Parsimony methods
| | | | | | | | | |
1. Simple parsimony
| | | | | | | | | |
HAPAR
|
Parsimony
|
HA
|
No
|
None
|
Overcomes limitations of HAPINFREX
|
May be susceptible to HWE departures
|
Practical limit, biallelic
|
PC/UNIX
|
[39]
|
| | | | |
Increasing sample size improves
accuracy
| | | | |
HAPINFERX
|
Clark's
|
HA
|
No
|
None
|
Intuitive method, fast
|
May fail to start
|
Practical limit,
biallelic/multiallelic
|
UNIX
|
[37]
|
| | | | |
Reduced number
of haplotypes
|
Sensitive to
data order
| | | |
| | | | |
No limit on
number of loci
|
Unstable and
erroneous
estimates
| | | |
2. Phylogeny
| | | | | | | | | |
BPPH
|
IP
|
HA
|
No
|
IP
|
Similar to HAPH
|
User interface
|
Practical limit, biallelic
|
MAC
|
[45]
|
| | | | |
Speed
| | | | |
DPPH
|
PP
|
HA
|
No
|
PP
|
Handles large datasets
|
Theoretical
|
Practical limit, biallelic
|
MAC
|
[40, 43]
|
| | | | |
Speed
|
Strict population assumptions
| | | |
GPPH
|
PP
|
HA
|
No
|
PP
|
Handles large datasets
|
Theoretical
|
Practical limit, biallelic
|
MAC/PC/UNIX
|
[40, 42]
|
| | | | |
Speed
|
Strict population assumptions
| | | |
HAPH
|
IP
|
HA/HF
|
Yes
|
HWE, IP
|
Predicts haplotype blocks
|
No probability for haplotype assignments
|
Max 500 loci, Practical limit biallelic
|
Web-based
|
[44]
|
| | | | |
Constructs
haplotypes within blocks
| | | | |
| | | | |
Identifies block
structure
| | | | |
| | | | |
Web-based
| | | | |
Likelihood methods
| | | | | | | | | |
1. Maximum likelihood
| | | | | | | | |
Arlequin v2.0
|
EM
|
HA/HF
|
No
|
HWE
|
Includes numerous population genetic analysis tools
|
EM issues
|
EM Practical Limits, biallelic/multiallelic
|
JRE on MAC/PC/UNIX
|
[89]
|
CHAPLIN
|
ECM
|
HF
|
Yes
|
HWE
|
Graphical interface
|
ECM algorithm needs to be compared with standard EM methods
|
Practical limits, biallelic/multiallelic
|
PC
|
[91]
|
| | | | |
Association tests
| | | | |
| | | | |
HWE assumption relaxed in case
sample
| | | | |
EH
|
EM
|
HF
|
No
|
HWE
|
Estimates haplotype frequency
|
EM issues
|
No Max, 3-4 practical max, biallelic/multiallelic
|
PC
|
[85, 104]
|
| | | | |
Compares case-control HF
under different assumptions
|
Must specify mode
of inheritance and
penetrance of disease
| | | |
EHPLUS
|
EM
|
HF
|
No
|
HWE
|
Improves EH,
more loci and
polymorphic
markers
|
Long run times
for permutation
calculations
|
Max 5 loci,
15 alleles in
analysis
|
PC/UNIX
|
[84]
|
| | | | |
Incorporates
model-free
analysis
| | | | |
EM-DeCODER
|
EM
|
HA/HF
|
No
|
HWE
|
Program with
standard EM
algorithm
|
EM issues
|
Max 15 loci,
biallelic
|
UNIX
|
[57]
|
FASTEHPLUS
|
EM
|
HF
|
No
|
HWE
|
Similar to EHPLUS,
with speed
improvements
|
EM issues
|
Max 5 loci,
15 alleles in
analysis
|
PC/UNIX
|
[105]
|
GENECOUNTING
|
EM
|
HA/HF
|
Yes
|
HWE
|
Provides posterior
probabilities
for assigned
haplotypes
|
Missing data
limited to
