Linkage - the tuberous sclerosis gene TSC1 on chromosome...

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Linkage What is it? Mendel's second law (of independent assortment) breaks down in one important way - when two genes lie close together on the same chromosome. In this case, alleles which were inherited from one parent tend to stick together when transmitted to the next generation because they are part of the same DNA molecule. However, the further apart two genes are along the molecule, the more likely it is that a meiotic crossover can occur between them and thus create a new combination of alleles. By measuring the frequency of recombinant chromosomes in the progeny, we can estimate the distance that separates the two genes and can make a genetic map . Such maps are not made just to satisfy scientific curiosity, they have direct application both in science and in medicine. First, by mapping the gene responsible for a genetic disease, we can identify it even when we have little or no idea what it does. For examples, see the cystic fibrosis cloning story or the cloning of TSC1 (M. van Slegtenhorst et al.Identification of
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Unformatted text preview: the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277:805-808, 1997.) . • Also, even before a gene is identified, if it can be mapped with respect to other genes or to anonymous segments of DNA (known as markers or marker loci ), then information gained from studying the linked loci can be used to deduce, for instance, whether or not a person is a carrier of a mutant gene or to give antenatal diagnosis as to whether an embryo is affected with the disease. The mathematics of linkage analysis can be frightening. However, the fundamentals of the subject are easy to grasp particularly if we start by studying experimental organisms in which we can set up those crosses which we need. Later on we must consider how to make the same type of measurements in humans whose "crosses" cannot be experimentally manipulated but where we must make deductions from families in which genetic diseases (or interesting variants) are present....
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This note was uploaded on 11/22/2011 for the course CHEMISTRY CHM1025 taught by Professor Laurachoudry during the Fall '10 term at Broward College.

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