Revision summary
Single-gene disorders chiefly arise from a pathogenic variant at one locus. Autosomal recessive examples include sickle-cell disease, PKU and cystic fibrosis. Autosomal dominant examples include Huntington disease and achondroplasia. Haemophilia A and Duchenne muscular dystrophy are X-linked recessive. Allison linked sickle-cell carrier advantage with malaria. Penetrance, expressivity, new mutations and environment prevent simplistic genetic determinism.
Model answer
Introduction
A single-gene disorder arises mainly from a pathogenic variant at one locus and therefore tends to show a recognisable Mendelian pedigree. Its expression can still vary with penetrance, modifier genes, environment and reproductive fitness.
Body
Major inheritance patterns
- Autosomal recessive: disease usually appears in homozygotes while heterozygotes are carriers. Sickle-cell disease results from a missense variant in HBB; phenylketonuria commonly involves PAH; cystic fibrosis involves CFTR. Sickle-cell heterozygote advantage in malarial regions, identified by A. C. Allison, connects mutation to natural selection.
- Autosomal dominant: one altered allele can suffice. Huntington disease is caused by a CAG-repeat expansion in HTT and often appears after reproduction; achondroplasia commonly involves FGFR3 and many cases are new mutations.
- X-linked recessive: males are more often affected because they have one X chromosome. Haemophilia A involves F8, and Duchenne muscular dystrophy involves DMD. Carrier mothers transmit risk; fathers do not pass X-linked traits to sons.
- X-linked dominant and mitochondrial: these are single-locus patterns too, though the latter is cytoplasmic. Mitochondrial disorders pass through mothers, not affected fathers.
Founder effect and endogamy can raise particular alleles in small populations, making community-sensitive screening useful in India. Yet “one gene” does not mean one fixed outcome: variable expressivity, incomplete penetrance and allelic heterogeneity complicate counselling. Chromosomal syndromes such as Down syndrome are not single-gene disorders.
Flow diagram
flowchart TD M[Single-gene mutation] --> AR[Autosomal recessive] M --> AD[Autosomal dominant] M --> XL[X-linked] M --> MT[Mitochondrial] AR --> SC[Sickle cell / PKU] AD --> HD[Huntington / achondroplasia] XL --> H[Haemophilia / DMD]
Conclusion
Single-gene disorders make Mendelian rules visible in human pedigrees, while sickle cell demonstrates their evolutionary ecology. Diagnosis should combine pedigree and molecular evidence without converting communities into genetic stereotypes.
Quick related
Students also ask
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What is a multifactorial trait? Illustrate your answer with suitable human examples.
Next question on this syllabus topic (2024 · Q7(b)). View answer →
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Is Down syndrome a single-gene mutation disorder?
No. It usually results from trisomy 21, a chromosomal-number abnormality.
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Does one mutated gene guarantee disease?
Not always. Penetrance, expressivity, allele type, modifiers and environment can alter the phenotype.
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