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All markers marked as duplicates in the final output

Sheldon89
2017-04-15
2017-04-15
  • Sheldon89

    Sheldon89 - 2017-04-15

    Hi Pasi and Lep-map users,

    I'm trying to use 4928 high quality SNPs (that were used to estimate linkage with Plink) to make a linkage map for my species. To give you a little bit more background, my species has 25 chromosomes and undergoes achiasmatic meiosis (no recombination in female) and I have genotype information from a mom and dad and their sixteen offsprings.

    So this is what I did.

    I took the ped file from plink, converted it to linkage format and then used Filtering, Separate Chromosomes, JoinSingles and OrderMarkers modules to get the linkage map.

    1) java -cp /data/programs/lepmap2/bin/ Filtering data=FaHetMoHom.linkage dataTolerance=0.001 >FaHetMoHom.f.linkage

    2) java -cp /data/programs/lepmap2/bin SeparateChromosomes data=FaHetMoHom.linkage sizeLimit=56 lodLimit=4.3 informativeMask=1 >map1.txt

    3) java -cp /data/programs/lepmap2/bin JoinSingles map1.txt data=FaHetMoHom.linkage lodLimit=3 lodDifference=1 >map1_js.txt

    4) java -cp /data/programs/lepmap2/bin/ OrderMarkers map=map1_js.txt data=FaHetMoHom.f.linkage chromosome=2 initRecombination=0.05 0 >order1.txt

    However, after running these steps in the final output, all markers came out as duplicates. For your reference, please find the first few lines of the input linkage file (only a few columns for six individuals) and output file (order1.txt), and the standard output for the modules below.

    It would really appreciate it if you could give me some pointers about what I'm doing wrong. Let me know if you need more details from my side.

    1) Input file

    family  1   0       0       1       0       2 1     2 1
    family  2   0       0       2       0       1 1     1 1
    family  3   1       2       0       0       1 1     2 2
    family  4   1       2       0       0       2 2     1 1
    family  5   1       2       0       0       2 2     1 1
    family  6   1       2       0       0       1 1     2 2
    

    2) Output file

    #java OrderMarkers map=map1_js.txt data=FaHetMoHom.f.linkage initRecombination=0.05 0 
    #*** LG = 1 likelihood = 0 with alpha penalty = 0
    #marker_number  male_position   female_position ( error_estimate )[ duplicate*]
    3878    0.00    0.00    ( 0.01 )
    3840    0.00    0.00    ( 0.01 ) duplicate*
    3900    0.00    0.00    ( 0.01 ) duplicate*
    3805    0.00    0.00    ( 0.01 ) duplicate*
    3978    0.00    0.00    ( 0.01 ) duplicate*
    3880    0.00    0.00    ( 0.01 ) duplicate*
    

    3) Filtering

    java -cp /data/programs/lepmap2/bin/ Filtering data=FaHetMoHom.linkage dataTolerance=0.001 >FaHetMoHom.f.linkage
    ***
    Mendel error statistics:
    0->0 : 0
    0->1 : 0
    0->2 : 0
           Error rate = 0.0
    1->0 : 0
    1->1 : 0
    1->2 : 0
           Error rate = 0.0
    2->0 : 0
    2->1 : 0
    2->2 : 0
           Error rate = 0.0
    0,2->0,2 : 77323
      0,2->1 : 143
    1,2->1,2 : 0
      1,2->0 : 0
           Error rate = 0.0018459711357240597
    Warning: there are Mendel errors
    ***
    Filtering markers based on segregation distortion
    Removed 97 markers from family family
    Maternally informative markers = 0 (of 4928)
    Paternally informative markers = 4831
    Maternally or paternally informative markers = 4831
    ***
    Removed 0 markers
    

    4) SeparateChromosomes

    java -cp /data/programs/lepmap2/bin SeparateChromosomes data=FaHetMoHom.linkage sizeLimit=56 lodLimit=4.3 informativeMask=1 >map1.txt
    
    ***
    LOD(16, 0) = 4.350864189212862
    LOD(15, 0) = 4.0594197333830895
    LOD(15, 1) = 2.699498039411941
    LOD(14, 2) = 1.20801156790841
    LOD(16, 0) = 4.350864189212862
    LOD(15, 0) = 4.0594197333830895
    LOD(15, 1) = 2.699498039411941
    LOD(14, 2) = 1.20801156790841
    Family family
    Number of different markers = 352
    4.3
    number of LGs = 150 singles = 4628
    Removing LG 26 (as too small) with size 54
    Removing LG 27 (as too small) with size 54
    Removing LG 28 (as too small) with size 53
    Removing LG 29 (as too small) with size 52
    Removing LG 30 (as too small) with size 51
    .
    .
    .
    
