Transcript No Slide Title

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)