Evolutionary constraint facilitates interpretation of genetic variation in
resequenced human genomes
David L. Goode, Gregory M. Cooper, Jeremy Schmutz, Mark Dickson, Eidelyn
Gonzales, Ming Tsai, Kalpana Karra, Eugene Davydov, Serafim Batzoglou, Richard M.
Myers, Arend Sidow
Supplemental Material
Supplemental Discussion
SELECTION AGAINST VARIATION IN CONSTRAINED ELEMENTS AND AT
CONSTRAINED SITES
An initial indication of the effectiveness of using evolutionary constraint for evaluating
the discovered variation is the significant underrepresentation of SNPs within constrained
elements (CEs) compared to the flanking neutral regions (hypergeometric P = 1.26 x 10-4;
Supplemental Table 3). Variation in CEs also exhibits a significantly lower average DAF
(Wilcoxon P = 1.97 x 10-9; Supplemental Table 4) compared to neutral regions.
CEs are the usual unit of prediction in comparative sequence analysis (Cooper et al, 2005;
Siepel et al 2005; Asthana et al 2007; Margulies et al 2007; The ENCODE Consortium
2007) but classifying variation at the element, rather than single-nucleotide, level does
not optimally leverage the signal of evolutionary constraint. Sites within CEs can be
under much different levels of constraint (exemplified by synonymous versus nonsynonymous sites within coding exons), and many constrained sites reside outside of
predicted CEs (Asthana et al 2007; Supplemental Table 3). We therefore conducted all
analyses by classifying variation according to site-specific estimates of evolutionary
constraint produced by GERP. For each site in an alignment, GERP calculates a
“Rejected Substitution” (RS) score, so called because it is the estimated amount of
evolutionary variation that was ‘rejected’ by past negative selection (Supplemental
Methods). Classification of our 2214 SNPs by RS provides a substantially and
significantly better signal of both depletion of SNPs and reduction in DAF in constrained
sites than does classification by CEs (Supplemental Table 3), allowing us to extend our
understanding of variation and constraint beyond the results of previous studies that
showed that variation is suppressed in CEs (Drake et al 2006; Asthana et al 2007; Chen et
al 2007; Katzman et al 2007). The reduction in DAF of alleles found at constrained sites
is consistent across multiple annotation categories (Supplemental Figure 7).
Furthermore, negative selection is acting against variation at all DAF levels, with the
strength of selection increasing as DAF increases. We binned all 2214 SNPs according to
their DAF and examined how the SNPs in each bin were distributed with respect to
constrained sites. We found that the number of SNPs at constrained sites in all DAF bins
was fewer than what one would expect to see by chance (Supplemental Figure S2), with
the ratio of the observed to the expected number of SNPs decreasing as DAF increases.
Even SNPs with a DAF < 0.125% (1 SNP in > 800 chromosomes) are under-represented
at constrained sites, indicating negative selection is acting to suppress even the most rare
variants in our sample. Furthermore, as the level of constraint increases, the strength of
selection against variation in all DAF bins increases (compare the four lines in
Supplemental Figure S2).
INDELS
The 124 insertions and deletions (indels) we detected in parallel with the SNPs also avoid
constrained sites. The majority of indels are short, with only 14 (11.7%) having a length
over 5 bp and 48.4% (60/124) of indels having a length of 1 base pair. The longest indel
is a 313 bp deletion of part of the 3’ UTR of the L10 ribosomal protein (RPL10), found in
seven heterozygotes belonging to the Luhya population from Webuye, Kenya.
We ascertained 92 derived alleles that delete a total of 693 bases. Of these, 159 bases
(22.9%) have RS > 1, a significant under-representation of constrained compared to the
fraction of all bases we sequenced that were constrained (51.1% with RS > 1;
hypergeometric P = 8.45 x 10-53). Derived alleles that constitute insertions have, by
definition, no evolutionary constraint and we therefore evaluated the constraint of three
bases on either side of the insertion. Of these 192 sites (representing the six neighbors of
our 32 insertions), 73 (38.0%) are constrained at RS > 1. This is a significant underrepresentation (hypergeometric P = 1.57 x 10-4), showing that insertions avoid
constrained neighbors. We note that excluding coding exons from the indel analysis did
not change the results. Given their relatively small numbers and the uncertainty in
inferring their DAFs, indels were excluded from subsequent analyses.
