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7.1 Introduction to ibddrop
7.2 Sample ibddrop
parameter file7.3 Running ibddrop
example and sample output7.4 ibddrop
statements
See Concept Index for: a priori ibd probabilities, identity by descent, ibd.
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ibddrop
ibddrop
estimates probabilities of gene identity by descent, ibd,
(such as kinship, inbreeding, or multi-gene identities) by Monte Carlo in the
absence of data. Given the pedigree and a genetic map, ibddrop
simulates
meioses indicators and scores them to estimate the ibd probabilities among a
set of gametes.
The simplest example of estimation of ibd probabilities among a set of gametes is the computation of an individual's inbreeding coefficient. In this example, the set of gametes in question are the maternal and paternal gametes that make up the individual. A set of two gametes can be either ibd or not-ibd. To keep track of ibd status among the gametes, we can label the paternal allele `1'. If the two alleles are ibd, the maternal allele would also be labeled `1', and the resulting ibd pattern would be `1 1'. If the two alleles are not ibd, the maternal allele would be labeled `2' and the resulting pattern would be `1 2'. The individual's inbreeding coefficient is the probability that the two alleles follow the `1 1' pattern.
If there are three gametes in the set, there are five potential ibd
patterns: `1 1 1' (all three gametes are ibd), `1 1 2' (the first
two are ibd and the third is not), `1 2 1' (the first and third are
ibd) , `1 2 2' (the last two are ibd), and `1 2 3' (none are
ibd). ibddrop
can estimate probabilities of ibd patterns among
up to 10 gametes in a set. ibddrop
outputs a probability for each
ibd pattern at each marker.
Gene identity can be scored either for each locus separately, in which patterns
of identity among up to ten haplotypes can be scored, or it can be scored
jointly over a moving window of several loci. If the moving window option is
selected, genedrop
calculates the probability that the specified pair of
gametes are ibd at all loci in the window. As a result, it is then possible
to determine the probability that all or some of the gametes are ibd for a
particular haplotype.
See Concept Index for:
ibddrop
introduction,
ibd pattern,
meiosis indicators,
inheritance indicators.
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ibddrop
parameter file
Files for ibddrop
may be found in the `IBD' subdirectory of
`MORGAN_Examples'. The sample parameter file for ibddrop
is
`jv_rep_ibd.par'.
set printlevel 5 input pedigree file 'jv_rep.ped' simulate markers simulate tloc 1 map markers distances 44.6 44.6 11.2 11.2 map tlocs 1 marker 2 distances 22.3 set component 1 proband gametes 331 0 333 1 set component 2 proband gametes 541 0 541 1 341 0 343 1 input seed file '../sampler.seed' set MC iterations 20000 |
The parameter file specifies the pedigree file name `jv_rep.ped' and then
asks for five markers and one trait locus. Since there are no data, the
distinction between marker and trait doesn't mean anything -- it is just a way
to specify a set of loci, one of which may be unlinked. `jv_rep.ped'
contains data on 30 individuals, including gender and one trait. The reason
for this specification is that the same specification may then be used in
lm_auto
, where simulation is conditional on marker and (optionally)
trait data. See Estimating Conditional IBD Probabilities by MCMC.
The two `map' statements specify the genetic map. From the first statement, the genetic distances between the markers are 44.6, 44.6, 11.2 and 11.2 centiMorgans. From the second statement, the trait lies between markers 2 and 3, at 22.3 centiMorgans with marker 2.
The `set proband gametes' statements tell ibddrop
which gametes to
score: that is, the gametes among which the ibd probabilities will be
estimated. In this example, we selected, from component 1 (the first family in
the data set), the maternal (0) gamete of `331' and the paternal (1) gamete
of `333'. The next statement selected four gametes to score from family 2.
Note that characters are allowed in the names of individuals.
The `input seed file' statement enables the file to use the seeds from file `sampler.seed'. The `output overwrite seed file' statement allows the program to replace the contents of the seed file with the newly generated seeds. If this options were omitted, when the program finished running, new seeds would be appended to the end of the file. Seeds can also be set using the `set sampler seeds' statement (see ibddrop statements).
The number of Monte Carlo iterations is set to be 20,000 by the `set MC iterations' statement.
Note that if one would like to compute a
multilocus ibd probability, the statement
`set locus window' can be used to specify number of loci to score
jointly. ibddrop
has limited functionality for computing
multilocus probabilities, it can only examine two gametes to determine whether
or not the two are ibd. For instructions on how to implement windows in this
example, see the parameter file. For additional options, including specific
patterns over two or more gametes, see Sample lm_auto parameter file:
lm_auto
has the option of scoring more general patterns
of gene indentity over multilocus windows.
See Concept Index for:
ibddrop
sample parameter file,
Haldane map function,
proband gametes,
seeds for sampler,
seed file.
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ibddrop
example and sample output The syntax for running this MORGAN program is:
<./program> <parameter file> [ > <output file name> ] |
where , optionally, `>' redirects the standard output (<stdout>) to an output file instead of to the screen.
The `ibddrop' example can be run under the subdirectory `IBD/' with the following command:
./ibddrop jv_rep_ibd.par > ibddrop.out |
The genetic map specified by the statements `map markers distances' and `map tlocs 1 marker 2 distances' is below. Note the position of the trait locus (T1) with respect to the marker loci.
Distances (cM): T1 --------------+--------------------- 44.6 22.3 22.3 11.2 11.2 +------+-------------+------+------+ M1 M2 M3 M4 M5 |
Since the parameter file contains two `set proband gametes' statements,
ibddrop
will produce two sets of results in the output file (here
`ibddrop.out').
