ABSTRACT

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Definition

Linkage is the tendency for alleles of different genes to be passed together from one generation to the next. Only genes situated on the same chromosome can show linkage. A series of alleles on a single homologous chromosome is referred to as a haplotype. Genes on nonhomologous chromosomes are, by definition, unlinked and always show 50% recombination. Parental gametes carry the same set of alleles as were inherited together from one parent. Recombinant gametes carry alleles derived from both parents. The degree of linkage between two genes depends on the frequency of crossovers that occur between them during meiosis. The closer they are together the less likely a crossover will occur between them. Groups of genes that are linked are called linkage groups.

Simple measurement of linkage

Two-factor crosses involve crossing a double heterozygote to a double recessive. The frequencies of different phenotypes in the progeny equal the frequencies of different gametes in the double heterozygote. The proportion of recombinant gametes is the recombination frequency. This is used to give a measure of the distance between two genes. The percentage recombination between two genes is taken as the distance they are apart. One percent recombination equals one map unit or centimorgan (cM). In linkage analysis in humans it is more common to utilize molecular techniques to analyze genotypes than to study phenotypes.

Three-factor crosses

These are more accurate than two-factor crosses in that they identify and utilize many of the double crossovers that are missed by the two-factor cross. They allow ordering of genes and generate additive map distances.

Interference

It is difficult for chiasmata to form close to one another. For this reason the number of double crossovers observed in three-factor crosses may differ from that predicted from the frequency of single crossovers. If fewer crossovers are observed this is termed positive chromatid interference. This is measured as the coefficient of coincidence.

Linkage analysis in fungi

In ascomycete fungi that have ordered asci, first and second division segregation patterns can be used to determine distance between a gene and the centromere. A similar approach can be used to estimate distances between genes.

Recombination frequency and physical distance

The distance between genes as measured by recombination frequencies is not a precise measure of the physical distance because the frequency of crossing-over varies in different parts of the genome. It is useful for deciding on gene order. Physical maps provide distance between genes in absolute terms.

Related topics

Concepts of genomics

Meiosis and gametogenesis

Genetic diseases