Linkage mapping

Linkage

Linked and unlinked loci

When two genes (or a gene and a marker, or two markers) are situated closely together on a chromosome, they often inherit together: their loci are linked. Diploid organisms have two sets of chromosomes: one set from the father and one set from the mother. Two similar chromosomes are called homologues. Homologous chromosomes (or 'homologues') are chromosomes that are similar, but not identical. They carry genes for the same traits, but they can have different alleles for those genes.

In the figure below, the loci A and B are linked, since they are situated in the same region of a chromosome. There are two situations for the breeder. Suppose the breeder prefers allele A and allele B, but not alleles a and b. The figure shows that A and B can be present on the same parental chromosome (left picture). This situation is called coupling phase. He is lucky. In the right hand picture he would like to combine A and B, which are on different homologues. This is called repulsion phase. These terms are also used in case A and B represent the dominant alleles of genes or markers instead of the desired alleles or when referring to two specific marker alleles or alleles of genes being on the same or on different homologues.

The picture shows two individuals carrying one chromosome from the mother (red) and one from the father (blue). The red and blue chromosomes are homologues of each other. They contain two linked loci, A and B, and each locus exists in two variants (alleles), indicated here as A and a, and B and b. Left: Alleles A and B are linked in coupling phase, and A and b in repulsion phase. Right: Alleles A and b are linked in coupling phase, and A and B in repulsion phase. The two loci are linked; the alleles are in coupling or repulsion phase.

Suppose that alleles A and B are favorable. In that case, the ideal genotype AABB can be obtained easily in the case of linkage of A and B in coupling phase (left): if the two loci are (closely) linked, selection for A will almost always also bring allele B to the same progeny (it requires only non-recombinant gametes). If the alleles are linked in repulsion, however, (right picture), it will be hard to obtain AABB, since they occur on two different homologous, so it requires a recombination event, in both gametes, between A and b to bring A and B together. 

 Show/hide comprehension question...

 Show/hide comprehension question...

When genes are located on different (non-homologous) chromosomes, they inherit independently (see figure below). The process involved is called independent assortment of chromosomes. Whether a gamete receives homologue 1 or 2 of chromosome 1 has no relation with whether this gamete receives homologue 1 or 2 of chromosome 2. Genes on different chromosomes are always unlinked and their inheritance is independent.

Independent assortment of chromosomes during meiosis results in random distribution of chromosomes per homologous pair. For example, a gene located on Chromosome 1 is not linked with a gene on Chromosome 2, and hence they are distributed independently from each other during meiosis. The chance for A and B ending up in the same gamete is as large as the chance for A ending up with b.

During a cross-over, homologous parts are exchanged, resulting in intrachromosomal recombination (= recombination within the chromosome between the homologues; see figure below).

The meiosis depicted above will result in gametes AB, aB, Ab and ab. Of these, the aB and Ab gametes are novel (non-parental) combinations, hence the term 'recombination'.

Note that recombination only results in new allele combinations when homologues carry different alleles on both loci: both should be heterozygous (double heterozygous). If between loci A and B there are other sequence differences between the two parents, these will also form new combinations.

Cross-over

When genes or markers are located together (on the same chromosome), they are called 'linked'. The shorter the distance between them, the lower the chance for a cross-over taking place between them. Alleles of closely linked loci tend to inherit together, because the probability of a crossover event in between the two loci is rather small.

A linkage group is a statistically defined group of genes/markers that are significantly associated. This association is usually ascribed to physical linkage of their loci on the chromosome. In theory, a linkage group comprises all loci on an entire chromosome. The linear linkage of the loci causes the genes and markers to be linked to each other, and to inherit in association. However, in practice, linkage is not always statistically shown, e.g. because of large gaps due to insufficient markers or non-polymorphic chromosome regions.

Genes (or a gene and a marker) that are located on the same chromosome, but far away from each other (like A and J in the picture below), behave as if they were unlinked. This is because, during meiosis, in the paired homologous chromosomes

there is such a high probability for one or more recombinations to occur, that in case of A-a/J-j polymorphism, A will roughly occur equally frequent with the linked J (gamete AJ) as with the alternative j (gamete Aj).

Summary

→    Genes/markers are linked if they are located closely together on the same chromosome

→    Gene/marker alleles can be linked in coupling phase (on the same homologue) and in repulsion phase (on different homologues)

→    Independent assortment of chromosomes is the mechanism for non-homologous chromosomes to recombine

→    Cross-over is the mechanism for homologous chromosomes to recombine

→    A linkage group is a statistically defined group of genes/markers that are significantly associated

→    New combinations of alleles of (linked and unlinked) genes can only arise if those genes were both present in a heterozygous state.

 

I want an alternative explanation | Move on to: Linkage, recombination and map distance