The exact probability estimates will, of course, depend on the random seed used. Some example results for the second component are detailed below.
Summary for component 2: Probabilities of IBD patterns Proband gamete set 1: 541 0 541 1 341 0 343 1 pattern marker-1 marker-2 tloc-1 marker-3 marker-4 marker-5 label 1 1 1 1 .0290 .0293 .0285 .0284 .0295 .0298 0 1 1 1 2 .0271 .0298 .0285 .0294 .0288 .0283 1 1 1 2 1 .0144 .0126 .0130 .0146 .0135 .0140 3 1 1 2 2 .0095 .0107 .0106 .0093 .0092 .0089 4 1 1 2 3 .0249 .0258 .0278 .0273 .0280 .0268 5 1 2 1 1 .0693 .0644 .0664 .0654 .0659 .0633 6 1 2 1 2 .0063 .0053 .0056 .0060 .0055 .0052 7 1 2 1 3 .0599 .0605 .0585 .0585 .0597 .0585 8 1 2 2 1 .0693 .0693 .0698 .0696 .0708 .0712 9 1 2 2 2 .0495 .0479 .0489 .0490 .0490 .0471 10 1 2 2 3 .1406 .1384 .1338 .1372 .1363 .1392 11 1 2 3 1 .1376 .1368 .1401 .1364 .1374 .1391 12 1 2 3 2 .0251 .0263 .0297 .0255 .0265 .0279 13 1 2 3 3 .0956 .0958 .0961 .0976 .0954 .0958 14 1 2 3 4 .2418 .2472 .2427 .2459 .2447 .2451 15 |
The probabilities are summarized by the ibd pattern. Each integer in the
pattern represents one of the gametes that ibddrop
was asked to score.
Same numbers indicate gametes that are ibd. For instance, `1 1 1 1'
means all four gametes are ibd; `1 2 1 1' means gametes 1, 3, and 4 are
ibd, while gamete 2 is not ibd with the others; `1 2 3 4' means all
four gametes are not ibd.
The ibd patterns are scored for each locus separately; there is a column for each of the five markers and one for the trait locus.
To compute multilocus ibd probabilities, say for 3 loci, follow the instructions to use `set locus window 3' in the parameter file and re-run the example using the same command line. The interesting part of the output is:
Summary for component 2: Probabilities of IBD patterns for windows of 3 loci Proband gamete set 1: 541 0 541 1 IBD wndw 1 wndw 2 wndw 3 wndw 4 0 0 0 .7291 .7443 .7657 .7881 0 0 1 .0698 .0655 .0482 .0478 0 1 0 .0640 .0532 .0365 .0266 0 1 1 .0279 .0252 .0369 .0284 1 0 0 .0806 .0696 .0703 .0493 1 0 1 .0087 .0080 .0067 .0049 1 1 0 .0135 .0238 .0177 .0268 1 1 1 .0063 .0105 .0180 .0281 |
This time, ibddrop
was asked to compute ibd probabilities in windows
of three loci at a time. This was done using the `set locus window'
statement. Since the trait locus is unlinked to the marker loci in this
example, it is placed to the left of the five marker loci on the map. Thus the
first window, `wndw 1' in the table above, includes the trait locus and the
first two marker loci, `wndw 2' includes the first three marker loci,
`wndw 3' includes marker loci 2, 3 and 4, etc. The values in the
`ibd' column at the left of the table represent `ibd' patterns. The
pattern `0 0 0' means that the selected gametes are not ibd at the
three loci in each window. The pattern `0 0 1' means that the selected
gametes are not ibd at the first two loci in the window, but are ibd at
the third. The values in the columns give the probability of the ibd
pattern at the left for each of the four windows. For example, the probability
that the maternal and paternal gametes of individual 541 are ibd at marker
loci 3 and 5, but not at marker locus 4 is 0.0049.
Note that there are two additional example parameter files in the `IBD/' subdirectory; these examples are not discussed in the tutorial but are there for the interested user.
See Concept Index for:
running ibddrop
example,
ibddrop
sample output,
ibd pattern.
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ibddrop
statements
Note that ibddrop
does not simulate or use marker or trait data. The
statements are used only to specify the map of the loci at at which descent is
to be simulated and ibd scored. The locations of loci are specified in this
way so that direct comparisons can be made between output of ibddrop
and
of lm_auto
(see Running lm_auto example and sample output), where
simulation is conditional on marker and trait data.
The additional ibddrop
statements are:
simulate markers
simulate tloc L
simulate markers
statement,
establishes the trait locus to be simulated. Note that this trait locus must
be mapped onto the chromosome selected for marker simulation.
map tlocs L1 ... unlinked
set [component M] proband gametes N1 K1 N2 K2...
In this statement, the user specifies which gametes ibddrop
is to score.
Each statement must contain gametes from a single component, as the components
are assumed to be independent, i.e. the probability of ibd between gametes
from different components is zero. Pairs consisting of an individual's name and
a meiosis indicator are listed, with `0' indicating the individual's
maternal gamete and `1' indicating their paternal gamete.
In the current version of MORGAN, the number of proband gametes in a set is limited to 10.
set [chromosome I] locus window K
This statement gives the window size (number of loci) for which the multilocus ibd probabilities are scored. If no size is given, each locus is scored separately.
set sampler seeds H1 H2
This statement initializes a pair of seeds for the random number generator. The seeds must be positive and no greater than `0xFFFFFFFF', with the first seed (congruential seed) odd, and the second seed (Tausworthe seed) nonzero. If no seeds are specified, default seeds are used.
set MC iterations I
See Concept Index for:
ibddrop
statements,
proband gametes,
meiosis indicators,
inheritance indicators,
seeds for sampler.
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