POPULATION-SPECIFIC ANALYSES
The depletion of variants as RS increases is generally consistent among the five
geographic groups in our sample (Supplemental Figure S3). However, the average DAF
of Europeans and Asians is substantially higher than the DAF of Africans, with the
difference decreasing as RS increases and vanishing at the most constrained positions
(Supplemental Figure S4). This pattern is likely due to historical demographic effects
such as bottlenecking during the migration out of Africa, during which rare alleles were
lost and common alleles increased in frequency (Marth et al 2004; Boyko et al 2008;
Lohmueller et al 2008). The magnitude of the effect is substantial and suggests that
evaluation of variation that focuses only on common alleles systematically
underestimates the amount of functional variation in Africans compared to other
geographic groups.
The average number of derived alleles with RS > 1 carried by African individuals is
virtually indistinguishable from that carried by European or Asian individuals
(Supplemental Figure S5) and differences between the populations only emerge when
genotypes are considered. African individuals carry more derived alleles in the
heterozygous state (data not shown), whereas non-African individuals carry more derived
alleles in the homozygous state (Supplemental Figure S6). Functional noncoding
variation, which is present in our dataset in proportions that are roughly representative of
the whole genome, therefore appears to behave similarly to coding variation with regards
to its distribution among human populations (Lohmueller et al 2008).
FALSE DISCOVERY RATE ESTIMATES FOR CONSTRAINED NONCODING
SITES
The sites we identify as constrained are a mixture of truly constrained sites and neutrallyevolving sites that appear constrained by chance (Cooper et al 2005; Eddy 2005). If this
false discovery rate is dramatically higher for noncoding sequence than it is for coding
sequence, this could explain the preponderance of noncoding SNVs we observe at
constrained sites in an individual’s genome. To investigate this possibility, we applied an
FDR of 0 to all coding sites. That is, we took every coding site that had a RS > 2 to be
truly constrained.
We then estimated the fraction of noncoding sites that could appear constrained by
chance by using the Poisson distribution. For each aligned site the number of
substitutions expected to be observed at that site (E) is equal to the neutral rate of
evolution of the tree connecting the species present in the alignment at that site. For each
discrete value of E found at the 1,301,261,424 noncoding sites having an E > 2, we used
the Poisson distribution with a gamma equal to E to calculate the probability of a site
with that E having a RS > 2 by chance. This probability was multiplied by the total
number of sites with that E to get the number of sites with RS > 2 expected by chance for
sites with that E. This led to a genome-wide estimate of 164,146,071 non-exonic sites
having RS > 2 by chance, suggesting that up to 65% of all noncoding sites with RS > 2
(252,819,327) could appear constrained by chance. Thus, the number of “truly
constrained” non-coding sites as predicted by our Poisson modeling (88,673,256)
represents only 2.8% of the genome. This number and the fact that exons comprise only
about 1.1% of the genome suggest a strict Poisson model may be too conservative.
We also obtained an estimate of FDR using a stricter cutoff for constraint (RS > 4). There
are 35,428,081 non-exonic sites with RS > 4 in the genome, whereas only 4,603,204 are
expected to be observed by chance. This gives an FDR of 13% for noncoding sites with
RS > 4. This indicates that Even if our inferences based on SNVs with RS > 2 are
influenced by a high FDR at noncoding sites, the importance of non-coding and common
alleles in human functional variation is demonstrated by the preponderance of noncoding
and common variants at sites with RS > 4, where the FDR is much lower.
