Imputation For Missing Snps By Mach

Question

[haoxiaokenuaa]

I did the inputation for missing SNP by MACH with the panel "hm3_r2_b36_fwd.CEU" or "CEU.r22.orig"

There was a FATAL ERROR——Please ensure that allele labels in pedigree are consistent with haplotype file...

It is confused me that whether the #snp(rsXXXX) in both my raw data and panel should be one-to-one correspondence. That is to say, they can not match the same label automatically.

How should I do In this case?

(1) Match the #snp(rsXXXX) manually?

OR

(2) Simply do it without panel mach1 -d sample.dat -p sample.ped --rounds 50 --states 200 --phase --compact

Please give some details about results of the two different methods above.Thanks

[zx8754]

BTW, it is iMputation not iNputation.

Answer 1

[zx8754]

From code we can guess that MACH throws this error when allele counts are more than 2, and --autoFlip is not switched on.

   if (errors && !autoFlip)
      error("Please ensure that allele labels in pedigree are consistent with haplotype file\n");

Preliminary Checks

Before genotype imputation, you should carry out basic data quality checks on available genotypes. Typically, we exclude from analysis markers that have low genotyping success rates (perhaps with <95% of genotypes called successfully), unexpected evidence for deviations from Hardy-Weinberg equilibrium (perhaps with an HWE p-value < 0.000001 or so), large numbers of discrepancies among duplicate samples or with several mendelian inconsistensies in available parent-offspring trios, or that are rare (with MAF < 1% or so). All these checks are platform and study specific, and you'll have to figure out what is appropriate for your data. They are mentioned here as a reminder...

When MACH loads your pedigree and the reference haplotypes, it checks that allele labels in the two samples are compatible and that allele frequencies are broadly comparable. If your sample includes no A/T or G/C SNPs (e.g. because it was genotyped on an Illumina Infinium platform), you can use the --autoFlip option to ensure that alleles in the pedigree file and those in the reference haplotypes refer to the the same strand. If your sample does include A/T and G/C SNPs, you'll have to ensure they are aligned to the same strand manually and inspect allele frequency discrepancies identified by MACH to help pinpoint problems. Although it is typical that a small number of SNPs will drift in frequency between populations, we recommend that you read through the warnings generated by MACH. If you see large frequency discrepancies or anything else suspicious ... investigate!

Newer versions of MACH will automatically ignore any SNPs that are present in your pedigree file but not in the reference panel. SNPs that are present only in the reference panel but not in your pedigree will be imputed!

Using --autoFlip option might resolve your issue.

This option flips alleles in pedigree file according to base pairing (A<-> T and C<->G) if >2 alleles are found when putting pedigree and reference together. Notice that it will not affect A/T or C/G SNPs as strand mismatch won't lead to more than two alleles.

[haoxiaokenuaa]

Thanks for your reply. Another question.

If I simply do it without panel mach1 -d sample.dat -p sample.ped --rounds 50 --states 200 --phase --compact.

Can I get the general results of the inputation SNPs compared with the one through panel?

[sunil.mahurkar]

Hi haoxiaokenuaa,

I was wondering if you were successful in solving the above problem, I am also encountering similar problems while imputing some untyped SNPs. Can you please let me know how you solved the error.

Many thanks and look forward to hear back from you.

Best ~