General Explanation There are 2 input files –The locus file describes the loci being analyzed and parameters for the different analyzing programs. –The pedigree file describes the pedigrees being analyzed. Locus File: The first 3 lines describe some general parameters of the analysis being performed. Following are lines that describe each locus. The end of the file provides recombination information and program- specific information. Pedigree File: Each line in this file describes an individual in one of the pedigrees. In the rest of the presentation:  To see details, clique on highlighted areas.  To return to main page, clique back arrow.

Number of loci Chromosome order of the loci Affection Status locus Numbered Alleles locus Recombination values Parameters for SuperMlink: recombination to be varied, increment, final recombination value Program code: 4=SuperLinkmap 5=SuperMlink No. of Complex Affection loci (0 or 2) Number of alleles for 1 st locus Gene frequencies for 2 nd locus Number of penetrance classes for Affection Status locus Penetrances 0 0 Locus File

Pedigree File Pedigree Number Individual’s ID Father’s ID Mother’s ID First child’s ID Next paternal sibling’s ID Next maternal sibling’s ID Sex: 1=male 2=female Disease Status: 0=unknown 1=unaffected 2=affected Penetrance Class Marker Alleles (2 alleles per locus) st marker 2 nd marker

Locus file (for a sex-linked two-locus disease) << COMPLEX, NO. OF ALLELES << GENE FREQUENCIES 4 2 << COMPLEX, NO. OF ALLELES << GENE FREQUENCIES 2 << NO. OF LIABILITY CLASSES << PENETRANCES 3 4 << ALLELE NUMBERS, NO. OF ALLELES Sex-linked Analysis 2 complex affection loci 1 st complex affection locus 2 nd complex affection locus Penetrances for 1 st penetrance class Female penetrances Male penetrances Penetrances for 2 nd penetrance class Parameters for SuperLinkmap: locus varied, finishing value, number of evaluations. SuperLinkmap program

Pedigree file (for a sex-linked two-locus disease) Phenotype description corresponding to both complex affection loci (includes disease status and penetrance class) Phenotype information

Locus File Number of loci participating in the analysis

Locus File Risk Locus (this parameter is not used by Superlink, see Linkage user manual for a more detailed explanation)Linkage user manual Mutation locus, Mutation male, Mutation female and haplotype frequencies (these parameters are not used by Superlink, see Linkage user manual for a more detailed explanation) Linkage user manual Sex difference, interference (these parameters are not used by Superlink, see Linkage user manual for a more detailed explanation )Linkage user manual

Locus File No. of complex affection loci in the analysis: 0 indicates that the affection status is influenced by one locus (one-locus disease). 2 indicates that the affection status is influenced by two loci (two-loci disease). See Tlinkage manual.Tlinkage manual

Locus File Type of locus: 1 for affection status locus. 3 for numbered alleles locus. 4 for complex affection locus.

Locus File There are 2 possible alleles for the 1 st locus in input order. There are 4 possible alleles for the 2 nd locus in input order.

Locus File The number of penetrance classes for Affection Status locus. Each individual in the pedigree belongs to one of the classes.

Locus File Penetrances. There is a line for each penetrance class with the following probabilities: P(affected | h,h) P(affected | h,d) P(affected | d, d) (the disease locus has 2 alleles: h  healthy, d  disease)

Locus File The recombination values between each 2 consecutive loci on the chromosome. The number of recombination values equals the number of loci in the analysis minus 1.

Locus File The program will calculate the likelihood at the following recombination values: the initial values: 0.1, , , 0.1 SuperMlink program

Pedigree File Father’s ID (0 means founder, an individual with no parents in the pedigree) Mother’s ID (0 means founder, an individual with no parents in the pedigree) First child’s ID (0 means that the individual has no children in the pedigree) Next paternal sibling’s ID (0 means that this individual has no paternal siblings in the pedigree) Next maternal sibling’s ID (0 means that this individual has no paternal siblings in the pedigree)

Pedigree File Proband: (this parameter is not used by Superlink, see Linkage user manual for a more detailed explanation) Linkage user manual

Locus file (for a sex-linked two-locus disease) << COMPLEX, NO. OF ALLELES << GENE FREQUENCIES 4 2 << COMPLEX, NO. OF ALLELES << GENE FREQUENCIES 2 << NO. OF LIABILITY CLASSES << PENETRANCES 3 4 << ALLELE NUMBERS, NO. OF ALLELES Female penetrances: There is an entry for each genotype combination at the 2 loci. Male penetrances: There is an entry for each allele combination at the 2 loci. h | hh | dd | d h | h h | d d | d 1 st Complex Affection locus 2 nd Complex Affection locus hd h d 2 nd Complex Affection locus 1 st Complex Affection locus

Locus file (for a sex-linked two-locus disease) << COMPLEX, NO. OF ALLELES << GENE FREQUENCIES 4 2 << COMPLEX, NO. OF ALLELES << GENE FREQUENCIES 2 << NO. OF LIABILITY CLASSES << PENETRANCES 3 4 << ALLELE NUMBERS, NO. OF ALLELES The program will calculate the likelihood at the following recombination values: the initial values: 0.0, , , , , , 0.0 SuperLinkmap program

Pedigree file (for a sex-linked two-locus disease) Even though there are 3 loci in the analysis, there are only 2 phenotype descriptions. The reason for this is that there is only 1 phenotype description that corresponds to both complex affection loci.