    Number of LGs = 25, markers in LGs = 2371, singles = 2557
    

    5) JoinSingles

    java -cp /data/programs/lepmap2/bin JoinSingles map1.txt data=FaHetMoHom.linkage lodLimit=3 lodDifference=1 >map1_js.txt
    ***
    Mendel error statistics:
    0->0 : 0
    0->1 : 0
    0->2 : 0
           Error rate = 0.0
    1->0 : 0
    1->1 : 0
    1->2 : 0
           Error rate = 0.0
    2->0 : 0
    2->1 : 0
    2->2 : 0
           Error rate = 0.0
    0,2->0,2 : 77323
      0,2->1 : 143
    1,2->1,2 : 0
      1,2->0 : 0
           Error rate = 0.0018459711357240597
    Warning: there are Mendel errors
    ***
    Filtering markers based on segregation distortion
    Removed 0 markers from family family
    Maternally informative markers = 0 (of 4928)
    Paternally informative markers = 4928
    Maternally or paternally informative markers = 4928
    ***
    LOD(16, 0) = 4.350864189212862
    LOD(15, 0) = 4.0594197333830895
    LOD(15, 1) = 2.699498039411941
    LOD(14, 2) = 1.20801156790841
    LOD(16, 0) = 4.350864189212862
    LOD(15, 0) = 4.0594197333830895
    LOD(15, 1) = 2.699498039411941
    LOD(14, 2) = 1.20801156790841
    Family family
    Number of different markers = 352
    4.0594197333830895 vs. 2.412252429474032
    4.0594197333830895 vs. 2.412252429474032
    4.0594197333830895 vs. 2.412252429474032
    4.0594197333830895 vs. 2.412252429474032
    4.0594197333830895 vs. 2.412252429474032
    4.0594197333830895 vs. 0.0
    4.0594197333830895 vs. 0.0
    3.476807474383648 vs. 0.0
    1977 : chr14 : 3.1856403883267372 vs. chr15 : 3.1856403883267372 (not joined)
    3.7680673719722346 vs. 2.125076191034331
    3.1856403883267372 vs. 0.0
    3.476807474383648 vs. 0.0
    3.1856403883267372 vs. 0.0
    3.7680673719722346 vs. 0.0
    4.0594197333830895 vs. 0.0
    3866 : chr1 : 3.1856403883267372 vs. chr11 : 3.1856403883267372 (not joined)
    3.1856403883267372 vs. 1.5509305371562556
    4.0594197333830895 vs. 2.412252429474032
    3.476807474383648 vs. 1.8379690035632463
    4.0594197333830895 vs. 2.412252429474032
    Number of joined markers in chr 1 is 0
    Number of joined markers in chr 2 is 1
    Number of joined markers in chr 3 is 4
    Number of joined markers in chr 4 is 0
    Number of joined markers in chr 5 is 0
    Number of joined markers in chr 6 is 1
    Number of joined markers in chr 7 is 1
    Number of joined markers in chr 8 is 1
    Number of joined markers in chr 9 is 0
    Number of joined markers in chr 10 is 1
    Number of joined markers in chr 11 is 3
    Number of joined markers in chr 12 is 3
    Number of joined markers in chr 13 is 1
    Number of joined markers in chr 14 is 0
    Number of joined markers in chr 15 is 0
    Number of joined markers in chr 16 is 0
    Number of joined markers in chr 17 is 0
    Number of joined markers in chr 18 is 0
    Number of joined markers in chr 19 is 0
    Number of joined markers in chr 20 is 0
    Number of joined markers in chr 21 is 1
    Number of joined markers in chr 22 is 0
    Number of joined markers in chr 23 is 0
    Number of joined markers in chr 24 is 0
    Number of joined markers in chr 25 is 1
    joined 18 single markers, non-conflicting LOD score > 3.1856403883267372
    Number of LGs = 25, markers in LGs = 2391, singles = 2537
    

    6) OrderMarkers

    java -cp /data/programs/lepmap2/bin/ OrderMarkers map=map1_js.txt data=FaHetMoHom.f.linkage chromosome=2 initRecombination=0.05 0 >order1.txt
    ***
    Mendel error statistics:
    0->0 : 0
    0->1 : 0
    0->2 : 0
           Error rate = 0.0
    1->0 : 0
    1->1 : 0
    1->2 : 0
           Error rate = 0.0
    2->0 : 0
    2->1 : 0
    2->2 : 0
           Error rate = 0.0
    0,2->0,2 : 77161
      0,2->1 : 129
    1,2->1,2 : 0
      1,2->0 : 0
           Error rate = 0.0016690386854703067
    Warning: there are Mendel errors
    ***
    Filtering markers based on segregation distortion
    Removed 0 markers from family family
    Maternally informative markers = 0 (of 4928)
    Paternally informative markers = 4831
    Maternally or paternally informative markers = 4831
    ***
    Removed 0 markers
    Number of LGs = 25
    163->1
    1->1
    Initial score = 0.0
    Iteration 1 of 6
    Polishing map...
    score = 0.0
    Iteration 2 of 6
    Polishing map...
    score = 0.0
    Iteration 3 of 6
    Polishing map...
    score = 0.0
    Iteration 4 of 6
    Polishing map...
    score = 0.0
    Iteration 5 of 6
    Polishing map...
    score = 0.0
    Iteration 6 of 6
    Polishing map...
    score = 0.0
    Final score = 0.0
    

    Regards.
    R

     
  • Pasi Rastas

    Pasi Rastas - 2017-04-18

    Dear R Sheldon,

    Thank you for your detailed question.

    My guess is that all marker are identical, that is why you get all markers collapsing into one. Does this happen on all linkage groups or only on (chromosome=) 2? By adding parameter outputPhasedData=1 LM will ouput the most likely segregation patterns. These can provide more information.

    With only 16 individuals, the linkage mapping does not necessary work that simply from the paternal markers. Based on the output of SeparateChromosomes and JoinSingles, you are throwing away too many linkage groups and markers with sizeLimit=56. (sizeLimit could be omitted or be set to about 3-4, this will yield much more groups).

    I would try to get the chromosomes from the maternal markers. As there is no recombination, you should find 16 groups easily. These can be used, e.g. to verify your paternal linkage groups. If you have a mapping to a genome, it is quite easy to link paternal and maternal linkage groups (by eyeballing or maybe even using ScaffoldHMM)
    Anyway, you probably need some manual work to finish your maps.

    Cheers,
    Pasi

     

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