Supplemental Figures
Supplemental Figure S1: Mean derived allele frequency by RS score, for sites harboring
SNVs (black diamonds) and sites one base 3’ of a SNV (blue circles) or one base 5’ of a
SNV (green circles).
Supplemental Figure S2: The ratio of observed number of SNPs at constrained sites to
the number expected by chance for SNPs in six DAF bins, using four different RS cutoffs
to define “constrained” sites.
Supplemental Figure S3: Ratio of the observed to the expected number of SNPs in each
RS bin, in five geographically distinct populations. RS bins were obtained by ranking
SNPs at positions with a RS > 0 by RS score and dividing into quintiles (each group
contains 20% of the SNPs with RS > 0). The expected number of SNPs in each bin was
calculated by considering what fraction of the 227,252 sites we resequenced fall into each
RS score range.
Supplemental Figure S4: Mean DAF of SNPs at constrained positions, in five
geographically distinct populations. RS bins were obtained by ranking SNPs at positions
with a RS > 0 by RS score and dividing into quintiles (such that each group contained
20% of the SNPs with RS > 0).
Supplemental Figure S5: Number of derived alleles carried per individual, in each
population. Horizontal bars correspond to the 10%, 50%, and 90% quantiles.
Supplemental Figure S6: Number of homozygous derived genotypes carried per
individual, in each population. Horizontal bars correspond to the 10%, 50%, and 90%
quantiles.
Supplemental Figure S7: Mean derived allele frequency (DAF) of SNPs in each of five
annotation categories at sites with RS <= 1 (unconstrained) and RS > 1 (constrained).
Supplemental Tables 1 – 4
Supplemental Table 1: Negative selection acts against variation at constrained sites in
all three individual genomes. The number of SNPs observed in each RS bin in each
individual genome, relative to the number expected given the percentage of the whole
genome that falls into each RS bin. Sites for which RS could not be measured due to
insufficient sequence depth were placed in the ‘RS < 0’ bin. SNPs in each genome were
binned according to the RS score of the site where they were found and the number of
SNPs in each bin was compared to the number of SNPs expected in each bin, which was
calculated by multiplying the percentage of the whole human reference genome that falls
into each RS score bin by the total number of SNPs observed in each individual. All bins
with a RS score > 0 have fewer than expected SNPs, and as the RS score range increases,
SNPs become more and more under-represented.
Whole Genome
# of sites
% of sites
Individual
Genomes
# SNPs
Chinese
Observed
Expected
Total
3080419480
<0
1565352986
50.82%
RS bin
0 to 2
1241001096
40.29%
2 to 5
257201259
8.35%
>5
16864139
0.55%
Total
3237659
<0
1721913
1645256
0 to 2
1145638
1304348
2 to 5
180103
270330
>5
4951
17725
0.88
1127298
1301487
0.67
170700
269737
0.28
4868
17686
Venter
Observed/Expected
Observed
Expected
3230557
1.05
1752123
1641647
Yoruba
Observed/Expected
Observed
Expected
3568675
1.07
1880205
1813466
0.87
1273104
1437703
0.63
202144
297968
0.28
5539
19537
1.04
0.89
0.68
0.28
Observed/Expected
Supplemental Table 2: The number and percentage of bases sequenced from the
ENCODE regions and of the SNPs at constrained positions that are coding and noncoding, using two RS score thresholds. RS > 3 is a more stringent threshold for constraint
than is RS > 1.
Supplemental Table 3: Variation is significantly depleted at constrained sites both
within and outside of constrained elements. The number of sequenced bases or SNPs
within constrained elements and/or at constrained positions (defined as having a rejected
substitutions (RS) score > 1), with the total number of sequenced bases or SNPs given in
parentheses. P-values were obtained from the hypergeometric distribution.
Supplemental Table 4: SNPs in CEs also exhibit significantly lower average derived
allele frequencies (DAF) than SNPs in neutral regions. The mean DAF of SNPs
within/outside constrained elements (top row) and/or at constrained (RS >
1)/unconstrained positions (RS 1). Mean DAF is expressed as a percent (%). P-values
were obtained using the Wilcoxon rank-sum test.
