Genetic linkage

Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked. Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked. Genetic linkage is the most prominent exception to Gregor Mendel's Law of Independent Assortment. The first experiment to demonstrate linkage was carried out in 1905. At the time, the reason why certain traits tend to be inherited together was unknown. Later work revealed that genes are physical structures related by physical distance. The typical unit of genetic linkage is the centimorgan (cM). A distance of 1 cM between two markers means that the markers are separated to different chromosomes on average once per 100 meiotic product, thus once per 50 meioses. Gregor Mendel's Law of Independent Assortment states that every trait is inherited independently of every other trait. But shortly after Mendel's work was rediscovered, exceptions to this rule were found. In 1905, the British geneticists William Bateson, Edith Rebecca Saunders and Reginald Punnett cross-bred pea plants in experiments similar to Mendel's. They were interested in trait inheritance in the sweet pea and were studying two genes—the gene for flower colour (P, purple, and p, red) and the gene affecting the shape of pollen grains (L, long, and l, round). They crossed the pure lines PPLL and ppll and then self-crossed the resulting PpLl lines. According to Mendelian genetics, the expected phenotypes would occur in a 9:3:3:1 ratio of PL:Pl:pL:pl. To their surprise, they observed an increased frequency of PL and pl and a decreased frequency of Pl and pL: Their experiment revealed linkage between the P and L alleles and the p and l alleles. The frequency of P occurring together with L and p occurring together with l is greater than that of the recombinant Pl and pL. The recombination frequency is more difficult to compute in an F2 cross than a backcross, but the lack of fit between observed and expected numbers of progeny in the above table indicate it is less than 50%. This indicated that two factors interacted in some way to create this difference by masking the appearance of the other two phenotypes. This led to the conclusion that some traits are related to each other because of their near proximity to each other on a chromosome. This provided the grounds to determine the difference between independent and codependent alleles. The understanding of linkage was expanded by the work of Thomas Hunt Morgan. Morgan's observation that the amount of crossing over between linked genes differs led to the idea that crossover frequency might indicate the distance separating genes on the chromosome. The centimorgan, which expresses the frequency of crossing over, is named in his honour. A linkage map (also known as a genetic map) is a table for a species or experimental population that shows the position of its known genes or genetic markers relative to each other in terms of recombination frequency, rather than a specific physical distance along each chromosome. Linkage maps were first developed by Alfred Sturtevant, a student of Thomas Hunt Morgan. A linkage map is a map based on the frequencies of recombination between markers during crossover of homologous chromosomes. The greater the frequency of recombination (segregation) between two genetic markers, the further apart they are assumed to be. Conversely, the lower the frequency of recombination between the markers, the smaller the physical distance between them. Historically, the markers originally used were detectable phenotypes (enzyme production, eye colour) derived from coding DNA sequences; eventually, confirmed or assumed noncoding DNA sequences such as microsatellites or those generating restriction fragment length polymorphisms (RFLPs) have been used.