8.2 Genetic model

In earlier versions of MORGAN there were three genetic data types. Data could be genotypic, typically used for marker data, discrete, a data type for binary data requiring specification of incomplete penetrances, or quantitative, using a Gaussian penetrance with specification of genotypic means and residual variance.

As yet, loci are either multiallelic marker loci assumed observed without error, or trait loci which may have general penetrance functions but are diallelic. Gradually, available models are being generalized:

1. Pedigree peeling for multiallelic loci with general penetrance;

   In order to allow models for "non-genotypic" markers, general joint peeling programs have been implemented, based on Thompson (1976: University of Utah, Bioinformatics Tech Rept, #6). For zero-loop pedigrees, these peeling routines are used by the lm_map program which allows for errors in marker data. For general pedigrees, they are not yet released, as they are still in process of testing.

2. Penetrance functions and trait models:

   From MORGAN V2.8.2, liability classes (previously available only for lm_bayes) have been implemented for the discrete-trait penetrance model in lm_markers and lm_multiple. Penetrances for each liability class are now read from an input file using the "input extra data file S" parameter statement.

   Additionally, an age-based penetrance function for a qualititative trait has been implemented. That is, penetrances are directly dependent on age, rather than going through a liability class specification.

3. Traits and trait loci:

   The new program lm_twoqtl allows two (linked or unlinked) quantitative trait loci to contribute additively or epistatistically to a single trait (see Sung et al., 2007, Genetic Epidemiology 31: 103-114). A polygenic component may also be also be included. In two-locus penetrances may be specified as additive, with a genotypic mean for each trait genotype for each locus. Alternatively, a matrix array of 2-locus genotypic means may be specified, allowing for epistasis (see Sung & Wijsman, 2007, Human Heredity 63: 144-152.).

   With more these more complex trait models, including those of lm_twoqtl (see Sung et al., 2007, Genetic Epidemiology 31: 103-114), a more general specification of traits is required. In MORGAN V3.0, completely new structures have been introduced, separating traits (phenotypes) from trait loci ("tlocs"). Traits may be affected by genotypes at several tlocs; the genotypes at a tloc may affect several traits.