Episodic Ataxia (EA) pedigree: NPL
Results of the Non-Parametric Linkage (NPL) Analysis from SimWalk2 2.91
In the table below, at each marker locus, are the results for five statistics.
These statistics measure the degree of clustering, among the affecteds, of the
founder-alleles, i.e., the marker alleles descending from the founders.
Specifically, at each marker:
The BLOCKS statistic is the number of founder-alleles contributing alleles
to the affecteds. This statistic was designed for traits best modeled
by RECESSIVE inheritance. (This statistic was formerly known as STAT A.)
The MAX-TREE statistic is the largest number of affecteds inheriting an allele
from one founder-allele. This statistic was designed for traits best modeled
by DOMINANT inheritance. (This statistic was formerly known as STAT B.)
The ENTROPY statistic is a measure of the entropy of the alleles among the
affecteds. (This statistic was formerly known as STAT C.)
The NPL_PAIR statistic is roughly the sum of conditional kinship coefficients
for all affected pairs. This statistic was designed for traits best modeled
by ADDITIVE inheritance. (This statistic was formerly known as STAT D.)
The NPL_ALL statistic is a measure of whether a few founder-alleles are overly
represented in affecteds. This statistic was designed for traits best modeled
by ADDITIVE inheritance. (This statistic was formerly known as STAT E.)
More information on these statistics can be found in Lange and Lange (2004),
Sobel and Lange (1996) American Jounal of Human Genetics 58:1323-1337, and
Whittemore and Halpern (1994) Biometrics 50:118-127.
In the table below, at each marker locus, the first value listed is the
empirical p-value for each statistic, i.e., the probability of obtaining a
value for that statistic equal to, or more extreme than, the observed value,
if the trait were in fact unlinked to the markers. Thus, p-values closer to
0.0 indicate higher significance. Currently, the minimum p-value is 0.0001
[to lower this minimum, increase batch item #48: min = 1 / batch-item-#48].
A p-value of 0.5 indicates equal evidence for and against linkage. As usual,
the maximum p-value is 1.0.
Next, the -log10(p-value) is listed. Here, the larger the value, the more
significant. These values have a minimum of 0.0, and a maximum of 4.0000
[to raise this maximum, increase batch item #48: max = log10(batch-item-#48)].
A value of 0.3010 [from: -log10(0.5)] indicates equal evidence for and against
linkage.
BLOCKS MAX-TREE ENTROPY NPL_PAIR NPL_ALL
RECESSIVE DOMINANT STATISTIC ADDITIVE ADDITIVE
~~~~~~~~~ ~~~~~~~~~ ~~~~~~~~~ ~~~~~~~~~ ~~~~~~~~
RUN PED PEDIGREE MARKER P-VALUE P-VALUE P-VALUE P-VALUE P-VALUE
NUM NUM NAME NAME -Log(P) -Log(P) -Log(P) -Log(P) -Log(P)
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33 ALL PEDIGREES S91 0.7917 0.0008 0.0188 0.0008 0.0008
0.1014 3.1211 1.7266 3.1086 3.1240
33 ALL PEDIGREES S100 0.8040 0.0007 0.0186 0.0007 0.0007
0.0947 3.1400 1.7304 3.1424 3.1485
33 ALL PEDIGREES CACNL1A1 0.8079 0.0018 0.0226 0.0019 0.0016
0.0927 2.7512 1.6451 2.7257 2.8005
33 ALL PEDIGREES S372 0.5764 0.0047 0.0235 0.0042 0.0025
0.2393 2.3244 1.6288 2.3817 2.6072
33 ALL PEDIGREES pY2/1 0.3926 0.0086 0.0265 0.0076 0.0042
0.4060 2.0655 1.5773 2.1169 2.3752
33 ALL PEDIGREES pY21/1 0.3831 0.0080 0.0253 0.0073 0.0042
0.4167 2.0969 1.5969 2.1367 2.3768
33 ALL PEDIGREES KCNA5 0.3807 0.0081 0.0247 0.0079 0.0044
0.4194 2.0915 1.6073 2.1024 2.3565
33 ALL PEDIGREES S99 0.3805 0.0078 0.0235 0.0079 0.0040
0.4196 2.1079 1.6289 2.1024 2.3979
33 ALL PEDIGREES S93 0.3871 0.0178 0.0375 0.0185 0.0115
0.4122 1.7495 1.4258 1.7320 1.9400
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The comma-delimited table below is to facilitate graphing the above results.
