Linkage With Whole Exome Data

Question

[Biomed]

Is it possible to do linkage analysis using whole exome data only (i.e. without using micro array data)? I would like to use whole exome sequence from small pedigrees (i.e children and parents) and be able to perform linkage analysis. I am mainly interested in defining haploblocks, homozygosity mapping, linkage regions detection etc. Would PLINK be an option for this ?

[Zach Stednick]

I am interested in where you are headed with this. Could you please expand your question?

[David Quigley]

I think the point of confusion is that biomed means "SNP microarray", not "expression microarray". Unless the intent is to do eQTL analysis using RNA-seq, in which case you should look at Johnathan Pritchard's recent papers.

[Khader Shameer]

AFAIK, you don't need microarray data for linkage analysis. Are you looking at genetic linkage analysis or visualization of LD blocks ? You may use tools like PLINK, MapMaker or Haploview.

[Giovanni M Dall'Olio]

linkage between exons? I don't understand the question.

[Biomed]

the question is not about linkage between exons but performing linkage analysis using whole exome data

[ammar.husami]

I persume you referring to variants or (SNPs) found from exome sequencing. Be careful as adding 10-15% error rate may not be tolerated for linkage. My problem with exome data is you have to use good quality data so not to loose your linkage power.

Answer 1

[Hanif Khalak]

We're also thinking of using exome data to map loci - the idea seems reasonable:

1. sequence exomes
2. map both existing and new SNPs and corresponding genotypes across all samples
3. construct custom genetic map file of markers from (2)
4. format genotype data as a matrix similar to that obtained from microarrays (e.g PED file)
5. run standard linkage / homozygosity mapping tool (Allegro, GeneHunter, etc)

PLINK does find ROHs (regions of homozygosity) but doesn't seem to do standard linkage. This paper describes how PLINK does "population-based linkage" based on analysis of shared IBS segments.

Answer 2

[glyamamoto]

I have found this article and website interesting... http://bioinf.wehi.edu.au/software/linkdatagen/#mps http://genomebiology.com/2011/12/9/R85/

Will try it out and compare with our snpArray linkage in 4 patients (2 families)