Method

Infered IBD sharing across a chromosome for a sib pair estimated using affy 500k data

This method estimates the probability of sharing alleles identity by descent (IBD) across the genome and can also be used for mapping disease loci using distantly related individuals. These individuals will often be seemingly unrelated but if they share the same founder mutation then they will be distantly related. The method is based on a continuous time Markov model with hidden states. The hidden states are the IBD states between a pair of individuals with diploid chromosome. We assume that the individuals are not inbreed and thus the individuals can share 0, 1 or 2 alleles IBD. The SNPs are allowed to be in linkage disequilibrium (LD). To accommodate LD the methods need SNP for several individuals in order to estimate the allele frequencies and the pairwise LD. The method return the posterior probabilities of the IBD states across the genome and the overall IBD sharing. The estimates for all pairs of individuals can be combined info a score that will show linkage peaks across the genome and using a permutation procedure a significance threshold can be set. I recommend using the R package for fast visualization of a single pair of individuals (see figure).

Download and Installation

Software version 0.9992

So far this implementation is supplied as an R package for both windows and unix.

The method is implemented in an R package and as a commandline based C++ program embeded in the R package. The R code can be used to find and visualize the tracts of relatedness between a pair of individuals. The commandline version has under 20% of the running time when running all pairs compared to a single pair, it however has the the same speed for running a single pair analysis. For analysis linkage only the C++ version is implemented.

There is also a precompiled R-package for windows that can be downloaded here.

To compile the C++ version: unpack the R package; go to the scr folder that contains the C++ files; type

 ./install.sh

windows users might have to type in the commands in the contents of ./install.sh' file manually if they don't have bash installed. (Just 3 commands).

Manual

See the manual.pdf in the download for in-depth information about installation, method and examples.

If you have any problems or comments please contact me albrecht @ binf.ku.dk

Citation

Anders Albrechtsen, Thorfinn Sand Korneliussen, Ida Moltke, Thomas van Overeem Hansen, Finn Cilius Nielsen, Rasmus Nielsen. Relatedness mapping and tracts of relatedness for genome-wide data in the presence of linkage disequilibrium. Genet Epidemiol. 2009 Apr;33(3):266-74

Bibtex

  % 19025785 
  @Article{pmid19025785,
  Author="Albrechtsen, A.  and Sand Korneliussen, T.  and Moltke, I.  and van Overeem Hansen, T.  
  and Nielsen, F. C.  and Nielsen, R. ",
  Title="{{R}elatedness mapping and tracts of relatedness for genome-wide data in the presence of linkage disequilibrium}",
  Journal="Genet. Epidemiol.",
  Year="2009",
  Volume="33",
  Number="3",
  Pages="266--274",
  Month="Apr"
  }

pubmed

19025785

table 1

There is an error in table 1 in the article. It should have said

$G_{i}^{j,k}$	$X_{i}=0$	$X_{i}=1$	$X_{i}=2$
AA AA	$p_{A}^{4}$	$p_{A}^{3}$	$p_{A}^{2}$
AA aa	$2p_{A}^{2}p_{a}^{2}$	$0$	$0$
AA Aa	$4p_{A}^{3}p_{a}$	$2p_{A}^{2}p_{a}$	$0$
Aa Aa	${\boldsymbol {4}}p_{A}^{2}p_{a}^{2}$	$p_{A}^{2}p_{a}+p_{A}p_{a}^{2}$	$2p_{A}p_{a}$

The difference in the 4 shown in bold

Change log

Version 0.997

fixed a rare underflow problem fixed a problem for R version 2.15
Version 0.995

Removed some NAMESPACE stuff that did not work on 2.13.0
Version 0.993 (3 april 2010)

added another linkage example with plot
Version 0.992 (18 jan 2010)

made compatable with gcc 4.4.1
Version 0.99 (12. april)

Yet another fantastic release!

Program uses much less memory know, and various bugs has been written. (See CHANGELOG in package for elaborate info)

The manual has been updated.

version 0.987 (24. feb 2009)

A milestone release! This version has been very much anticipated

Program can read plink binary files (R & commandline)

Program can read pedfiles,using the 'snpMatrix' package (R only)

Testfiles and examples are included

A thoroughly manual is included, or can be downloaded here manual.pdf

(subversion 0.98* are bugfixes for 0.98)

version 0.95

Much faster when performing linkage analysis in the C++ inplimentation (all pairs)

If chromsome number is given the programs sorts the SNP accordenly

version 0.83

version 0.802: apparantly the uint datatype doesn't exist in older compilers, So now a macro is added that defines the unsigned int if the gcc is older than 4.3

Relate

Contents