EASYPAT 29.08.2000 EASYPAT is a computer program that allows calculation of likelihood ratios for single locus data, comparing specific types of simple hypotheses regarding the familial relationships involved. Currently, these hypotheses include 1. Parenthood vs. non-Parenthood in duos comprising parent and child (DIRECT=2). The program also calculates the likelihood under the hypothesis that, instead of the putative parent, a first degree relative is the biological parent. 2. Paternity vs. non-paternity in trios comprising mother, child and alleged father (DIRECT=3). The likelihood is also given under the hypothesis that a first degree relative of the alleged father is the biological father. 3. Full sibs vs. halfsibs in trios comprising one parent and two children (DIRECT=4). In this case, the likelihood is also calculated assuming that the unknown parents are first degree relatives. EASYPAT requests an input file of the following format: 1. line; DIRECT, a single positive integer that identifies the types of hypotheses compared (see above). 2. line; NMARK, a single positive integer indicating the total number of markers tested. All individuals must be typed for all markers included. Following lines; for each marker, enter the name of the marker and the genotypes of the respective individuals in the order: DIRECT=2 - child, putative parent DIRECT=3 - mother, child, putative father DIRECT=4 - parent, 1. child, 2. child All entries must be separated by at least one blank. Therefore, blanks must not be part of marker or allele designations! 3 5 THO1 199 199 196 199 192 196 D19 210 234 230 234 230 234 CSF 311 315 311 311 311 315 VWA 152 156 152 160 140 160 CYAR 177 177 177 196 196 196 In this example, mother, child and putative father have been typed at five markers. The allele frequencies and mutation rates necessary to calculate likelihoods are enquired by the program during execution. Entering the following allele frequencies for the above example THO1 196 : 0.30 D19 230 : 0.20 CSF 311 : 0.15 VWA 160 : 0.15 CYAR 196 : 0.25 yields the following output Paternity vs. Non-paternity Likelihood ratio : 1.9841269841E+02 W value : 99.49853% First degree relative Likelihood ratio : 2.8888888889E+01 W value : 96.65428% apriori posteriori [1.degree relative] ----------------------------------------- 0.1 95.66082% 76.24633% 0.2 98.02384% 87.83784% 0.3 98.83767% 92.52669% 0.4 99.24967% 95.06399% 0.5 99.49853% 96.65428% 0.6 99.66513% 97.74436% 0.7 99.78447% 98.53817% 0.8 99.87416% 99.14204% 0.9 99.94403% 99.61686% ----------------------------------------- Alternatively, allele frequencies can be loaded from an input file of the following format 1. line; SNMARK, a single positive integer equal to the number of markers for which allele frequencies are to be stored. The following will be repeat SNMARK times 2. line; marker designation and number of alleles (NALL), separated by at least one blank. The marker designation must start at the first position of this line. Do not include leading blanks. NALL lines; allele designation and allele frequency, separated by at least one blank. The allele designation must start at the first position of this line. Do not include leading blanks. 3 D2S367 4 141 0.40134 139 0.33779 115 0.23311 143 0.02776 D12S66 3 167 0.37841 171 0.26809 163 0.35350 D8S601 5 228 0.37703 224 0.21486 226 0.16689 230 0.13446 222 0.10676 Please note that marker and allele designations in the two types of input file must be IDENTICAL, otherwise the program will not be able to identify alleles properly. Frequencies of unidentifiable alleles will be enquired during program execution. Computational methodology employed in EASYPAT - Trios (DIRECT=3) The likelihood of paternity, L1, is calculated by considering the four possible inheritance patterns of the parents. L1 is increased by 1/4 for each pattern that is compatible with the offspring genotype. The likelihood of non-paternity, L2, is calculated considering only the two possible inheritance patterns of the mother. If a pattern is compatible with the offspring genotype, this defines a paternal allele, say A, and L2 is increased by half the population frequency, f(A)/2, of this allele. If the paternal genotype is not compatible with the offspring genotype, i.e. if the putative father does not carry any of the necessarily paternal alleles, then L1 is set equal to the overall mutation rate and L2 is set equal to either 1-f(A), if the genotype of the putative father is AA, or 1-f(A)-f(B), if the genotype of the putative father is AB. The information used in this instance is thus confined to the fact that the paternal allele of the child is different from the allele(s) carried by the putative father. Implicitly, it is also assumed that each allele is equally likely to mutate. If the maternal genotype is not compatible with the offspring genotype, the program is aborted. The likelihood, L3, of a first degree relative of the putative father being the biological father is calculated as (L1+L2)/2. (Half of the genetic material of the two is identical, the other half is unrelated). - Duos (DIRECT=2) The likelihood of parenthood, L1, is the same as L2 is for trios. The likelihood of non-paternity, L2, equals the population frequency of the offspring genotype under Hardy-Weinberg conditions. If the parental genotype is not compatible with the offspring genotype, L1 is set equal to the overall mutation rate while L2 is set equal to 1-f(A), if the putative parent is AA, or 1-f(A)-f(B), if the putative parent is AB (see above). The likelihood L3 of parenthood by a 1. degree relative is again calculated as (L1+L2)/2. - Trios (DIRECT=4) The likelihoods of full sibship, L1, and half-sibship, L2, are calculated considering the four possible segregation patterns of the typed parent. If a pattern is compatible with the two offspring genotypes, this defines alleles A and B that must have been inherited from the untyped parent(s). If A is not equal to B then L2 is increased by f(A)*f(B)/4, and L1 is increased by f(A)*f(B)/8. If A=B, then L2 is increased by f(A)*f(A)/4 and L1 is increased by f(A)*[1+f(A)]/8. The likelihood L3 in this case refers to the hypothesis that the untyped parents of the two offspring were 1. degree relatives. Best wishes MK