Web & text
You must supply the initial data file to CRI-MAP. It is a plain
"ascii" text file that may be created and edited in almost any
word-processing programme. chr#.gen
data files always have the form:
(Section 1, with info for the entire pedigree collection:)
# of families # of loci locus_name1 ln2 ln3 etc. (NB: locus names have a 15 character limit)
(Section 2, with the pedigrees:)
(Section 2.1-f, with general info for the first family:)
family 1 id (any unique name or number designation) # of family members
(Section 2.1-i, with the data for each individual from the first family:)
individual 1 id# mother's id# father's id# sex id# locus_name1allele1# ln1a2# ln2a1# ln2a2# etc. individual 2 id# mother's id# father's id# sex id# ln1allele1# ln1a2# ln2a1# ln2a2# etc. etc.(Section 2.2-f, with general info for the second family:)
family 2 id # of family members
(Section 2.2-i, with the data for each individual from the second family:)
individual 1 id# mother's id# father's id# sex id# locus_name1allele1# ln1a2# ln2a1# ln2a2# etc. individual 2 id# mother's id# father's id# sex id# ln1allele1# ln1a2# ln2a1# ln2a2# etc. etc. and so on ...
The manual shows this short generic example.
Points to note:
Chromosome 37 Loci Locus Name allele (code #) allele (code #) allele (code #) A a (1) A (2) B b (1) B (2) C c (1) C (2) c* (3) D d (1) D (2) d* (3) E e (1) E (2)
NB: When using your own data, if they are already in the correct format for analysis by the Linkage suite of programmes, you may convert them to CRI-MAP chr#.gen format with the LNKTOCRI utility.
With the chr#.gen file written, you submit it to the prepare option of CRI-MAP to create standard versions of the auxilliary data files. ALL CRI-MAP options are applied to datafiles with commands of this form:
prompt> crimap # option
For example, to perform "twopoint" linkage analysis on data for chromosome 12 (you will already have datafiles named chr12.gen, chr12.dat, chr12.loc, chr12.ord, & chr12.par), the command is:
prompt> crimap 12 twopoint
The programme then responds by displaying the results of the analysis on the screen. Unlike most other CRI-MAP options, however, prepare is an interactive one; before it completes the preparation of the auxilliary datafiles, you must reply to a series of questions, mostly having to do with accepting default values for various parameters and filenames used in the analytical options.
NB: If you see the warning:
NONINHERITANCE: family "fam_name", individ id#, locus #
your chr37.gen file has an error!
Although we have chosen build as the next option to run, first examine
the structure and the content of the datafiles just created from the chromosome
37 pedigrees. These datafiles summarise different aspects of the data and
details of the subsequent processing by CRIMAP.
Genotype file chr37lmn.gen Number of loci: 5 #inf. mei. #inf. mei.(phase known) 0 A 3 3 1 B 3 3 2 C 7 3 3 D 11 0 4 E 4 0
Traditionally, an informative meiosis is one that, firstly, leads
to offspring, and secondly, occurs in a parent who is (usually) at least
a double heterozygote. In Family
LMN.3, the grandfather is a triple heterozygote who produces four children.
Thus, he yields four informative meioses (one per child) for each of the
three loci: C, D, & E. His son who is a triple heterozygote (loci A,
B & C) produces three children, thus yielding three informative meioses
for each of these three loci. Summing up, the totals are: A-3, B-3, C-7,
D-4, & E-4. Why then has locus D eleven informative
meioses, according to CRI-MAP?
The prepare option has determined that both the grandmother and
the son's partner - even though they are only single heterozygotes - also
provide informative meioses for the D locus. There are four meioses in the
grandmother (her four children) plus three more from her son's partner.
This adds the extra seven informative meioses for locus D.
Note that the informative meioses from the son are also phase known. This means that we know which set of five alleles for these five loci came from each parent. We know the original allele complements (phase) of his two chromosomes. He received a chromosome with alleles A b c* d E from the grandmother, and another with alleles a B C d E from the grandfather. Knowing the phase of the chromosomes reduces the number of possible original-states the programme must explore in its analysis, thus speeding result and increasing its accuracy.
1 1 2 2 0
As you acquire new data, you may add it to existing data files automatically. merge allows the addition of data when either loci or families are shared between separate chr#.gen files.
For example, we could increase the amount of phase known information for the chromosome 37 dataset if we knew the genotypes of the parents of the two males who "bred into" family OPQ.7 .
NB:You will see warnings similar to:
MISMATCH IN PEDIGREE 537728400, individual 7 MISMATCH IN PEDIGREE 537728400, individual 8The chr37OPQ.gen file has no error - these two individuals are the two males who have just had their parents added to the pedigree. As such, their "mother's id#" & "father's id#" values change from "0" (unknown) to one of the four new pedigree members.
What additional information is now available to CRI-MAP? A quick way to check is to compare the chr37.loc file with the new chr37a.loc file you can create via the crimap 37a prepare command.
Note that locus E is now reported as being more informative than locus D by the prepare option output. Comparison of chr37.loc with chr37a.loc shows four more informative meioses overall, 10 more being phase known, and three of these new phase known meioses occurring at locus E.