how to calculate LOD scores for NGS results?

[Lilach]

Hi,
I have NGS results (whole exomes, VCF files) for several family members with the same disease, and also the parents that are healthy.
Is there an available algorithm to calcultae LOD scores for linkage of variants to the disease? I.e. I would like to have the LOD score for each variant.
Or any other way to find the locus/loci associated with the disease.
Because I'm not sure the responsible mutation is realy in the exome (maybe it is intronic, or a long indel, or in an uncovered exon, etc).

Thanks!

[AJERYC]

Hi,
I have NGS results (whole exomes, VCF files) for several family members with the same disease, and also the parents that are healthy.
Is there an available algorithm to calcultae LOD scores for linkage of variants to the disease? I.e. I would like to have the LOD score for each variant.
Or any other way to find the locus/loci associated with the disease.
Because I'm not sure the responsible mutation is realy in the exome (maybe it is intronic, or a long indel, or in an uncovered exon, etc).

Thanks!

I dont think LOD score would be useful in this regard since you would need a very extensive family unless you are studying a recessive disorder Besides with NGS you get so many data that would generate a lot of false positives. I would sugggest to look for homozygosity sharing regions or ibd larger regions which may content the causative mutation.
Eitherway if you want to go with LOD score calculation try to get 1,000,000 random samples of SNPs distributed as evenly as posible in the exome and calculate LOD scores using Merlin. There may be additional setbacks such as linkage disequilibrium among samples, and that exomes are not ment to capture intron information and SNPs are more common intronic.

[vmrosario]

Did you already look at identical variants in the affected individuals in the same family? Maybe they have the same mutation?