These overall results derive from ALL pedigrees. ##
The table below lists for each marker, the distance from the first marker
in sex-average Haldane cM and then the -log10(p-value) for each statistic.
For these p-value derived terms: the larger the value, the more significant.
For example, for some data, a value above 2.00 might be considered significant.
Each position that includes a result above 2.00 is flagged with '##'.
These values have a minimum of 0.0, and a maximum of 4.0000
[to raise this maximum, increase batch item #48: max = log10(batch-item-#48)].
A value of 0.3010 [from: -log10(0.5)] indicates equal evidence for and against
linkage.
MARKER , POSITION , -LOG10(p-values)
NAME , in Haldane cM , BLOCKS , MAX-TREE, ENTROPY , NPL_PAIR, NPL_ALL
S91 , 0.0000 , 0.101 , 3.121 , 1.727 , 3.109 , 3.124 ##
S100 , 1.0101 , 0.095 , 3.140 , 1.730 , 3.142 , 3.148 ##
CACNL1A1 , 2.0203 , 0.093 , 2.751 , 1.645 , 2.726 , 2.801 ##
S372 , 5.1140 , 0.239 , 2.324 , 1.629 , 2.382 , 2.607 ##
pY2/1 , 8.2078 , 0.406 , 2.066 , 1.577 , 2.117 , 2.375 ##
pY21/1 , 9.2179 , 0.417 , 2.097 , 1.597 , 2.137 , 2.377 ##
KCNA5 , 10.2281 , 0.419 , 2.092 , 1.607 , 2.102 , 2.357 ##
S99 , 11.2382 , 0.420 , 2.108 , 1.629 , 2.102 , 2.398 ##
S93 , 12.2484 , 0.412 , 1.749 , 1.426 , 1.732 , 1.940
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Episodic Ataxia (EA) pedigree: NPL
Recombination Statistics from SimWalk2 2.91
Here, for each marker interval, is the number of recombinations observed
and the number expected, given the total number of meioses & the interval size.
The 'observed value' listed below is the average over all pedigrees that were
sampled during the MCMC phase. Thus, this value is an estimate of the average
over all possible configurations each weighted by its likelihood, i.e.,
given the data, this is our best estimate of the true value.
We also estimate the p-value for these observations, i.e., the probability that
one would observe this many recombination events OR MORE within this interval,
again given the total number of meioses & the interval size. A very small
p-value indicates that the number of observed recombinations would be more
consistent with a larger recombination distance for this marker interval.
Similarly, a p-value close to 1 indicates that the user-specified recombination
distance for this interval should be re-evaluated and perhaps made smaller.
Such extreme p-values are flagged when they appear.
The total number of pedigrees actually analyzed here: 1
The total number of meioses contained in these pedigrees: 40
Since the user-specified recombination distances are sex-independent,
we report the combined female and male recombination statistics.
OVERALL RECOMBINATION STATISTICS
POSITION MARKER RECOMB. RECOMBINATION EVENTS SIGNIFICANCE INTERVAL
Haldane cM NAME FRACTION OBSERVED & EXPECTED (P-VALUE) NUMBER
0.000 S91
0.01000 0.225 0.400 0.83532 1
1.010 S100
0.01000 0.203 0.400 0.85190 2
2.020 CACNL1A1
0.03000 1.014 1.200 0.69886 3
5.114 S372
0.03000 2.727 1.200 0.16172 4
8.208 pY2/1
0.01000 0.320 0.400 0.76368 5
9.218 pY21/1
0.01000 1.078 0.400 0.29520 6
10.228 KCNA5
0.01000 0.087 0.400 0.93812 7
11.238 S99
0.01000 0.373 0.400 0.72406 8
12.248 S93
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Episodic Ataxia (EA) pedigree: NPL
Batch Instruction Parameters
Below are listed the SimWalk2 2.91 instruction parameters used in this run.
Also, where appropriate, the default values of the batch items are listed.
(Please see the documentation for a more complete description
of the meaning of these parameters.)
