I need an advice concerning determining haplotypes small pedigrees/nuclear families, using next gen sequencing (whole exome) data.
I have whole exome data from families with mother, father and between one and in the best case 4 children. I also have Illumina infinium chip data on all of the individuals.
I am mainly interested in determining the haplotypes using next gen sequencing data but any robust method that may also integrate chip genotype data and whole exome data would be valuable as well.
We have some experience with ENT but many other tools were mentioned before (i.e. http://biostar.stackexchange.com/questions/551/reconstruction-of-haplotypes-from-the-genotypes-on-snps ) Can you please advise on how to best approach this problem?
Perhaps I am being naive, but wont haplotype construction from an exome capture experiment be rather limited? You are only capturing exons, which are typically on the order of 100-500bp, and most exons contain no polymorphism. To discern a haplotype for a single individual at a single exon, would you not need at least two heterozygotes and reads or pairs of reads that cover both sites? Otherwise, you'll be left without clear evidence of which alleles are on the same haplotype.
In other words, it is conceptually possible, but my feeling is that you only have power to do the directly from you capture data for a very small portion of the exome.
It seems that someone addressed this question. There is a new methodology using whole-exome to call haplotypes and look like promissor.
Accurate local-ancestry inference in exome-sequenced admixed individuals via off-target sequence reais. Hu, Youna; Willer, Cristen; Zhan, Xiaowei Kang; Hyun Min; Abecasis, Gonçalo R. American journal of human genetics. 2013