biallelic loci
|
10-15 loci
practical
limit, biallelic/
multiallelic
|
PC/UNIX
|
[106]
|
| | | | |
Compares global
and specific
haplotypes
between groups
|
EM issues
| | | |
GCHAP
|
EM
|
HA/HF
|
YES
|
HWE
|
Haplotypes with
zero likelihood
dropped to
improve speed and
accuracy
|
EM issues
|
20 loci practical
limit, biallelic
|
JRE on
PC/UNIX
|
[107, 108]
|
| | | | |
Similar to SNPHAP
| | | | |
GS-EM
|
EM
|
HA/HF
|
Yes
|
HWE
|
Includes algorithm
for assigning probability to genotype
calls from several
genotyping
methods
|
EM issues
|
Practical limit,
biallelic
|
Web-based
|
[73]
|
| | | | |
Haplotypes constructed using assigned genotypes probability
|
Limited to biallelic SNPs
| | | |
| | | | |
Web-based
| | | | |
HAPZ
|
EH
|
HA/HF
|
Yes
|
HWE
|
Modified version of
SNPHAP that
accommodates
multiallelic loci
|
EM issues
|
Practical limit, biallelic/multiallelic
|
PC/UNIX
|
[106]
|
HAPMAX
|
MLE
|
HF
|
No
|
HWE
|
Ease of use
|
Accommodates a limited number
of SNPs
|
8 loci, biallelic
|
PC
|
[109]
|
| | | | | |
Interface
| | | |
HAPLOH
|
EM
|
HF
|
Yes
|
HWE
|
Handles some missing data
|
EM issues
|
10 loci, 40 alleles max, biallelic/multiallelic
|
UNIX
|
[47]
|
| | | | |
Utilises pedigree data, if available
| | | | |
| | | | |
Calculates standard
error
| | | | |
HAPLOSCOPE
|
EM/MCMC
|
†
|
†
|
†
|
Platform program, incorporates SNPHAP and PHASE v1.0
|
See individual programs for limitations/features
|
†
|
UNIX/Windows
|
[110]
|
| | | | |
Facilitates
comparison/testing
| | | | |
| | | | |
Graphical interface, identifies tagging SNPs and LD
blocks
| | | | |
HAPLOVIEW
|
EM+PL
|
HA/HF
|
Yes
|
HWE
|
Calculates pairwise LD
|
EM issues
|
100 s, practical limit, biallelic
|
JRE on MAC/PC/UNIX
|
[56]
|
| | | | |
Checks for
recombination
| | | | |
| | | | |
Identifies tagging
SNPs
| | | | |
| | | | |
Accepts pedigree
and unrelated
genotype data
| | | | |
HAPLO.STATS
|
EM
|
HA/HF
|
Yes
|
HWE
|
Incorporates
method similar to
SNPHAP, with user
inputs
|
Requires
knowledge of
S-Plus 6.0 or R
|
Practical
limit, biallelic/
multiallelic
|
S-PLUS
6.0 on
UNIX/R
on UNIX
& PC
|
[86]
|
| | | | |
Separate
programs that:
|
EM issues
| | | |
| | | | |
(1) assign
haplotypes with
posterior
probability of
assignments
| | | | |
| | | | |
(2) allow linear
regression for trait
to haplotype
analysis
| | | | |
| | | | |
(3) calculates score
statistic for haplotype phenotype
association
| | | | |
HIT
|
EM/MCMC/
MC+PL
|
†
|
†
|
†
|
Platform program,
incorporates
SNPHAP and
PHASE v1.0
|
See individual
programs for
limitations/
features
|
†
|
*
|
[111]
|
| | | | |
Facilitates
comparison
| | | | |
| | | | |
Graphical interface,
identifies
tagging SNPs
and LD blocks
| | | | |
HPLUS
|
EM+EE+PL
|
HA/HF
|
Yes
|
HWE
|
Provides posterior
probabilities for
assigned haplotypes
|
Requires Matlab
|
100 loci,
biallelic
|
MATLAB
on PC/
UNIX
|