Batch Actual
Item GENERAL PARAMETERS Value
# 1 Type of analysis: NON-PARAMETRIC
# 2 Integer label attached to the output files: 33
# 3 Title for this run is the above title: (see above)
# 4 Continuation of previous run? NO
Number of pedigrees analyzed in this entire run: 1
Batch Actual
Item INPUT-FILE PARAMETERS Value
#09 Map data filename: MAP.DAT
#10 Locus data filename: LOCUS.DAT
#11 Pedigree data filename: PEDIGREE.DAT
#12.1 Symbol for females (case insensitive): F
#12.2 Symbol for males (case insensitive): M
#13.1 Trait locus included in analyzed data? YES
#16 Affection status is indicated by the label: 2
#17 Affection status is indicated at the: TRAIT LOCUS
#18 Number of quantitative variables: 1
#19 No trait penetrances file:
Marker Map:
POSITION (Haldane cM) MARKER RECOMBINATION RATES INTERVAL
FEMALE & MALE ORDER FEMALE & MALE NUMBER
0.000 0.000 S91
0.01000 0.01000 1
1.010 1.010 S100
0.01000 0.01000 2
2.020 2.020 CACNL1A1
0.03000 0.03000 3
5.114 5.114 S372
0.03000 0.03000 4
8.208 8.208 pY2/1
0.01000 0.01000 5
9.218 9.218 pY21/1
0.01000 0.01000 6
10.228 10.228 KCNA5
0.01000 0.01000 7
11.238 11.238 S99
0.01000 0.01000 8
12.248 12.248 S93
Batch Default Actual
Item RUN-SPECIFYING PARAMETERS Value Value
#20 Number of pedigrees sampled for each input pedigree 1000 1000
#21 Number of parallel runs during simulated annealing: 1 1
#22 Initial temperature value: 100.00 100.00
#23 Temperature change factor: 0.99 0.99
#24 Number of temperature changes: 800 800
#25 Number of pre-simulated annealing steps: 0 0
#26 Maximum number of attempts to initialize pedigrees: 64 64
Number of steps per temperature is roughly: 5200
#29.1 using a minimum number of steps of: 1000 1000
#30.1 and a multiplicative factor of: 10 10
Number of steps per sampled pedigree is roughly: 5200
#29.2 using a minimum number of steps of: 1000 1000
#30.2 and a multiplicative factor of: 10 10
Mean number of transitions per step
#31.1 during simulated annealing: 2.00 2.00
#31.2 during Markov chain Monte Carlo process: 2.00 2.00
Weight factor for individuals untyped at a locus
#32.1 during simulated annealing: 10 10
#32.2 during Markov chain Monte Carlo process: 10 10
Frequency that next pivot is forced to be nearby
#33.1 during simulated annealing: 0.50 0.50
#33.2 during Markov chain Monte Carlo process: 0.50 0.50
Frequency that a founder transition is of type 2
#34.1 during simulated annealing: 0.25 0.25
#34.2 during Markov chain Monte Carlo process: 0.25 0.25
#35 Number of steps between free runs: 0 0
#36.1 Random seed number 1: 27713 27713
#36.2 Random seed number 2: 2321 2321
#36.3 Random seed number 3: 18777 18777
#37.1 Error model for mistyping: uniform uniform
#37.2 Overall rate of mistyping: 0.025 0.025
Batch Actual
Item OUTPUT-FILE PARAMETERS Value
#39 Files to output from IBD analysis: IBD & KINSHIP
#40 Output the pedigrees individually in INPED-nn.mmm? NO
#41 Output the location scores per pedigree in SCORE-nn.mmm? NO
#42 Threshold for mistyping probability to be significant: 0.50
#43 Export haplotypes for drawing applications? NO
#44.1 Threshold haplotype count for RERUN-nn.PED entry: 0
#44.2 Threshold recombinant count for RERUN-nn.PED entry: 0
#45 Threshold fraction of steps for RERUN-nn.PED entry: 0.85
#46.1 Output haplotypes in vertical representations? NO
#46.2 Output haplotypes using founder-haplotype labels? NO
#46.3 Force allele choice when no allele information exists? NO
#47 Output the sampled peds in LINKAGE-format in MODEL-nn.*? NO
#48 Num. of unconditional simulations for empirical p-value: 10000
#49.1 Number of points analyzed within each marker interval: 0
#49.2 Size of uniform grid interval for analysis positions: 1.00
With the above parameters, the number of steps
per simulated annealing run is roughly: 4160000
per Markov chain Monte Carlo run is roughly: 5200000
All relevant 'Run-Specifying Parameters' are at their default values.
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