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Transcript
Positional cloning: Getting there by linkage In most instances, human disease genes cannot be localized by physical landmarks, e.g., deletions or translocations Genetic linkage analysis is thus essential and requires: – large number of families – marker polymorphisms in the families – informative meioses HD: Proof of principle and 10 long years The principle was to find a closely linked marker – G8 marker found after only 12 attempts! (1983) – large families were a key resource – mapping to Chrm. 4 by somatic cell hybrids Finally: gene discovery by transcript analysis Confirmation by mutation analysis: a trinucleotide repeat (1993)
