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Cyrillic 2 contains a 'risk locus' disease type that allows the calculation of risks for familial cancers and other complex diseases. As an example of this facility, the Cyrillic program comes pre-loaded with the Claus data set and allows you to calculate familial risks for breast cancer. In order to run the Breast Cancer Susceptibility model, you have a choice of two options:

	Download** a version of FASTLINK (a faster version of the original LINKAGE software) from our web site which has been compiled especially for use with Cyrillic's BrCa model and is available by kind permission of the developers. This version has the maximum number of liability classes set to 60 (well above the 25 required by the BrCa model) and has LOOPSPEED set to 1 (see below for an explanation of the significance of this). With this compilation, you will need to modify the disease settings in Cyrillic for the "BrCa - Breast Cancer Susceptibility" disease definition (see below).

	(** Windows 3.1 users should download the 16 Bit version instead. See the Cyrillic 2 Support page for further details)

	Download an uncompiled version of the LINKAGE software from the Rockefeller or Rice University site and follow the instructions below to compile the software. Further details about these packages is given in the Cyrillic 2.1 Popular FAQ on LINKAGE analysis. Please note, that these need to be compiled to support at least 25 liability classes, and this is not true of earlier pre-compiled versions.
	Important -- Changes to the BrCa disease settings
	The disease settings for "BrCa - Breast Cancer Susceptibility" that shipped with an early version of Cyrillic 2.1 are slightly in error, and will prevent the versions of FASTLINK available from our web site from running. These can easily be changed in a one-time operation: With Cyrillic running in BrCa mode (choose the Breast Cancer Example program icon when starting Cyrillic), click to Select "Data\|Diseases..." and then Select BrCa - Breast Cancer Susceptibility. Click on the Edit button and set the Male and Female Mutation Rates to zero.

	To run the sample model:
	Double-click on the Cyrillic 2.1 Breast Cancer Example icon created during the installation of the Cyrillic program - The icon contains pre-set commands necessary to run the Breast Cancer model.

	Open the sample file BRCA.FAM using the File\|Open command.

	Choose Data\|Run BrCa - Breast Cancer susceptibility

	In the MLINK Export dialog, type a filename for the MLINK file that will be generated by the Breast Cancer module - The default is MLINK.PRE. Ensure that the 'Run Program', 'Rewrite Locus file' and 'Rewrite pedigree file' options are checked and that the .PRE file will be saved into the directory which also contains the MLINK.EXE file. Click OK. (Note, this step is only necessary the first time this option is run. It may not be necessary if you have previously run MLINK)*

	Cyrillic will now run the Breast Cancer model automatically. Your screen will briefly switch to the MS-DOS Command prompt as MLINK runs. When MLINK has finished running press any key to switch back to Windows. The cumulative cancer risks will now appear in a floating palette. If you wish to paste these risks onto your pedigree, check the 'Create Annotation' checkbox and hit Close, select the Tools\|Annotation command and click at the point on your pedigree where you wish the risk information to be pasted. The Annotation dialog appears with all the information from the floating Cumulative Cancer risk palette already added, ready for you to paste into your pedigree.

Note that if you edit a risk locus such as the BrCa Breast susceptibility disease (Data\|Diseases... Edit), ensure that you never change its Risk Locus setting to either Affected or Quantitative - If you do so, all of your defined penetrance functions data will be lost.

Cyrillic 2 allows calculation of familial risks for breast cancer using the in-built Claus model data set (Claus EB, Risch N, Thompson WD. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 1991; 48: 232-42.) and the LINKAGE shareware software suite.

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