4 - Biol 241 2010 Lecture 7&8 Linkage analysis I Gene...

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Biol 241 - 2010 I) Gene mapping based on coinheritance, “linkage” A) Mendelian principle of independent assortment has to be modified for linkage Independent assortment still holds so long as the genes are located on different chromosomes or if they’re far enough apart on the same chromosome. Bateson and Punnett first demonstrated linkage between two genes. They conducted classical Mendelian experiments that showed that intercrossing F1 organisms heterozygous for two characteristics each with a simple dominance/recessivity relationship did not assort in the familiar 9:3:3:1 ratio (coupling). A higher frequency of F 2 plants of the same phenotype as the parental strains. The parental combination of alleles stayed together into the F 2 generation. Morgan observed a similar result with Drosophila . He suggested that the two genes were located on the same homologous chromosomes and the recombinants were generated by crossovers during meiosis. The result of having the two genes on the same chromosome and located closely together so that they’re not often separated by recombination. Some recombination still does happen. So there are actually four types of gametes. The majority of the gametes represent the same combination of alleles found in the parents (parental gametes). A minority of the gametes represent two new combination of alleles (the recombinant gametes). B) Measuring recombination frequency directly. These Mendel-like experiments could be used to determine how close two genes are based on how many recombinants occur in the F2, it is cumbersome. More useful is the testcross in which the genotype of the recombinant is revealed directly by placing the recombinant chromosome opposite a chromosome with recessive alleles. The recessive alleles on this chromosome allow whatever alleles are on the recombinant chromosome to be revealed. The percentage of recombinants (the “ recombination frequency ”) can then be determined directly from the phenotype of the resulting organisms. II) Alfred Sturtevant: employing recombination frequencies for full scale mapping of multiple genes along a chromosome. A) The mapping of a chromosome was done first with the X chromosome of Drosophila. 1
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Biol 241 - 2010 B) Test crosses can then be conducted to determine their relative position. Two gene (two point) testcrosses allow the distance between two genes to be measured. The distance is equal to the frequency of recombination times 100. The units are called map units or centiMorgans (cM) . In humans a cM is about 1 million base pairs.
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4 - Biol 241 2010 Lecture 7&8 Linkage analysis I Gene...

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