ASP 26.07.2001

The program ASP is a versatile power calculator for gene mapping,
using a sibpair design (concordant or discordant). It employs a 
diallelic model for the trait locus. Based upon the population 
frequency of the disease allele (or allelic class) and the 
genotype-specific penetrances, ASP simulates the parental and 
offspring trait locus genotypes assuming Hardy-Weinberg equilibrium 
for the parental generation. Marker locus genotypes are simulated 
conditional upon the inheritance pattern at the trait locus, 
allowing for recombination. The marker genotypes are tested for 
non-Mendelian ibd sharing using an unrestricted likelihood ratio 
test. The power of the dataset is also determined using a likelihood 
ratio test that restricts maximization to z(1)^2=4z(0)z(2) and 
z(0)<=1/4, in the case of affected sibpairs, or z(2)<=1/4 for 
discordant sibpairs,respectively (here, z(i) denotes the probability 
of the sibs sharing i alleles ibd).

The input file contains the simulation parameters in fixed 
order. All figures must be separated by at least on blank, 
but can be spread over any number of lines.

NSIM (the number of simulations for power calculation;
      it is recommended to choose NSIM>=1000 )
CONC (1=affected sibpairs, 0=discordant sibpairs)
NSIB0 NSIB1 NSIB2 (number of sibpairs with 0, 1 or 2 parents typed)
FREQ (population frequency of the mutant trait locus allele, 0<FREQ<1)
PENE0 PENE1 PENE2 (penetrance of genotype with 0, 1, or 2 copies
                   of the mutant trait locus allele, 
                   0<=PENEi<=1, 0<PENEi for at least one i)
RECF (recombination fraction between disease and marker locus, 0<=RECF<=0.5)
NALL (number of alleles at marker locus, 0<NALL<=20)
ALF1 ALF2 etc. (allele frequencies at marker locus, 0<ALFi<1)

Here is an example:

1000
1
220 60 20
0.10
0.05 0.10 0.50
0.05
4
0.1 0.2 0.3 0.4

ASP calculates the expected ibd sharing at the trait locus,
the average observed ibd sharing at the marker locus, and 
the power of a likelihood ratio test to detect any deviation
of the latter from Mendelian expectation.

The program runs in DOS mode; the names of the input and 
output files can be entered at runtime or may be included 
in the command line.

c:>asp

or

c:>asp inname outname

where inname and outname can be any valid DOS file names.

Simulation may take a while. The program ASPSHARE complements 
ASP in that it allows rapid calculation of the expected ibd 
sharing at the trait locus, based upon the mutation frequency 
and penetrances. ASPSHARE asks for these parameters at runtime 
and does not require any input file. The program also provides 
the prevalence emerging for the respective parameters. 

Best wishes
MK