Supplemental Methods
Resequencing
DNA Samples
DNA was obtained from the Coriell Cell Repositories (http://ccr.coriell.org/Default.aspx)
for 432 individuals from 5 populations: Yoruba from Ibadan (YRI; 121 individuals),
Nigeria, Luhya from Webuye (LWK; 90 individuals), Kenya, CEPH (CEU; Utah
Residents with Northern and Western European Ancestry) (75 individuals), Han Chinese
from Beijing (CHB; 73 individuals) and the Japanese from Tokyo (JPT; 73 individuals).
All individuals were unrelated. Overall, an equal number of males and females were
resequenced, with nearly equal numbers of both in each population. A complete list of
samples, including the Coriell catalog ID for each sample, is given in Supplemental Table
6. A complete list of the Coriell plates from which our samples were obtained is given in
Supplemental Table 7.
PCR Primer Selection
A total of 575 regions (74 -1427 bp, median length 463 bp) were selected for PCR
amplification and resequencing from the set of ‘merge6’ constrained elements identified
from multiple alignments of the ENCODE regions using GERP 1.03, and from a subset of
sequences from the ENCODE regions that were found to have promoter function in a
high-throughput transient transfection luciferase reporter assay (Cooper et al 2006). For
the location of each resequenced region, see Supplemental Table 8. For more information
on constrained element detection please refer to the ‘Measures of Constraint’ section
below.
Amplicons were designed using Primer3 (Rozen and Skaletsky 2000), with primers
selected from the neutral DNA flanking constrained elements, using sequence masked by
RepeatMasker (Smit et al 1996-2004). If a suitable pair of primers could not be found
after this first attempt, the left side was masked as above but the right side was masked
for low complexity sequence only, by running RepeatMasker with the " -s -noint" option.
If that also failed, another attempt was made, with the left side masked for low
complexity only and the right side fully masked. The parameter $pcrhighsize was
initially set to 600 bp, and increased if necessary. The Primer3 parameters used were:
PRIMER_MAX_SIZE=24
PRIMER_OPT_SIZE=21
PRIMER_PRODUCT_SIZE_RANGE=400-$pcrhighsize
PRIMER_PRODUCT_OPT_SIZE=500
PRIMER_NUM_RETURN=1000
PRIMER_OPT_TM=62
PRIMER_MIN_TM=59
PRIMER_MAX_TM=65
PRIMER_MIN_GC=25
PRIMER_MAX_GC=60
PRIMER_SALT_CONC=50
PRIMER_DNA_CONC=50
PRIMER_SELF_ANY=8
PRIMER_SELF_END=3
PRIMER_MAX_POLY_X=3
PRIMER_GC_CLAMP=0
PRIMER_MAX_END_STABILITY=8
PRIMER_PAIR_WT_PRODUCT_SIZE_LT=1.2
PRIMER_MAX_TEMPLATE_MISPRIMING=12
PCR Amplification
DNA samples were arrayed onto plates and PCR amplification performed simultaneously
on each sample. Samples were amplified in two batches comprising 48 and 384 samples.
The reaction volume in each well was 5.5 L, comprising 1 L DNA (5.0 G/L), 0.5
L each of the forward and reverse primer (10 M), 1 L 5X PE Taq Gold Buffer, 0.4
L dNTPs (2.5 M), 0.035 L of Amplitaq Gold (PE) (5U/L) and 2.065 L H20. The
following cycling conditions were used for PCR: 10 minutes at 95˚C, followed by 35
cycles of 30 seconds at 94˚C, 30 seconds at 63˚C and 23 seconds at 72˚C, and finishing
with 3 minutes and 30 seconds and 72˚C. PCR products were kept at 4˚C after the
reaction was completed. After PCR, products were cleaned up using 10 U of exonuclease
I and 1U of shrimp alkaline phosphastase in a 2.0 L reaction volume.
