SUMMARY-Linkage problem(long)
Lucien Bachner
bachner at Cassini.genethon.fr
Wed Dec 21 05:44:06 EST 1994
Hello
As the problem I have has received very interesting answers
I post them to the list.
Several persons have asked for my pedfile and datafile,
they are at the end of this message.
I had no time yet to test the proposed solutions
because I'm overLODed (despite my poor English it's not a typo or misspelling).
I will post the result as soon as I get one
and also other answers if they are some more.
Thank you to
Iain fenton WMGIF at CARDIFF.AC.UK
Alex Schaffer schaffer at cs.rice.edu
Sabine Faure faure at halogene.genethon.fr
Jonathan Haines HAINES at HELIX.MGH.HARVARD.EDU
Gerard Tromp tromp at sanger.bcm.tju.edu
MERRY CHRISTMAS AND HAPPY NEW YEAR
Lucien Bachner
_____________________________________________________________________
ORIGINAL QUESTION WAS :
I have a strange mlink problem.
The analysis is a dominant disease in a seven generations pedigree
with 171 individuals and one loop.
All files have been checked and look correct.
The results are always -infinity for all thetas,
for any pair of loci (marker-marker or disease-marker).
I have tried classical mlink, and fast and slow versions of
Fastlink/mlink, all on a Sun ipx, and always the same results.
I have also changed "scale" from 2 to 10 in mldefs.h in Fastlink,no differences.
I have tried two versions of unknown, no differences.
I have no error messages or warnings from any program.
I have no more ideas so if you can help me please do it.
Thank you in advance
=====================================================
| Lucien Bachner |
| Laboratoire de Biochimie Genetique,Hopital Cochin.|
| 123 Bd. Port Royal, 75014 Paris, France. |
| Tel: (33 1) 42-34-12-12 ext 3039 |
| FAX: (33 1) 44-41-15-22 |
| e-mail : bachner at Cassini.genethon.fr |
| bachner at citi2.fr |
=====================================================
_______________________________________________________________________
i would guess that something is wrong in the DATAFILE, particularly if
UNKNOWN is happy, that would suggest that the PEDFILE is ok. if it is only
one family, albeit an *enormous* family :-) can you post the PEDFILE &
DATAFILE to this list so that we can play with them ? you could think of
it as an early christmas present to us !!
Iain Fenton, Cardiff, UK.
_________________________________________________________________________
Bonjour,
Il m'est arrive d'avoir ce probleme et ce pour 2 raisons differentes:
- incompatibilite (ce qui ici ne semble poas le cas)
- frequence allelique a 0 et non 0.000001
Bon courage,
Sabine FAURE.
__________________________________________________________________________
If your mlink problem is not yet solved, you might try the following:
1). scale may be less important than scalemult. You might try changing
both.
2). In a large pedigree like yours (and I am assuming there are lots of
missing individuals at the top of the pedigree), especially with a loop,
there could be "hidden" inconsistencies that unknown will not pick up. This
would arise if inferred genotypes migrate more than one generation upwards
and then become inconsistent (e.g. inferred genotypes for 4 deceased siblings
indicate 5 chromosomes for 1 set of parents). We had this problem in an
8 generation Alzheimer's pedigree and it took us a very long time to
figure out where the problem was.
Jonathan
________________________________________________________________________________
Hello Lucien,
I second Iain Fenton's suggestion about posting/mailing the ped & data
files. Will be happy to play with it. I have had similar experiences with too
many loops in the pedigree. It was a subtle problem, but also gave "inconsistent"
results even though unknown was happy, and by eye the data looked consistent. It
took considerable effort to sort that one out. Have you tried analysing sub-parts
of the pedigree ? That's one of my first approaches to check the consistency --
at least it tells one when additional information added to "working" parts messes
up the analysis.
Anyway, if you post/mail the ped and dat files will be glad to have a
look.
Gerard
__________________________________________________________________________________
Lucien,
I have recently discovered that when the pedigree has at least one loop,
unknown does very little to detect incompatibilities. It is likely that
you have an incompatibility that is not detected. You may be able to
remove the loop and see if unknown will detect the incompatibility.
We are currently in the process of doing a serious revision to
unknown for various reasons, this being one of them.
If you wish to send me pedin.dat, datain.dat, script, etc. as specified
in README.bugreport, I can investigate further.
