23 Positional Cloning and Linkage Analysis
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Strategy of mapping a gene by linkage analysis
The strategy of mapping a disease gene by linkage analysis is described in
Figure 4. The first requirement is genomic DNA from families affected with
the disease. The second requirement is a set of polymorphic DNA markers,
which are relatively evenly distributed over the human chromosomes and
for which the localization is well known.
In the example given a microsatellite marker (see Figure 3) that localizes
to chromosome lp13.3 has been typed in a family with an autosomal recessive disease, the localization of which is indicated by an "X" on chromosome 1. The father has the alleles 100 bp and 98 bp, while the the mother has
the alleles 96 bp and 94 bp.
Fig. 4. Strategy of
mapping a disease gene
by linkage analysis
(see text).
I. Genomic DNA of Affected Families
D-r ii06
100 bp
98 bp
96 bp
94 bp
--II. Hiqhly Polymorphie DNA Markers
Chromosome
1
2
3
22
~
t
# .... ••
DNA Marker (e.g., 1 p13.3)