The identification of - and D9S150 because individuals were...

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The identification of 'positional candidate' genes The identification of a disease gene proceeds by about 5 steps. First families are "collected" and the clinical investigation is repeated to ensure that there are no misdiagnoses of unaffected individuals, DNA samples are prepared (usually from a 10ml blood specimen). When there are enough families to give a chance of a significant positive Lod score, the DNA is amplified by PCR from about 200 polymorphic marker loci spread throughout the genome. That should ensure that one locus is within about 7.5 cM of the disease gene. When that initial linkage is found, many more loci from the same region are also tested in the families and recombinants are used to define the genetic interval within which the disease gene must lie. In the TSC1 example above, the gene was initially defined as being between D9S149 and D9S114 . Later this interval was reduced to between D9S2127
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Unformatted text preview: and D9S150 because individuals were found who had inherited only part of the chromosome due to genetic recombination in the formation of the gamete from their affected parent. • Most areas of the human genome have now been cloned. Clones covering the minimum area are identified and used to find all the genes in the area. • Mutations in these genes are sought in the affected patients. Hopefully this should lead to that "Eureka" moment. • As more and more of the genome is sequenced already, several of these steps may be bypassed. It may be possible to jump directly from the definition of the genetic interval within which the gene must lie to the mutation screen. As well as the TSC1 success story above there have been many other examples of successful identification of disease genes based solely, or almost solely, on positional information. The classic example is the cystic fibrosis gene CFTR ....
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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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