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The power of gene expression profiling to unravel behaviour. Cathy Fernandes, Jose Paya-Cano, Frans Sluyter, Ursula D'Souza, Robert Plomin, Leonard C Schalkwyk. Social, Genetic and Developmental Psychiatry Centre Institute of Psychiatry King ’ s College London. Outline. Background.
Cathy Fernandes, Jose Paya-Cano, Frans Sluyter, Ursula D'Souza, Robert Plomin,
Leonard C Schalkwyk
Social, Genetic and Developmental Psychiatry Centre
Institute of Psychiatry
King’s College London
nominate new candidate genes for behaviour
A/J* BALB/cByJ C3H/HeJ DBA/2J* 129S1/SvImJ*
* Celera Mouse Genome Sequencing Projects
# Public Mouse Genome Sequencing Projects
3. Hierarchical clustering (Eisen, 1998) was carried on the
ANOVA filtered (p < 4 x 10-6) gene expression levels
- the bulk of the probesets expression profiles are very similar
(pairwise correlations between chips MAS5: 0.894 - 0.997, dChip: 0.901 - 0.997)
- numerous and clear strain differences in gene expression
- strains cluster together
(in 10 different random permutation runs of the strain factor to assess the false
positive rate, only two p-values < 4 x 10-6 were found (i.e. 1000 fold fewer than
with the real factor)
- Gas5 gene is known to harbour mutations that affect the
stability of its mRNA transcript in the 129 substrains
(Muller et al 1998)
- Camk2a is implicated in the establishment of long-term potentiation
(Bejar et al 2002) and spatial learning (Silva et al 1992, Giese et al 1998)
- BUT does not correlate with learning in these strains ?
FVB/NJ> SJL/J> BALB/cByJ> C3H/HeJ> DBA/2J> C57BL/6J> 129S1/SvImJ> A/J
- biased towards detection of abundantly expressed, well-
- rare transcripts, short half-life, alternative splicing
BUT low-abundance mRNAs or those expressed only at very specific times in development and/or processes may be key to determining the behavioural phenotype
HS progenitor strains
Wagner parsimony analysis using MIX (Felsenstein 1988b) of microsatellite data (298 loci from all 19 autosomes and X) on 48 strains, transformed into binary characters according to Schalkwyk et al 1999, and using SPRET as outgroup. Internal figures are the number of bootstrap replicates out of 100 supporting each group. The overall topology agrees with Schalkwyk (1999) except that the C57 and 129 groups are reversed.