Mendelian Inheritance, Linkage, and Pedigree Analysis
Classical transmission genetics in modern form
Segregation and assortment
Mendelian inheritance describes how alleles segregate during meiosis and combine at fertilization. In practice, observed ratios are modified by sampling variation, lethal alleles, reduced penetrance, variable expressivity, imprinting, and linkage.
Pedigree vocabulary
Linkage and recombination
Linkage analysis infers locus proximity from co-segregation patterns. Recombination is not uniform: hotspots, cold spots, sex differences, chromosomal structure, and interference all shape the map. Classical linkage remains valuable for rare-variant disease mapping and family-based discovery.
Useful modeling habit
When pedigree data look inconsistent with a simple dominant or recessive model, ask first about penetrance, de novo mutation, phenocopies, and ascertainment bias.
Interpreting a pedigree
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1
Identify the inheritance pattern: autosomal dominant, autosomal recessive, X-linked, mitochondrial, or complex.
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2
Look for sex bias, skipped generations, consanguinity, and affected-parent transmission.
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3
Consider incomplete penetrance, reduced fertility, and variable expressivity.
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4
Test the model with recombination and molecular data where available.
A trait appears in every generation, affects both sexes equally, and an affected parent has about half of offspring affected. The best first model is:
Vertical transmission across generations with roughly 50% affected offspring from an affected heterozygous parent is consistent with autosomal dominant inheritance.
Correct answer: Autosomal dominant inheritance
What does a recombination fraction of 0.1 suggest about two loci?
A recombination fraction below 0.5 indicates linkage; for small distances, 1% recombination is approximately 1 centimorgan.
Correct answer: They are linked and approximately 10 centimorgans apart, though interference and multiple crossovers can affect the estimate.
Mendelian and non-Mendelian transmission
Mendelian-like
- Clear segregation patterns
- Often single-locus or oligogenic
- Useful in pedigree-based mapping
Non-Mendelian
- Imprinting, mitochondrial inheritance, meiotic drive, mosaicism
- Ratios deviate from simple expectations
- Requires mechanistic explanation beyond allele segregation
Which factor can make a dominant trait appear to skip a generation?
If an individual carries the causal genotype but does not express the phenotype, the trait can appear to skip generations.
Correct answer: Incomplete penetrance