Regards,
Alejandro
_______________________________________________________________________________________
LOOP IS AT PERSONS 159 and 160, I broke it at 160
1 3 137 138 2 2 2 1 2 1 2 1 2 1 3
1 75 126 3 1 2 2 1 3 1 3 1 3 2 3
1 2 126 3 1 2 2 1 4 1 4 2 4 2 3
1 1 126 3 2 2 2 2 3 1 4 2 4 2 3
1 120 126 3 1 2 2 1 4 2 3 1 3 2 4
1 6 126 3 2 2 2 2 4 2 4 1 4 1 4
1 104 126 3 2 2 2 2 4 2 3 1 3 2 4
1 16 126 3 2 2 2 1 3 2 3 1 3 1 4
1 21 126 3 1 2 2 2 3 1 3 2 3 1 4
1 17 126 3 2 1 2 2 4 1 4 2 4 1 4
1 55 75 127 1 1 2 1 9 1 1 1 4 3 3
1 95 75 127 2 1 2 1 5 1 3 3 4 3 5
1 5 2 128 1 2 2 1 9 1 4 4 5 3 6
1 4 2 128 1 1 1 1 9 1 2 2 5 2 13
1 122 129 1 2 2 2 1 3 1 3 2 4 2 7
1 58 129 1 2 1 2 1 3 1 5 2 3 2 6
1 59 129 1 1 2 2 2 3 1 5 2 3 3 7
1 56 129 1 1 2 2 1 2 4 5 3 4 3 6
1 121 120 130 1 2 2 4 12 3 6 1 3 4 8
1 119 120 130 2 2 2 1 2 0 0 0 0 4 8
1 118 120 130 1 2 2 1 2 3 6 1 3 4 8
1 57 139 140 1 1 2 2 4 2 2 1 3 2 8
1 9 131 6 2 1 1 1 2 4 6 2 4 4 9
1 10 131 6 1 2 2 1 2 4 6 2 4 4 9
1 8 131 6 2 2 2 4 4 2 6 1 2 1 9
1 7 131 6 1 2 2 1 2 2 5 1 4 4 4
1 107 132 104 2 2 2 2 8 2 6 1 7 1 2
1 105 132 104 1 2 2 3 4 3 6 3 7 1 4
1 106 136 104 1 1 1 2 7 2 6 1 3 2 8
1 14 133 16 1 2 2 1 4 3 5 1 3 1 13
1 15 133 16 1 2 2 1 4 2 5 1 1 1 13
1 35 133 16 2 2 2 1 1 2 3 1 4 4 13
1 20 21 134 1 1 1 3 8 1 7 2 4 4 10
1 19 21 134 1 1 1 2 6 1 1 2 4 1 10
1 87 21 134 1 1 1 2 6 1 1 2 4 4 10
1 18 135 17 2 1 1 4 5 1 5 2 3 1 11
1 123 125 122 2 1 1 3 8 1 1 2 4 7 9
1 117 125 122 2 1 1 3 7 1 2 2 5 2 7
1 139 126 3 1 1 2 0 0 0 0 0 0 0 0
1 62 137 138 2 2 2 1 10 1 2 2 4 1 12
1 49 137 138 2 1 2 4 10 2 3 1 3 1 2
1 12 137 138 2 2 2 1 10 1 2 1 2 1 12
1 11 137 138 1 1 2 1 10 1 2 1 2 1 2
1 66 137 138 1 1 2 4 10 1 2 2 4 1 12
1 80 137 138 2 2 2 4 10 1 2 2 4 1 2
1 61 141 62 1 2 2 4 10 1 6 1 2 11 12
1 65 141 62 1 1 2 3 10 1 6 1 2 11 12
1 91 141 62 2 1 2 3 10 2 5 2 4 1 11
1 60 141 62 2 1 2 3 10 2 5 2 4 1 11
1 53 155 12 2 2 2 1 10 1 5 2 3 1 12
1 99 155 12 2 1 2 1 10 2 3 1 3 9 12
1 88 11 156 2 1 2 1 2 1 6 2 5 1 7
1 67 11 156 2 1 2 1 2 2 6 1 5 2 7
1 68 61 142 2 1 2 1 4 1 6 2 5 9 12
1 70 61 142 1 1 2 1 10 1 6 1 5 9 12
1 69 61 142 1 1 2 1 10 1 6 1 5 9 11
1 63 61 142 2 2 2 3 4 1 3 2 4 7 12
1 64 61 142 1 1 1 3 4 3 6 1 4 9 12
1 90 143 91 2 1 1 10 12 3 5 2 4 3 11
1 54 157 53 2 1 1 1 10 3 5 2 6 1 2
1 50 157 53 2 1 1 10 10 2 5 2 2 1 2
1 52 157 53 2 1 1 1 3 3 5 2 6 1 7
1 51 157 53 2 1 1 0 0 0 0 0 0 0 0
1 100 158 99 1 1 1 1 4 1 3 0 0 5 9
