (MECP2, de novo, lethal in males); Y-linked traits pass father to all sons — hairy ears the textbook curiosity.
- Mitochondrial pedigree rules: maternal transmission only, all children of an affected mother may be affected, none of an affected father; heteroplasmy and threshold effect explain intrafamilial variability; MELAS, MERRF, LHON, Kearns-Sayre.
- Trinucleotide repeat disorders: polyglutamine (CAG) — Huntington above 36 repeats, spinocerebellar ataxias; expansion of non-coding repeats — myotonic dystrophy CTG, fragile X CGG more than 200 (full mutation), Friedreich GAA; anticipation is worse with maternal transmission in myotonic dystrophy and paternal in Huntington.
- Imprinting pair to memorise: paternal 15q deletion or maternal uniparental disomy gives Prader-Willi (hypotonia, obesity, hyperphagia, hypogonadism); maternal deletion or paternal disomy gives Angelman (puppet gait, seizures, absent speech).
Drawing the pedigree in the exam
Approach any pedigree question with three passes. First, count generations: vertical transmission across every generation with both sexes affected suggests AD; affected siblings with unaffected parents, or consanguinity, suggests AR. Second, follow the sex pattern: only males affected, linked through unaffected mothers and never father-to-son, is X-linked recessive; a trait where affected fathers pass it to all daughters and no sons is X-linked dominant. Third, look for the non-Mendelian signature: transmission exclusively through the maternal line to children of both sexes is mitochondrial, and progressively earlier or severer disease down generations is anticipation. Now apply it: a Kerala family with several members dying of renal failure in their fifties, transmitted father to son, is autosomal dominant polycystic kidney disease — male-to-male passage itself excludes X-linkage. A child with self-mutilation whose maternal uncles were similarly affected points to Lesch-Nyhan; a sibling-only pattern with parental consanguinity argues AR — thalassaemia or sickle cell tops that list regionally.
Where candidates slip
Two errors dominate. First, equating "skips a generation" with AR — reduced penetrance in AD disorders, such as hereditary haemochromatosis or polydactyly, also produces skipped generations, so check the pattern across the whole pedigree rather than one gap. Second, forgetting that X-linked dominant disorders affect both sexes, so bilateral, male-to-male-excluding distribution with both sexes involved is not automatically AD — vitamin D-resistant rickets is the exam's favourite counterexample. A third subtlety: isolated cases of achondroplasia or osteogenesis imperfecta type II with unaffected parents are usually new paternal mutations, not non-paternity. And in anticipatory disorders, always state the parent of origin: a grandfather with late-onset Huntington, an earlier-onset father, and a childhood-onset son is the classic three-generation vignette.
Frequently asked questions
Why does consanguinity increase autosomal recessive disease?
Related parents share alleles from a common ancestor, so the chance both carry the same rare recessive mutation rises several-fold, making AR conditions cluster in consanguineous pedigrees.
How is mitochondrial inheritance recognised on a pedigree?
An affected mother transmits to a variable proportion of sons and daughters, an affected father to none; heteroplasmy means severity differs among offspring carrying the same mutation.
What is genetic anticipation and which disorders show it?
Earlier onset and greater severity in successive generations due to trinucleotide repeat expansion, classically Huntington disease and myotonic dystrophy, worse with paternal transmission in Huntington and maternal in myotonic dystrophy.
How can one 15q11-13 deletion cause two different syndromes?
Genomic imprinting: loss of the paternally expressed genes causes Prader-Willi syndrome, loss of the maternally expressed UBE3A causes Angelman syndrome, from deletion of the same region or uniparental disomy.
Why do Duchenne and Becker dystrophy differ despite sharing a gene?
Both are X-linked DMD mutations, but out-of-frame deletions truncate dystrophin completely causing Duchenne, while in-frame deletions preserve a partly functional protein causing the milder Becker phenotype.