Positional Cloning
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Transcript of Positional Cloning
Positional Cloning
LO
D
Sib pairs Chromosome Region Association Study
Genetics
GenomicsPhysical 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 AssociationAllelic AssociationA Special Type of LinkageA Special Type of Linkage
3/5 2/6
3/2 5/2
3/5 2/6
3/6 5/6
Both families are ‘linked’ with the marker, but a different allele is involved.
This is Linkage but no Association
Allelic AssociationAllelic AssociationA Special Type of LinkageA Special Type of Linkage
3/6 2/4
3/2 6/2
3/5 2/6
3/6 5/6
All families are ‘linked’ with the markerAllele 6 is ‘associated’ with disease
4/6 2/6
6/6 6/6
Linkage is just association within families
Allelic AssociationAllelic AssociationA Special Type of LinkageA Special Type of Linkage
3/6
2/43/2
6/23/5
2/6
3/6 5/6
Allele 6 is ‘associated’ with disease
4/62/6
6/6
6/6
3/4
5/2
Controls Cases
Association study: UsesAssociation study: Uses
Pharmacogeneticsgenotyping clinically relevant samples (toxicity vs efficacy)
Insurance purposescontentious, but likely at some point
Candidate genes for specific diseasescommon practice in medicine/genetics
Positional cloningthe most frequent source of new loci at present
Genome-wide association with 2-3 million SNPs, can search whole genome exhaustively