1 13 137 138 1 2 2 2 4 2 3 3 4 1 12
1 101 13 144 2 1 2 1 2 3 5 2 3 1 1
1 113 13 144 2 2 2 1 4 3 5 2 3 1 12
1 31 13 144 2 1 2 2 3 1 3 3 4 1 12
1 36 13 144 2 1 2 3 4 2 5 2 4 1 12
1 40 13 144 2 2 2 2 3 2 5 2 4 9 12
1 83 13 144 2 2 2 1 4 2 5 2 4 1 9
1 32 13 144 1 1 2 1 2 1 3 3 4 1 9
1 71 13 144 2 2 2 1 4 3 5 2 3 1 12
1 108 13 144 2 2 2 2 3 1 3 3 4 1 1
1 44 13 144 2 2 2 2 3 2 5 2 4 9 12
1 102 145 101 2 1 1 1 4 1 3 2 3 1 6
1 103 145 101 2 1 1 1 4 4 5 2 3 1 1
1 110 146 113 2 2 2 4 12 5 6 2 3 12 15
1 114 146 113 1 1 1 2 4 3 5 2 5 12 15
1 115 146 113 2 1 1 1 12 3 6 3 5 1 1
1 28 147 31 2 1 1 3 4 3 6 3 5 1 16
1 29 147 31 2 1 1 2 3 1 6 4 5 12 13
1 30 147 31 2 1 1 2 3 3 4 2 3 12 16
1 27 147 31 2 1 1 3 3 3 4 2 3 12 16
1 37 148 36 2 1 1 4 12 2 6 3 4 1 12
1 38 148 36 2 1 1 3 4 2 6 3 4 12 12
1 41 149 40 1 1 1 3 11 1 5 2 7 12 16
1 42 149 40 1 1 1 3 11 3 5 2 5 9 16
1 39 149 40 1 2 2 2 11 1 5 2 7 3 9
1 81 150 83 2 1 1 4 5 1 5 2 4 1 6
1 82 150 83 1 1 1 1 8 5 6 2 3 1 15
1 33 32 151 2 1 1 2 6 1 3 4 4 8 9
1 34 32 151 1 1 1 1 6 3 3 3 4 8 9
1 73 152 71 2 1 1 4 4 1 3 3 3 1 10
1 74 152 71 1 1 1 1 4 1 5 2 3 10 12
1 72 152 71 2 1 1 4 4 5 6 1 2 1 11
1 109 153 108 2 1 1 3 3 3 5 4 4 1 13
1 111 153 108 1 1 1 2 3 3 3 3 4 1 11
1 112 153 108 2 1 1 2 4 1 3 4 4 1 11
1 46 154 44 2 1 1 2 3 2 3 3 4 0 0
1 47 154 44 2 2 2 2 3 3 5 2 3 10 12
1 78 159 160 2 1 2 1 7 1 6 1 4 1 12
1 23 159 160 1 1 2 3 7 3 6 2 4 1 5
1 22 159 160 2 1 2 3 4 3 6 2 4 8 12
1 26 159 160 1 1 2 3 4 1 6 1 4 1 12
1 45 161 162 2 1 2 1 5 3 6 1 3 1 14
1 48 161 162 2 1 2 1 1 3 6 1 1 1 14
1 43 161 162 2 2 2 1 5 3 6 1 2 4 8
1 24 163 164 1 1 2 1 3 3 4 1 5 5 9
1 25 163 164 1 1 2 3 4 3 3 1 5 9 14
1 116 76 78 1 2 2 1 8 1 6 1 3 8 12
1 86 76 78 2 1 2 3 7 1 6 1 3 12 12
1 96 76 78 2 2 2 1 3 3 6 1 5 12 12
1 89 76 78 2 1 2 1 8 1 6 3 4 1 8
1 79 165 86 1 1 1 1 7 6 7 1 3 12 15
1 85 165 86 2 1 1 1 3 6 7 1 3 12 15
1 84 165 86 2 1 1 1 7 1 1 3 4 12 15
1 98 166 96 2 2 2 1 8 3 7 4 5 12 15
1 97 166 96 1 1 1 1 8 3 3 4 5 12 15
1 92 167 89 1 1 1 1 3 1 1 3 6 7 8
1 93 167 89 1 1 1 1 3 1 1 3 6 2 8
1 94 167 89 1 1 1 3 8 1 1 3 6 7 8
1 138 168 169 2 0 2 0 0 0 0 0 0 0 0
1 160 168 169 2 0 2 0 0 0 0 0 0 0 0
1 161 168 169 1 2 2 0 0 0 0 0 0 0 0
1 164 168 169 2 2 2 0 0 0 0 0 0 0 0
1 126 0 0 1 1 2 3 4 3 4 3 4 3 4
1 127 0 0 2 1 2 5 9 0 0 0 0 3 5
1 128 0 0 2 1 2 0 0 0 0 0 0 6 13
1 129 0 0 1 1 2 0 0 3 5 3 4 6 7
1 130 0 0 2 1 2 2 12 0 0 0 0 0 0
1 140 0 0 2 1 2 0 0 0 0 0 0 0 0
