Autosomal Linkage

AQA spec ref: 3.7.1 - Inheritance

Mendel's Law of Independent Assortment states that alleles of different genes assort independently during meiosis. This holds when genes are on different chromosomes. But humans have ~20,000 genes distributed across only 23 chromosome pairs, so many genes must share the same chromosome. Genes that share a chromosome are linked genes, and they tend to be inherited together, violating Mendel's prediction. Understanding linkage is essential for interpreting inheritance data and for connecting genetics to evolutionary biology.

What Linkage Actually Means

Think of each chromosome as a long sequence of genes. If two genes sit on the same chromosome, they will generally be pulled into the same gamete during meiosis I - they travel as a unit. This means the parental combinations of alleles (the combinations that existed in the parent) appear far more frequently in offspring than recombinant combinations (new combinations formed by crossing over).

Example: genes A and B are on the same chromosome. The parent has genotype AB/ab (one homologue carries A and B alleles together; the other carries a and b alleles together). If the genes were on different chromosomes (independent assortment), the four gamete types AB, Ab, aB, ab would each appear at 25%. But because A and B are linked, gametes AB and ab (parental types) appear much more often than Ab and aB (recombinant types).

Recombination: The Exception to Linkage

Linkage is not absolute. During prophase I of Meiosis, homologous chromosomes pair up (forming bivalents) and non-sister chromatids exchange segments at points called chiasmata - this is crossing over. Crossing over reshuffles alleles between the two homologues, producing recombinant chromosomes.

The further apart two genes are on a chromosome, the more likely a chiasma will occur between them - therefore the higher the probability of recombination. Genes very close together are rarely separated by crossing over; genes far apart (or on different chromosomes) assort nearly independently.

Recombination Frequency and Genetic Maps

Recombination frequency (RF) is:

• RF < 50% → genes are linked (on the same chromosome)
• RF = 50% → genes behave as if unlinked (either on different chromosomes, or so far apart that crossing over between them is virtually certain)

RF also measures genetic distance: 1% RF = 1 centimorgan (cM) = 1 map unit. By measuring RF between multiple pairs of genes, a linkage map can be constructed showing the relative order and spacing of genes along a chromosome.

How to Detect Linkage: The Test Cross

To measure recombination frequency, a test cross is used: cross the organism with unknown gamete ratios against a homozygous recessive individual (aabb). Because the test cross parent contributes only ab gametes, the phenotype of each offspring directly reveals which gamete the dihybrid parent produced.

Worked Example:

A test cross of an AaBb organism (with A and B linked in coupling: AB/ab) × aabb gives:

Recombinant offspring = 75 + 75 = 150.

The two genes are 15 cM apart on the same chromosome. The signature of linkage is clear: parental classes (430 + 420 = 850) vastly outnumber recombinant classes (150).

Explaining the Data - AQA Mark Scheme Language

When explaining why parental combinations are more frequent, say:

• "The two genes are located close together on the same chromosome"
• "Crossing over between the two loci is less frequent than no crossing over" (because a chiasma must form at precisely the right point)
• "Therefore parental combinations are preserved in most gametes"

Simply saying "the genes are linked" without explaining why this leads to unequal ratios will not get full marks.

Repulsion vs Coupling

Coupling (cis): the two dominant alleles are on the same homologue (AB/ab). Parental classes = AB and ab. Recombinant = Ab and aB.

Repulsion (trans): the two dominant alleles are on different homologues (Ab/aB). Parental classes = Ab and aB. Recombinant = AB and ab.

It is important to identify which parental combination the original organism had, to correctly identify parental vs recombinant gametes. The parental classes are always the most frequent.

The Broader Significance of Linkage

Linkage is directly relevant to population genetics and genomics. Disease-associated alleles often exist in haplotype blocks - stretches of DNA inherited together due to linkage. This is why certain single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk (e.g. near TCF7L2) are found together in populations: they are close enough on the chromosome that recombination rarely separates them. Natural selection (or founder effects) on one variant thus drags neighbouring variants along - a phenomenon called linkage disequilibrium. This is crucial for understanding the elevated metabolic disease risk in South Asian populations, where certain haplotype blocks at metabolic disease loci are at higher frequency.

Summary

• Linked genes are on the same chromosome and tend to be inherited together
• Parental combinations appear more often than recombinant combinations
• Recombination occurs via crossing over at chiasmata in prophase I of meiosis
• RF = recombinant offspring / total offspring × 100%; RF < 50% = linked
• 1% RF = 1 cM = 1 map unit of genetic distance
• Test cross detects linkage by directly revealing gamete types
• Coupling (AB/ab) vs repulsion (Ab/aB): identify parental type first, then classify recombinants

AQA Exam Tips

• Calculate RF: always show formula and working. Express as a percentage. If RF < 50%, conclude genes are linked.
• Identifying parental vs recombinant classes: the parental classes are always the most frequent. Identify which combination of alleles the parent had, then any offspring that carry new combinations are recombinants.
• Why parental classes dominate: "crossing over between the two loci occurs less frequently than no crossing over because the loci are close together on the same chromosome." State this explicitly.
• The 9:3:3:1 vs linkage ratio: if a dihybrid cross gives a ratio close to 9:3:3:1, genes are unlinked. If parental classes are far more frequent, genes are linked. AQA will give you numbers and ask you to decide.
• Test cross is needed: you cannot easily distinguish linkage from independent assortment using F2 data alone (because dominance masks some genotypes). The test cross reveals gamete types directly.
• Map units: give genetic distance as a percentage (cM). "The genes are 15 map units apart" or "15 cM apart."