Current and future MORGAN developments: August 2007.
Updated March and August 2008, March 2009

A preliminary version of MORGAN-3, containing only the PedComp, Genedrop, and Autozyg programs, was released in March 2008. The full version of the package (including two new programs) is released March 2009, although it remains a beta-test version with much testing and documentation remaining to be done.

The current MORGAN Tutorial and Examples released in August 2007 are based on MORGAN 2.8.1. We therefore here detail developments of MORGAN 2.8.2 and MORGAN 2.8.3, as well as upcoming changes, and the development of MORGAN 3.0. The information is taken from the Future directions section of the 2007 MORGAN Tutorial. The information remains pertinent to MORGAN 2.9.

1. General Library functions:

• 1. Hidden Markov computations:
  In MORGAN V2.8.2, forward HMM computation for multiple meioses has been replaced by a factored version (FHMM), enabling much faster exact computation on small pedigree components and multiple-meiosis sampling for larger numbers of meioses.
  Exact computation of lodscores on small pedigree components has been implemented for `lm_markers': computation uses the FHMM version of the Baum algorithm.
  
• 2. Multiple meiosis sampler:
  MM-sampler updates multiple meioses jointly and is therefore a generalization of the meiosis sampler (M-sampler). There are four types of update in MM-sampler: random meiosis update, individual update, sib update and 3-generation update. This is based on work by Liping Tong.
  For more detail on L- and M-samplers, see the tutorial section in ``Using MCMC to Estimate Parameters of Interest in Pedigree Data.''
  
• 3. MCMC and pedigree peeling by component
  Up to MORGAN V2.8.2, MCMC was performed globally over pedigree components (except those small enough for exact computation). The L-sampler peeling and lod score estimation could be done either by component (using "set peeling by component") or globally (the default).
  With MORGAN V2.8.3, and specifically to accommodate the new `lm_haplotype' program, the preferred option is to do both MCMC and pedigree peeling (lod score estimation) by component, and to use exact computation on all sufficiently small component pedigrees. The alternative, retained so that older data sets can be rerun, is to use "set global MCMC", in which case no exact computation will be done, and MCMC will be done globally over all component pedigrees. In this case, the "set peeling by component" option is retained.
• 4. Pedigree peeling for multiallelic loci with general penetrance;
  As yet, loci are either multiallelic marker loci assumed observed without error, or trait loci which may have general penetrance functions but are diallelic. In order to allow models for "non-genotypic" markers, general joint peeling programs have been implemented, based on Thompson (1976: UU Tech Rept, #6). These peeling routines are used by the `lm_map' program which allows for errors in marker data. They are not yet released, as they are still in process of testing: they are not yet released in MORGAN V2.8.3.
  
• 5. Penetrance functions and trait models:
  In MORGAN V2.8.2, liability penetrances (previously available only for `lm_bayes') have been implemented for `lm_markers'. 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.
  In two-locus models for a quantitative trait, 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 and Wijsman, 2007, Human Heredity 63: 144-152).
• 6. Traits and trait loci:
  With 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. This more general structure is not yet released - see `lm_twoqtl' below.

2. Autozyg programs:

• 1. Map estimation: `lm_map' with and without error models:
  Some updates and corrections to the `lm_map' program are made in MORGAN V2.8.2. Additonally under development is a version of `lm_map' which allows for error in observation of marker genotypes. This version may be released with MORGAN V2.8.3.
• 2. Latent p-values: (including programs using Lodscore statistics)
  The version of the program `lm_pval' released in MORGAN V.2.8 and subsequent, and described in this tutorial, uses the latent p-value distribution of Thompson and Geyer (2007, Biometrika). Additional programs using these ideas are under development, including programs for the distribution of latent lod scores obtained in MCMC sampling (`lm_fuzlod'), p-values and randomized tests based on latent lod score statistics (`lm_fzplod'), and randomized confidence sets for the location of a trait locus (`lm_fzconf'). These are working names only. The methods are described in Thompson (2007: submitted).
  
