Download Slide 1

Positional Cloning
Genetics
Sib pairs
Chromosome Region
Association Study
Genomics
Physical Mapping/
Sequencing
Candidate Gene Selection/
Polymorphism Detection
Mutation Characterization/
Functional Annotation
Netherton Syndrome Linkage
Chavanas et al., Am J Hum Genet, 66:914-921, 2000
Netherton Syndrome Haplotypes
Chavanas et al., Am J Hum Genet,
66:914-921, 2000
Chavanas et al. 2000, Nature Genetics
Inflammatory Bowel Disease Genome Screen
Hampe et al., Am J Hum Genet, 64:808-816, 1999
Inflammatory Bowel Disease Genome Screen
Hampe et al., Am J Hum Genet, 64:808-816, 1999
Allelic Association
A Special Type of Linkage
3/5
3/6
2/6
5/6
3/5
3/2
2/6
5/2
Both families are ‘linked’ with the marker, but a different
allele is involved.
This is Linkage but no Association
Allelic Association
A Special Type of Linkage
3/5
3/6
2/6
5/6
3/6
3/2
2/4
6/2
4/6
6/6
All families are ‘linked’ with the marker
Allele 6 is ‘associated’ with disease
Linkage is just association within families
2/6
6/6
Allelic Association
A Special Type of Linkage
Controls
Cases
6/6
6/2
3/5
3/4
3/6
2/4
3/2
5/6
3/6
4/6
6/6
2/6
5/2
Allele 6 is ‘associated’ with disease
2/6
Association study: Uses
Pharmacogenetics
genotyping clinically relevant samples (toxicity vs efficacy)
Insurance purposes
contentious, but likely at some point
Candidate genes for specific diseases
common practice in medicine/genetics
Positional cloning
the most frequent source of new loci at present
Genome-wide association
with 2-3 million SNPs, can search whole genome exhaustively