A. Novelletto, F. De Rango
Dept. Cell Biology, University of Calabria GENOTYPING
CONCORDANT / DISCORDANT COUSIN PAIRS
A. Novelletto, F. De Rango
Dept. Cell Biology, University of Calabria GENOTYPING
CONCORDANT / DISCORDANT COUSIN PAIRS
SUMMARY OF STUDY DESIGN CONCORDANT DISCORDANT IBD 25% 25% IBD > 25% < 25% Parametric Non parametric I-1 I-1
QUESTIONS RAISED IBD ≠ IBS ; to what extent this difference affects the feasibility
Power of the experiment
How can info on the age of I-2, II-1 and II-2 be exploited
Under which circumstances the typing of I-1 becomes informative
Can the linkage analysis be extended to physical variables (e.g. MMSE, handgrip)
Response to selection design Marker gene diversity n. of pairs n. of typings for centenarians Param. vs. non param. analysis RELEVANT VARIABLES
EXPLORING THE PERFORMANCE OF THE DESIGN DATA SIMULATION
EVALUATION WITH AVAILABLE SOFTWARE Parametric LOD score NPL score QTL mapping concordant disc.
ftp://ftp-genome.wi.mit.edu/distribution/software/genehunter Very rapid extraction of complete multipoint inheritance information from pedigrees of moderate size.
This information is then used in exact computation of multipoint LOD scores, non-parametric linkage statistics, and now in a wide range of sibpair analyses and a new variance components analysis.
The multipoint inheritance information allows the reconstruction of maximum-likelihood haplotypes for all individuals in the pedigree and information content mapping which measures the fraction of the total inheritance information extracted from the marker data. GENEHUNTER
PART 1 - effect of: n. of pairs
marker allele freq.
CONCORDANT – all pairs alike 1/2 1/2 1/2 2/3 1/2 3/4 2 sharing 1 sharing 0 sharing I-1
CONCORDANT, common marker allele (q = .20),
recessive model LOD score 0 sharing 1& 2 sharing n. of pairs -1.00E-02 -6.00E-03 -2.00E-03 2.00E-03 6.00E-03 1.00E-02 1 24 48
CONCLUSION SET 1 - CONCORDANT NPL more appropriate
Dramatic effect of allele frequencies at marker loci
Minor advantage in typing I-1 in CONCORDANT pairs
PART 2 - effect of response to selection design
CONCORDANT – different proportions of 0, 1, 2 sharing 1/2 1/2 1/2 2/3 1/2 3/4 2 sharing 1 sharing 0 sharing I-1
CONCLUSION SET 2 - CONCORDANT
Dramatic effect of allele frequencies at marker loci confirmed
Haplotyping (and perhaps search for private SNPs) needed to increase marker diversity
Ratio of non sharing/sharing cousin pairs approaching 1:1 preferred
Entire study needed to reach significance with concordant pairs only
PART 3 - effect of: n. of pairs
marker allele freq.
DISCORDANT – all pairs alike 1/2 1/2 1/2 2/3 1/2 3/4 2 sharing 1 sharing 0 sharing Very different liabilities for genotypes at the “longevity” locus I-1
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