[55, 83]
|
| | | | |
Compares
haplotype
frequencies
between groups,
adjusts for
covariates
|
EM issues
| | | |
| | | | |
Utilises pedigree
data, if available
| | | | |
LDSUPPORT
|
EM
|
HA/HF
|
Yes
|
HWE
|
Provides posterior
probabilities for
assigned haplotypes
|
EM issues
|
*
|
UNIX
|
[29, 112]
|
| | | | |
Identifies LD
blocks for
haplotype
reconstruction
| | | | |
| | | | |
Examines association with disease,
automation speeds
process
| | | | |
LOGINSERM
ESTIHAPLO
|
EM
|
HA/HF
|
Yes
|
HWE
|
Program uses ML
method to infer
haplotypes for individuals with missing
data
|
EM issues
|
Practical
limit, biallelic/multiallelic
|
PC/
UNIX
|
[80]
|
| | | | |
Offers option to
exclude individuals
with missing data
| | | | |
MLHAPFRE
|
EM
|
HF
|
Yes
|
HWE
|
Performance improves with presence of LD
|
Incorporated into Arlequin
|
16 loci, biallelic
|
JRE on Mac/PC/UNIX
|
[48]
|
| | | | |
Performs well with
large sample size
|
EM issues
| | | |
MLOCUS
|
EM
|
HA/HF
|
Yes
|
HWE
|
Provides posterior probabilities for assigned haplotypes
|
EM issues
|
11 loci, biallelic/multiallelic
|
PC
|
[46, 113]
|
| | | | |
Notes observed vs.
inferred haplotypes
| | | | |
| | | | |
Calculates pairwise LD
| | | | |
OSLEM
|
EM
|
Yes
|
No
|
HWE
|
Modified EM algorithm that runs 2 × faster
|
EM issues
|
Practical limit, biallelic
|
Web-based
|
[114]
|
PL-EM
|
EM+PL
|
HA/HF
|
Yes
|
HWE
|
Combines PL with EM
|
EM issues
|
100 s, practical limit, biallelic
|
PC/UNIX
|
[54]
|
| | | | |
EM-based version
of HAPLOTYPER
| | | | |
| | | | |
Calculates variance
of haplotype frequency estimates
| | | | |
SAS Genetics
|
EM
|
HA/HF
|
Yes
|
HWE
|
Provides posterior probabilities for assigned haplotypes
|
Requires SAS
|
Practical limit, biallelic/multiallelic
|
SAS on PC/UNIX
|
[115]
|
| | | | |
Incorporates
statistical tests and
procedures
|
EM issues
| | | |
SNPEM
|
EM
|
HF
|
No
|
HWE
|
Estimates
haplotype
frequency by
population
|
EM issues
|
10 loci, biallelic
|
UNIX
|
[10]
|
| | | | |
Compares global
and specific
haplotype between
2 groups
| | | | |
SNPHAP
|
EM
|
HA/HF
|
Yes
|
HWE
|
Uses posterior and
prior trimming to
handle large
number loci
|
EM issues
|
Practical limit,
biallelic
|
UNIX
|
[52]
|
| | | | |
Provides posterior
probabilities for
assigned haplotypes
| | | | |
THESIAS
|
S-EM
|
HF
|
Yes
|
HWE
|
Stochastic EM
avoids issues of
standard EM
programs
|
S-EM algorithm
needs to be
compared with
standard EM
methods
|
Practical limit,
20 loci,
biallelic
|
PC/UNIX
|
[53, 88]
|
| | | | |
Includes tests for
haplotype-phenotype association
| | | | |
| | | | |
Accommodates
large sample sizes
| | | | |
WHAP
|
EM
|
†
|
†
|
†
|
Uses haplotype
output from
SNPHAP for
association testing
|
EM issues
|
†
|
PC/UNIX
|
[116]
|
| | | | |
Allows weighted
association
analysis
|
Requires
separate
haplotyping
program
| | | |
Zaykin et al.
