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Genetics Unit 4: Linkage Mapping and Recombination
Genes on the same chromosome are linked, and the frequency of recombination between them can be used to build genetic maps and predict the gametes they form.
Covers: Recombination frequency and map units, Coupling and repulsion phase, Two-point test crosses, Three-point crosses and gene order, Double crossovers and interference, Linkage in humans and LOD scores
Study guide
Genes on the same chromosome tend to be inherited together, but crossing over in prophase I can separate them. Offspring that carry the allele combinations of the parent's original chromosomes are parental; those with new combinations are recombinant. In a test cross to a homozygous recessive, the offspring phenotypes reveal the heterozygote's gametes directly, so recombination frequency (RF) = recombinant offspring / total. Sturtevant realized that RF reflects distance: genes farther apart are more likely to have a crossover between them. One map unit, or centimorgan (cM), equals 1% recombination.
Before counting recombinants, determine the phase of the heterozygote. In coupling (cis), AB/ab, the dominant alleles are together; in repulsion (trans), Ab/aB, they are on different homologs. The two most common test-cross classes are always parental and reveal the phase. Each recombinant gamete type is half of RF, and each parental type is (1 − RF)/2. These gamete frequencies let you predict any cross, including selfing: the double recessive fraction is (frequency of ab gametes)², which is large in coupling and small in repulsion.
Recombination frequency cannot exceed 50%. Crossing over happens at the four-chromatid stage, and when genes are far apart, multiple crossovers make recombinant and parental gametes equally likely. Genes on the same chromosome that are very far apart therefore behave as if unlinked. A related problem is that double crossovers between two distant markers restore the parental combination, so two-point crosses underestimate long distances. Maps are most accurate when built by adding up short intervals.
A three-point test cross maps three genes at once. The steps: identify the two largest classes (parental) and the two smallest (double crossovers). The middle gene is the one whose allele differs between a parental class and a double-crossover class. Then, for each interval, add all classes recombinant in that interval, including the double crossovers, and divide by the total. Finally, compare observed double crossovers to expected (product of the two interval RFs × total). The coefficient of coincidence c = observed/expected, and interference I = 1 − c. Positive interference means one crossover discourages another nearby.
Humans cannot be test crossed, so linkage is studied in pedigrees using DNA markers. The LOD score compares the likelihood of the data under linkage at some RF with the likelihood under no linkage, as a base-10 logarithm. A LOD of 3 or more (1000:1 odds) is taken as evidence of linkage. Once a disease gene is linked to a marker and the phase in a family is known from earlier generations, the marker can predict whether a child inherited the disease allele, with an error rate equal to the RF between them.
Key ideas
- Recombination frequency = recombinants / total, and 1% = 1 cM.
- The most common test-cross classes are parental and reveal coupling or repulsion phase.
- Observed recombination cannot exceed 50% because of multiple crossovers.
- In a three-point cross, the gene that switches in double crossovers is in the middle.
- Each interval's distance includes the double crossovers.
- Interference I = 1 − observed/expected double crossovers.
- Human linkage uses LOD scores, with LOD ≥ 3 as the usual threshold.
Formulas and rules
Common mistakes
- Assuming the heterozygote is in coupling without checking which classes are most common.
- Leaving double crossovers out of the interval distance counts.
- Adding the two interval frequencies instead of multiplying them to get expected double crossovers.
- Using half of RF for both recombinant classes combined.
- Treating a 50% recombination frequency as proof that genes are on different chromosomes.
Before the test, make sure you can
- Calculate recombination frequency and map distance from test-cross data.
- Determine coupling or repulsion phase from test-cross counts.
- Predict gamete and offspring frequencies for linked genes.
- Find gene order in a three-point cross from double-crossover classes.
- Calculate interval distances including double crossovers.
- Calculate expected double crossovers, coefficient of coincidence and interference.
- Explain why recombination cannot exceed 50% and why long distances are underestimated.
- Interpret a LOD score.
Words to know
- Linked genes
- Genes located close together on the same chromosome that tend to be inherited together.
- Parental type
- An offspring or gamete with the allele combination of one of the parent's homologs.
- Recombinant type
- An offspring or gamete with a new combination of alleles produced by crossing over.
- Recombination frequency
- The proportion of recombinant offspring among the total.
- Map unit (centimorgan)
- The distance giving 1% recombination.
- Coupling (cis)
- Arrangement AB/ab, with dominant alleles on the same homolog.
- Repulsion (trans)
- Arrangement Ab/aB, with dominant alleles on different homologs.
- Three-point test cross
- A test cross of a triple heterozygote used to find gene order and distances.
- Double crossover
- Two crossovers in the same region, swapping only the middle segment.
- Coefficient of coincidence
- Observed double crossovers divided by expected double crossovers.
- Interference
- The reduction of crossovers near another crossover; I = 1 − c.
- Genetic map
- The order and relative distances of genes based on recombination.
- LOD score
- A base-10 log of the odds of linkage versus no linkage.
- Molecular marker
- A DNA variant at a known location used to follow chromosome segments in families.
Sample practice questions
30 more questions like these, from level 1 to 5, are in the practice set.
One map unit (centimorgan) corresponds to:
- One crossover per chromosome per meiosis
- A physical distance of exactly 1 million base pairs
- A recombination frequency of 1%
- A recombination frequency of 10%
Show the answer and steps
Answer: C) A recombination frequency of 1%
- Map distances are defined from recombination data.
- 1 map unit = 1% recombinant offspring.
- The link to physical distance in base pairs varies by species and region, so it is not a fixed definition.
Why can recombination frequency between two genes never exceed about 50%?
- Even many crossovers between distant genes produce recombinant and parental gametes equally
- Genes on the same chromosome cannot recombine at all
- Any gamete with more than 50% recombinant chromosomes fails to survive
- Crossing over occurs only once per cell, in one chromatid
Show the answer and steps
Answer: A) Even many crossovers between distant genes produce recombinant and parental gametes equally
- Crossing over occurs at the four-strand stage, involving two of four chromatids.
- With many crossovers between two distant genes, half of gametes end up recombinant on average.
- So distant genes look unlinked, with a 50% maximum.
Which gene is in the middle? A heterozygous female is test crossed to an abc/abc male, giving 1000 offspring by phenotype: AbC 390, aBc 400, abC 60, ABc 70, Abc 40, aBC 30, ABC 4, abc 6.
- C
- A
- B
- It cannot be determined without a second cross
Show the answer and steps
Answer: C) B
- Parental classes (most common) are AbC and aBc; double crossovers (rarest) are ABC and abc.
- Compare a double crossover with a parental: AbC versus ABC differ only at B.
- The gene that switches in double crossovers is the middle gene, so the order is A–B–C.