A short tutorial for familias

Introduction

 

Familias is a program for computing probabilities for pedigrees. We assume one has measured the alleles of two or more persons at some loci, and that the frequencies and other properties of these alleles in the general population are known. The likelihoods of different pedigrees can then be computed. If a prior distribution on the possible pedigrees is given, the posterior is output. The program can even generate lists of possible pedigrees, based on user input.  

 

The data can  be input into the program interactively and saved to a file. This file can then be loaded later. It is also possible to read a database of allele systems and furthermore the data for a specific case. Complete details on how this is done are provided in the manual available from http:\\www.nr.no\familias .

 

At the end, a report giving an overview of the computation may be generated.

Overview of use

A standard use of the program will consist of the following steps:

  1. Add data about the allele system frequencies and properties by clicking on the icon depicting a document. It is smart to save this data to a file before continuing, for later re-use. 
  2. Add the relevant persons, that is, the persons for whom you have DNA data, and possibly some additional persons that are needed to define specific relationships between these. This is done with the person form, obtained by clicking on the yellow face on the tool bar.
  3. Add the fixed, known relationships between the persons added in the previous step. This is done with the fixed relations form, obtained by clicking on the red and yellow icon on the tool bar.
  4. Add the DNA information for the persons in this particular case, by clicking on the next icon (the lab tray).
  5. At this point, it is again smart to save your data, possibly to a differently named file. 
  6. You are now ready to consider the alternative pedigrees, using the last icon on the tool bar. You may either input the alternative pedigrees manually, or get the program to generate possible pedigrees for you, and select those you consider possible from this list. Then, a prior is computed for this list of pedigrees, and a posterior, using the DNA data, is computed. The results may be written out in a report.

An example

 

The easiest use for the program is for standard paternity cases. However, here we present a more complex example. A woman M has 3 sons S1, S2, and S3, and the question is if a putative father PF is the father of all, some, or none of these sons. DNA data is available for S1, S2, S3, and PF. Data from 8 loci is given. In all loci, all alleles have frequency 0.05. The alleles observed in the data are numbered 1,2,3,4. With this notation, S1, S2, S3 and PF have observations given in the table below:

 

Locus

S1

S2

S3

PF

1

1,2

3,4

3,4

1,3

2

1,2

3

1,2

2,3

3

1,2

3,4

1,2

1,4

4

1,2

3,4

3,4

1,4

5

1,2

3,4

3

1,3

6

1

1,2

3

1,3

7

1,2

1,2

3,4

2,3

8

1,2

2,3

3,4

2,3

 

Let us start with entering the general allele information. Click on the icon looking like a rolled-up document, and the “General DNA Data” form appears. This form gives an overview of the allele systems entered. To enter a new system, click on “Add”. The “Allele system” form appears. Each of the alleles in the system must be entered by entering a name and a frequency in the lowest fields, followed by clicking “Add”. Fa,ilias 1.6 requires allele frequencies to sum to 1. It is convenient to add an extra allele for each system to secure that this property holds, otherwise familias will scale the frequencies to add to 1. Note that the tab button may be useful. When the four alleles 1,2,3,4 and an extra allel, called, say, ‘Extra’, have been entered, click on OK, and the system appears in the “General DNA Data” form. Continue with the other 7 systems. At this point, it may be a good idea to save the current information entered to a file. This is done by clicking on the floppy disc icon.

 

We continue with entering the relevant persons. Start by clicking on the yellow and green face icon. The “Persons” form appears. Write in “S1” in the “Person” field, check “Male”, and “Is Child”. Checking the “Is Child” box guarantees that when pedigrees are later generated, none are generated where this person has children. The “Year of Birth” box may be left open; if a year is given, it is only used to influence the set of pedigrees later generated. Click “Add”, and go on to enter S2, S3, M, and PF in a similar fashion. Note the following trick: If you enter Year of Births for M and PF that are less than 12 years apart, no pedigrees will later be generated where one of these is a parent of the other.

 

To enter the known relations between M and her three sons, use the “Known Relations” form, which appears by clicking the icon with the red circle and square. We then go on to the stage where the DNA data is entered. Click on the blue lab dish icon. The “Case-Related DNA Data” form appears. To enter data for a person, double-click on that person. Each observation must be entered by writing in, or choosing, the system name, and the two allele names, followed by clicking “Add”. If only one allele has been observed for a person in a system, that allele must be entered twice. Click “OK” when all information for this person has been entered. You can always go back and add or remove data later. After you have added your data, it is again smart to save the work you have done to some file, using the “Save as” choice from the “File” menu.

 

We are now ready to generate the relevant pedigrees for which we would like likelihoods computed.

We start by clicking on the icon with the multicolored rings, and the “Pedigrees” form appears. One way to generate the pedigrees is to do it manually, using the “Add” button on the “Pedigrees” form. It produces a form called “Pedigree”, where the relationships can be entered. Extra persons needed to define specific relationships can be entered by clicking on the “Persons” button on the form. To avoid this manual work, we can instead use the “Generate” button on the “Pedigrees” form. Click it, and keep the default settings of no extra males or females. Eight pedigrees are generated, assuming you have entered the person data as suggested above.  To inspect a pedigree, double-click on its line in the “Pedigrees” form. Note that the number of possible pedigrees increases extremely fast with the number of extra persons introduced. Even small numbers of extra persons can cause the program to continue with computations for hours, and unfortunately, the only way to stop it is to terminate the “familias” program. This is one reason why it is a good idea to always save your data before you start the generating function.

 

To compute probabilities (a prior and a posterior) for the generated set of pedigrees, click on the “Probability” button on the “Pedigrees” form. The first four fields have to do with how the prior is computed. The default parameters will generate a flat prior, where all pedigrees have the same prior probability. Reducing the “Generations parameter” towards zero will reduce prior probability of pedigrees with many generations, and “Max generations” may, when different from 0, reduce the possible number of generations. Reducing the “Inbreeding parameter” reduces the prior probability of inbred pedigrees, and similarly with the “Promiscuity parameter”. If you click “No” in the “Use case-specific DNA data”, only the prior will be computed. If you click “Yes”, the posterior will be computed.

 

We leave the box unchanged, and just click “OK”. The posteriors are computed, and we see that the pedigree where PF is the father of S3, but not of S1 or S2, is the most likely. Use the “Likel” button to study the relative likelihoods of the pedigrees, and the “scale” button to scale all values in proportion to one chosen pedigree.

 

To generate a report, click the “Report” button on the “Pedigrees” form. A box with the contents of the report appears. Note that the report will list the pedigrees selected in the pedigree list. In order to print it out, you must first save it to a file, using the “Save” button at the bottom of the “Report” form. Then, the resulting file must be opened with a separate program, e.g., “Word”, and edited and/or written out from that program.