|
EM
|
HF
|
No
|
HWE
|
Program on
analysis of
haplotype-phenotype
association
|
EM issues
|
Practical
limit, biallelic/multiallelic
|
PC/UNIX
|
[82]
|
| | | | | |
Subjects with
missing data
ignored
| | | |
Zou and Zhao
|
MLE/EM
|
HF
|
Yes
|
HWE
|
Adjust haplotype
frequency estimates for genotyping error
|
Assumes genotyping errors are
random
|
Practical limits,
biallelic/multiallelic
|
*
|
[68]
|
| | | | |
Program also
works for nuclear
families
|
Assumes error
rates are known
| | | |
3locus.PAS
|
EM
|
HF
|
Yes
|
HWE
|
Handles some
missing data
|
EM issues
|
3 loci, biallelic/
multiallelic
|
PC/UNIX
|
[46]
|
| | | | |
Various tests
available
| | | | |
| | | | |
Improves with
increasing sample
size
| | | | |
2. Simple Bayesian
| | | | | | | | | |
HAPLOTYPER
|
MC+PL
|
HA/HF
|
Yes
|
HWE
|
Uses PL algorithm
to construct haplotypes with many
loci
|
Long run times
|
256 max,
biallelic
|
UNIX
|
[57]
|
| | | | |
Provides posterior
probabilities for
assigned haplotypes
|
Posterior
probabilities may
be difficult to
interpret
| | | |
HAPLOREC
|
MC-VL
|
HA/HF
|
Yes
|
HWE
|
Uses variable
length chain based
on maximising LD
|
Restarts avoid
non-global
optimum
|
Practical
limit,
biallelic
|
Java
virtual
machine,
v1.4
or newer
|
[62]
|
| | | | |
Handles large
number loci
| | | | |
3. Coalescent-based Bayesian
e
| | | | | | | | |
Arlequin v3.0
|
ELB
|
HA/HF
|
No
|
Adaptive
window
|
Includes numerous
population genetics
analyses
|
Long run times
|
1,000 s, biallelic/
multiallelic
|
JRE on
LINUX/
PC/Mac
|
[60, 89]
|
| | | | |
Handles recombination
| | | | |
PHASE v2.0
|
MCMC+PL
|
HA/HF
|
Yes
|
Coalescent/
HWE
|
Improved run time
|
Departure for
coalescent model
may impact performance
|
Practical limit,
biallelic/
multiallelic
|
PC/MAC/
UNIX
|
[59]
|
| | | | |
Compares haplotype frequency
between groups
|
Posterior
probabilities may
be difficult to
interpret
| | | |
| | | | |
Handles
recombination
| | | | |
| | | | |
Provides posterior
probabilities for
assigned haplotypes
| | | | |
PHASE v1.0
|
MCMC
|
HA/HF
|
No
|
Coalescent/
HWE
|
Incorporates
pop-genetics and
coalescence ideas
|
Departures for
coalescent model
may impact performance
|
Practical limit,
biallelic/
multiallelic
|
UNIX
|
[51]
|
| | | | |
Incorporates
known phase and
trios pedigrees into
analysis
|
Slow run times
| | | |
| | | | |
Provides posterior
probabilities for
assigned haplotypes
|
Posterior probabilities
may be difficult
to interpret
| | | |
SLHAP v1.0
|
MCMC
|
HA/HF
|
Yes
|
Neutral
coalescent/
HWE
|
Similar to PHASE
v1.0
|
Departures for
coalescent model
may impact performance
|
Practical limit,
biallelic/multiallelic
|
UNIX
|
[58]
|
| | | | |
Missing data
| | | | |
| | | | |
Improved run time
| | | | |