From QTL to QTG: Are we getting closer? Sagiv Shifman and Ariel Darvasi. The Hebrew University of Jerusalem. Presentation Outline. Overview of fine QTL mapping strategies Inbred strain sequence/haplotype information for fine QTL mapping
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The Hebrew University of Jerusalem
Advanced intercross lines (AIL)
CI = CIF2 / (t/2)
HDL – QTL
Wang et al. 2003
Eight-way cross of:
C57BL/6, BALB/C, RIII, AKR, DBA/2, I, A/J C3H
Established 30 years ago (~60 generations)
McClearn et al.
Open field activity
Talbot et al. 1999
0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
Paigen et al.
Males, recombinant at an interval of interest, are progeny
tested to check which QTL allele was retained.
ISCS are produced by a series of backcrosses and intercrosses
Grupe et al. 2001
Chesler et al. 2001
Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse
Wiltshire et al. 2003
Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice
Yalcin et al. 2004
Multiple Cross and Inbred Strain Haplotype Mapping of Complex-Trait Candidate Genes
Park et al. 2003
QTL detection with two inbred lines (P1 and P2)
Estimating QTL map location
Sequence based fine mapping
Selecting an optimal new inbred strain (Pi)
2 strains Strain Haplotype Mapping
4 strainsMapping Resolution: Chromosome 16
Low resolution region Strain Haplotype Mapping
High resolution region
Until we have the 1K RI set any QTL mapping strategy is like riding a bike: it’s fun and we can get very far –
Once we get something with an engine though, we will feel the difference!
… we are still missing an engine for the “end-game” – Genetics is not everything