• 3. Gold (Gold2) and Gold1 subdirectories:
  In MORGAN V2.8.3, `Gold' replaces the previous `Gold2' subdirectory, for tests of `lm_auto', `lm_pval', `lm_map' and `lm_ibdtests'.
  Gold1 `lm_auto' tests remain temporarily, since they provides the only tests of MCMC samplers on looped pedigrees. Gold1 `lm_auto' gold standards were omitted from the released MORGAN V2.8.2, due to delays in checking looped pedigree peeling routines: they will be reinstated in MORGAN V2.8.3.

3. LR_Lods programs:

The Gold1 subdirectory remains temporarily, since it provides the only tests of MCMC samplers on looped pedigrees. Gold1 `lm_lods' gold standards were omitted from the released MORGAN V2.8.2, due to delays in checking looped pedigree peeling routines: they will be reinstated in MORGAN V2.8.3.

4. Lodscore programs:

• 1. `lm_multiple' and `lm_markers'
  A new lod score calculation program `lm_multiple' was released in MORGAN V2.8.2 (Spring, 2006). The `lm_markers' program is still made as a separate executable, but is compiled as a special case of `lm_multiple' code. In V2.8.2, both programs perform exact lodscore computations on small pedigree components. In V2.8.3 (unreleased) this is optional: see `lm_haplotype' below.
  The difference between `lm_multiple' and `lm_markers' is that the new `lm_multiple' substitutes the old single-meoisis M-sampler updates for the new multiple-meiosis (MM) sampler that is the work of Liping Tong (Tong & Thompson, 2007, Human Heredity:in press): see above.
  `lm_multiple' runs with the same parameter file and other input files required by `lm_markers'. The output is also essentially the same as that from `lm_markers'.
  More information on lod score calculation programs in MORGAN V.2.8.1 (and previous) can be found in the MORGAN Tutorial.
• 2. lm_twoqtl
  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). Full implementation of lm_twoqtl requires the new MORGAN 3.0 structure. However, due to delays in the finalization of MORGAN 3.0, a beta-test version of lm_twoqtl was released under MORGAN 2.8.3.
• 3. `lm_haplotype'
  The `lm_haplotype' program is a generalization of `lm_multiple' in which haplotypes of key individuals dividing the pedigree are sampled in addition to meiosis indicators. To facilitate efficient implementation of this algorithm, new peeling-by-component routines need to be implemented and checked. This program is the work of Liping Tong (Tong and Thompson, 2007, Human Heredity:in press). The program is in process of release: not yet released in MORGAN V2.8.3.
  
• 4. Gold subdirectory (previously Gold1 and Gold2)
  In MORGAN V2.8.2, Gold standards for exact computation and for `lm_multiple' are added in the Lodscore/Gold2 subdirectory.
  In MORGAN V2.8.3, the `Gold' directory replaces the previous `Gold2' directory. Gold directories for `lm_lods' and `lm_schnell' are moved to the new `LR_Lods' program directory. Thus Gold1 no longer exists in Lodscore.

5. MORGAN 3.0 (release-2; March 2009) and two new programs

Additionally there are two new programs:
1) The Autozyg program "gl_auto" is a more general version of the original lm_auto MORGAN program (which is still included in the package). The gl_auto program provides full lm_auto capabilities with the componentwise multiple-meiosis sampling of the lm_multiple program. Additionally it permits output of joint realizations of meiosis indicators or founder genome labels (hence "gl") sampled conditionally on marker data. These realizations may be used in subsequent analyses of trait data using a variety of trait models (e.g.)
2) The PedComp program "translink" also takes lm_auto style input but performs no genetic analyses. This program produces a pedigree file pedfile.dat and output file datafile.dat in LINKAGE format, in accordance with the pedigree, trait, marker, maps and models specified in the MORGAN parameter file, in order that other software can be more easily run using the same or eqivalent input information.