MERLIN - Frequently Asked Questions
- How do I reference MERLIN?
To reference MERLIN, please cite: Abecasis GR, Cherny SS, Cookson WO and Cardon LR
(2002). Merlin-rapid analysis of dense genetic maps using sparse gene flow trees.
Nat Genet 30:97-101.
- Why should I register my copy of MERLIN?
Well, all software programs are buggy... and MERLIN is probably no exception. If we find something
wrong, we need your e-mail address to let you know. This information is also used to gauge the level
of interest in the project and helps decide whether to invest time making MERLIN even better or,
perhaps, go back to the lab and do some real work.
- Do I need a license to use MERLIN?
MERLIN is available free for both commercial and non-commercial use, no license is required.
However, note that no redistribution of the MERLIN source code or binaries is allowed. If you do use
MERLIN, please register.
- What is the meaning of a negative non-parametric LOD score?
A positive non-parametric LOD score indicates excess allele sharing among affected
individuals (for discrete traits) or individuals with similar phenotypes (for quantitative
traits). A negative non-parametric LOD score indicates less than expected allele sharing
among these groups of individuals. Under the null, the average LOD score should be zero
and an excess of negative LODs suggests that the data contain genotyping errors and/or
- Can I send MERLIN output to a file?
To direct MERLIN output to a file, you can either redirect output to
a file, with the ">" redirect operator, e.g.:
prompt> merlin -d datfile -p pedfile -m mapfile > outfile
Or, in standard Unix systems, pipe MERLIN output through tee:
prompt> merlin -d datfile -p pedfile -m mapfile | tee outfile
To get output both to the screen and a file. When redirecting
output, the --quiet option is recommended!
- What are the different quantitative trait analysis options?
MERLIN supports three different types of analysis for quantitative traits:
What causes the message "SKIPPED: Requires impossible recombination pattern
Variance components analyses (--vc option), can incorporate
user-specified covariates (--useCovariate option), and are designed
for unselected, normally distributed traits. For other phenotypes,
their interpretation usually requires simulation.
Pedigree wide regression analysis (implemented in MERLIN-REGRESS)
is suitable for traits that are approximately normally distributed in the
population, even after selection. This method requires specification of
the trait mean, variance and heritability in the population. In large samples,
the central limit theorem ensures good control of type I error even for
Non-parametric analyses (--qtl and --deviates options) look
for excess sharing among individuals in the same tail of the
trait distribution. These analyses make no assumptions about the trait
distribution and are the most widely applicable, but have low power for
normally distributed traits. Within each family, more extreme individuals
are given greater weight. A more detailed
description of these two statistics is available.
This message appears when the pedigree likelihood becomes zero. The most likely causes
are that there is an obligate recombination event between two markers that map to the exact
same map position or that, when an approximate solution is requested, the number of recombinants
between consecutive markers in a pedigree exceeds the user specified limit.
The best way to solve this problem is to edit the map file (or recombination fractions, if you
are using LINKAGE format input files) to ensure that every marker maps to a unique position.
How does the --simulate option work?
This options generates random marker data through gene dropping simulations. Details
are provided in the Merlin reference.
Can MERLIN carry out chromosome X analyses?
To carry out chromosome X analysis you should run MINX (MERLIN in X),
a separate executable which is included with MERLIN version 0.9.1 and above.
Presently, MINX is unpublished but believed to be correct. Use with care.
Is there a way to get the --perFamily results in merlin.lod
organized by family, rather than by location?
If you are running tcsh, and have the standard UNIX utilities cut, sort,
head, uniq and grep installed in your system (these utilities are present in
nearly all systems), you can try the following series of commands:
prompt> merlin -d datfile -p pedfile -m mapfile --perFamily ...
prompt> head -1 merlin.lod > sorted.lod
prompt> foreach family (`cut -c 1-10 merlin.lod | sort | uniq`)
foreach? grep -E "^ *$family " merlin.lod >> sorted.out
After running these commands, the results in the file sorted.lod will be organized by
family. As with other series of useful commands, you may be able to combine these into a
shell script in your ~/bin directory.
Can I analyse markers with more than 32 alleles?
Yes. Analysis of markers with up to 64 alleles can be enabled by including the option
-D__USE_LONG_INT in the CFLAGS line of the MERLIN Makefile and recompiling MERLIN. With
versions of MERLIN 0.9.6
and earlier the number of alleles is also the maximum allele size. Versions of MERLIN
0.9.7 and later only consider alleles that actually occur in the sample.
Can I disable testing of some markers, phenotypes or covariates without generating a
new pedigree file?
Yes! The simplest way to skip over a trait, covariate or marker during analyses is to make
a small edit to the data file, as follows: if you want to disable a particular covariate or
trait, replace the the "C covariate_name or "T trait_name" row in the data file with
"S covariate_name" or "S trait_name". The "S" label stands for SKIP COLUMN and the covariate
or trait will be ignored. If you want to disable a particular marker, replace the
"M marker_name" in the data file with "S2 marker_name". The "S2" label stands for "SKIP TWO COLUMNS".
How do I convert genotype data downloaded from the HapMap website into Merlin format?
One way to do this is to use the hapmapConverter program included in more recent versions of Merlin.
This program take a hapmap genotype (-g) and template pedigree file (-p) as input and
generates .dat, .map and .ped files in Merlin format. A examplar template pedigree file is included
in the examples subdirectory. The example file can be used with the HapMap YRI, CEU and JPT+CHB
analysis plates It is called HapMap.template.