HAPMAX 05.10.94 The program HAPMAX allows to calculate maximum likelihood estimates of haplotype frequencies. Originally, it has been designed for the analysis of markers associated with recessive disorders (such as CF), and the layout still reflects this initial purpose. The input format for the data file is as follows. 1. line: Number of markers (TNMARK) included in the file. If the sign of this integer constant is positive, the program will read 3 lines per family (1. line: father, 2. line: mother, 3. line: affected offspring). If the sign is negative, only one line per family is expected (i.e. a single individual). 2. - (TNMARK+1). line: Names of the markers included (TNMARK+2). line and following: Genotype data (see above). One line is expected per individual. Each of these lines must include 2*TNMARK positive integer values, denoting the genotypes of the individual at the TNMARK loci, all numbers separated by an arbitrary number of spaces. Enter '0 0' for undetermined genotypes. Last Line: A negative integer indicating end of file. The following is a short example 3 MetH XV2c KM19 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 2 1 1 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 2 2 1 2 1 2 -1 which is equivalent to -3 MetH XV2c KM19 1 1 1 2 1 1 1 2 1 1 1 1 2 2 1 2 1 2 -1 Please note that the program's options to estimate haplotype frequencies on normal chromosomes and/or to control estimates for parental sex are only meaningful for fully typed nuclear families. In such cases, the paternal genotype should occupy the 1., and the maternal genotype should occupy the 2. line in each family. The option to ignore the transmission status of a chromosome will result in haplotype estimation being performed for transmitted and non-transmitted chromosomes combined. This option is critical for obtaining a likelihood ratio statistic to test for equal haplotype frequencies on transmitted and non-transmitted chromosomes. Twice the standard deviation of the haplotype frequency estimate will be determined for the 7 most frequent haplotypes. Under the assumption that the estimates approximately follow a Gaussian distribution, these figures demarcate 95 percent confidence limits for the estimates. HAPMAX can also be executed in batch mode. To this end, all necessary parameters have to be included in the command line, seperated by at least one blank. The order in which the program expects the respective items is as follows: (1) name of the input file (2) number of markers selected for analysis = NMARK (3 to 2+NMARK) numbers identifying individual markers selected (3+NMARK) number of markers selected for exclusion = NMARK2 (4+NMARK to 3+NMARK+NMARK2) numbers identifying individual markers selected for exclusion Note: any data with missing genotypes for at least one of the markers included in this negative list will be ignored, irrespective of whether that marker has been chosen for analysis. if the input file contains trios, the next position is occupied by variable NORMALS NORMALS=0 non-transmitted chromosomes not included NORMALS=1 non-transmitted chromosomes included if NORMALS=1, the next position is occupied by variable IGNORE IGNORE=0 transmission status of chromosomes not ignored IGNORE=1 transmission status of chromosomes ignored if the input file contains trios, the next position is occupied by variable SEPSEX SEPSEX=0 analysis not controlled for parental sex SEPSEX=1 analysis controlled for parental sex the last item is the name of the output file Examples hapmax data1.dat 2 1 7 1 5 1 0 1 data1.res input is from file data1.dat, which contains trio genotypes for at least seven markers; two markers are chosen for analysis, namely nos. 1 and 7; one marker is included in the negative list, namely no. 5; non-transmitted chromosomes are included in the analysis and the transmission status of chromosomes is considered; the analysis controls for parental sex and output is sent to file data1.res hapmax data2.dat 2 3 4 0 data2.res input is from file data2.dat, which contains singleton genotypes for at least four markers; markers nos. 3 and 4 are selected, the negative list is empty; output is sent to file data2.res Best wishes MK