1 131 0 0 1 1 2 1 4 5 6 2 4 4 9
1 132 0 0 1 1 2 3 8 4 8 0 0 0 0
1 136 0 0 1 1 2 0 0 0 0 0 0 0 0
1 133 0 0 1 1 2 1 4 0 0 1 4 0 0
1 134 0 0 2 1 2 6 8 1 7 0 0 0 0
1 135 0 0 1 1 2 0 0 0 0 0 0 0 0
1 125 0 0 1 1 2 7 8 1 2 2 5 0 0
1 141 0 0 1 1 2 3 4 5 6 0 0 0 0
1 155 0 0 1 1 2 0 0 3 5 0 0 0 0
1 156 0 0 2 1 2 0 0 0 0 0 0 0 0
1 142 0 0 2 1 2 1 3 0 0 4 5 7 9
1 143 0 0 1 1 2 0 0 0 0 0 0 0 0
1 157 0 0 1 1 2 0 0 2 3 2 6 2 7
1 158 0 0 1 1 2 0 0 0 0 0 0 0 0
1 144 0 0 2 1 2 1 3 1 5 0 0 1 9
1 145 0 0 1 1 2 0 0 1 4 0 0 1 6
1 146 0 0 1 1 2 2 12 5 6 0 0 1 15
1 147 0 0 1 1 2 3 4 4 6 2 5 13 16
1 148 0 0 1 1 2 0 0 0 0 0 0 0 0
1 149 0 0 1 1 2 0 0 1 3 5 7 3 16
1 150 0 0 1 1 2 5 8 1 6 0 0 6 15
1 151 0 0 2 1 2 0 0 0 0 0 0 0 0
1 152 0 0 1 1 2 2 4 1 6 1 3 10 11
1 153 0 0 1 1 2 3 4 3 5 0 0 11 13
1 154 0 0 1 1 2 0 0 0 0 3 4 0 0
1 76 0 0 1 1 2 3 8 0 0 3 5 8 12
1 165 0 0 1 1 2 0 0 0 0 0 0 0 0
1 166 0 0 1 1 2 0 0 0 0 0 0 0 0
1 167 0 0 1 1 2 0 0 0 0 0 0 2 7
1 137 0 0 1 0 2 0 0 0 0 0 0 0 0
1 159 171 170 1 0 2 0 0 0 0 0 0 0 0
1 162 0 0 2 0 2 0 0 0 0 0 0 0 0
1 163 0 0 1 0 2 0 0 0 0 0 0 0 0
1 168 172 173 1 0 2 0 0 0 0 0 0 0 0
1 169 0 0 2 0 2 0 0 0 0 0 0 0 0
1 170 172 173 2 0 2 0 0 0 0 0 0 0 0
1 171 0 0 1 0 2 0 0 0 0 0 0 0 0
1 172 0 0 1 0 2 0 0 0 0 0 0 0 0
1 173 0 0 2 0 2 0 0 0 0 0 0 0 0
_________________________________________________________________________
5 0 0 5 << NO. OF LOCI, RISK LOCUS, SEXLINKED (IF 1) PROGRAM
0 0.0 0.0 0 << MUT LOCUS, MUT RATE, HAPLOTYPE FREQUENCIES (IF 1)
1 2 3 4 5
1 2 << AFFECTION, NO. OF ALLELES
0.999500 0.000500 << GENE FREQUENCIES
2 << NO. OF LIABILITY CLASSES
0.0000 0.8 0.8
0.0000 1.0 1.0 << PENETRANCES
3 12 << ALLELE NUMBERS, NO. OF ALLELES
0.083 0.083 0.083 0.083 0.083 0.083 0.083 0.083 0.083 0.083 0.083 0.087 << GENE FREQUENCIES
3 8 << ALLELE NUMBERS, NO. OF ALLELES
0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125 << GENE FREQUENCIES
3 8 << ALLELE NUMBERS, NO. OF ALLELES
0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125 << GENE FREQUENCIES
3 16 << ALLELE NUMBERS, NO. OF ALLELES
0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 0.0625 << GENE FREQUENCIES
0 0 << SEX DIFFERENCE, INTERFERENCE (IF 1 OR 2)
0.10000 0.1 0.1 0.1 << RECOMBINATION VALUES
1 0.10000 0.45000 << REC VARIED, INCREMENT, FINISHING VALUE
_______________________________________________________________________________
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