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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