A six generation consanguineous family with a skin disease that follow autosomal dominant inheritance pattern, SNPs of 11 members (7 affected and 4 normal) were performed.
I have analyzed the data with homozygositymapper, autoSNPa and dominantmapper but with no results for linkage?
Can anyone suggest for linkage analysis software?
Sequencing must be the best option in this scenario in order to find out mutations. Such rare diseases are always due to mutation that will not be detected by SNP chips. I am not sure how far u can dig the causative genetic variations for the skin disease in these patients with this data. Did you impute all the chromosomes?
Consanguinity is a confounder for linkage with dominant inheritance. To the extent that consanguinity is relevant to the disease locus, homozygotes for the disease variant will result in those affected individuals being uninformative. Similarly, homozygosity mapping is not likely to yield an informative answer if the trait is dominant. In the absence of homozygosity, the MLOD for 7 affected individuals is expected to be about 2.1 (depends on the pedigree structure, but a useful rule of thumb). You might consider performing some simulations with your pedigree to determine what the MLOD and ELOD for the pedigree are. You might never achieve significance with this pedigree alone.
Also, high-density markers do not help one much for linkage since all the markers in a region will be in linkage disequilibrium within the pedigree. One would want to employ some analysis program that utilizes Markov Chains to summarize the runs of non-informative markers (due to LD) into a haplotype.
The link is to a preprocessing pipeline for analyzing linkage using array markers. It seems that it uses other programs such as MLINK to actually do the analysis, so given my comment above, probably not the best approach.
https://www.dynacom.co.jp/u-tokyo.ac.jp/snphitlink/
Dear Saeed,
Simwalk2 software (Sobel&Lange, UCLA) is a best for linkage analyses with inbred loops if you have them in your pedigrees. There is also a SNPs based linkage analyses options. Simwalk2 is free software and user-friendly, except pedigrees formatting based on Fortran)) But I like this software, there are more options for IBD, Haplotypes, Mistyping etc analyses.
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