Sequencing
For each sample on the PCR plate, 1.0 L of DNA was taken and combined with 1.0 L
primer (10 uM), 1.0 L 50% BigDye Terminator v3.1 mix, 1.0 L 2.5X BigDye
Terminator v1.1, v3.1 Sequencing Buffer and 1.0 L H20. The following cycling
conditions were used for sequencing: 5 minutes at 96˚C, followed by 30 cycles of 10
seconds at 96˚C, 5 seconds at 50˚C and 4 minutes at 60˚C. Samples were kept at 4˚C after
the sequencing was completed. Data was collected using an ABI 3730XL with 50cm
arrays. Sequencing was performed at the Stanford Human Genome Center.
Identification and verification of SNPs and indels
All sequencing reads were visually inspected for quality and acceptable reads from each
region were assembled using Phrap v.990319 (Ewing and Green 1998; Ewing et al 1998).
SNPs were identified using PolyPhred 5 (Stephens et al 2006) and all SNP calls were
confirmed by visually inspecting all PolyPhred SNP calls using Consed (Gordon et al
1998). Indels were identified through visual inspection of reads.
To estimate our false positive rate for single heterozygotes, we selected 84 SNPs for
which a single heterozygote was found and resequenced the heterozygous individual
using the same primer combination used in the first round of sequencing. Heterozygosity
was confirmed for 72 (85.7%) of these SNPs, indicating 14.3% of our single heterozygote
SNPs are false positives. This implies that of the 936 single heterozygote SNPs for
which we could ascertain the derived allele, 125 are false positives. Though single
heterozygotes are the largest category of SNPs in our data set, they make up a small
fraction (936/46690, 2.0%) of the total number of heterozygous sites we sequenced.
We do not anticipate that error in identifying heterozygotes should have a large effect on
the derived allele frequencies (DAFs) of more common alleles, as there is a probability of
0.02 of seeing two false positive heterozygotes at a single locus, a probability of 0.0029
of seeing three false positive heterozygotes at a single locus, and this probability rapidly
becomes negligible as the number of expected false positive heterozygotes increases. We
did not observe an increased tendency to misidentify heterozygotes in any one
population, relative to the others.
Processing of SNP and indels
After visual inspection of SNP calls, 2688 SNPs and 144 indels were confirmed in at
least one individual. From this set we removed any SNP or indel that was not genotyped
in at least 80% of the individuals (ie, having a “no-call” rate of > 20%) in every one of
the 5 sample populations or was at a position with a neutral rate lower than 0.25
substitutions per site, as these positions are too shallow for reliable measurement of
constraint (see ‘Measures of Constraint’ below). As well, all data from two individuals
(NA19098, from the YRI population, and NA19085, from the JPT population) was
removed from the study, as the genotyping of these individuals failed at > 20% of their
loci. After this step, a set of 2573 SNPs and 134 indels remained. A summary of the
number of SNPs found in each sample population is given in Supplemental Table 9.
The location within the ENCODE regions of all SNPs, indels and resequenced regions
was determined using Blat19. The derived allele for each SNP was ascertained by
comparison to the aligned position in baboon and chimpanzee (see ‘Alignments’ below).
SNPs at positions where the sequence differed between baboon and chimpanzee, or
where data was missing for one of the species, were removed from further analysis.
Likewise, resequenced regions without at least one SNP for which the derived allele
could be ascertained were also excluded. This left us with 2214 SNPs and 124 indels in
516 regions totaling 227,252 bp in length. All analyses described in this paper were
performed using this trimmed data set.
The 2214 SNPs in the final data set are listed in Supplemental Table 10, with their
locations, derived allele frequencies in each of the sample populations and annotations.
Alignments
Multisequence alignments for each of the 44 ENCODE regions were constructed using
the Threaded Blockset Aligner (TBA) program (Blanchette et al 2004; Margulies et al
2007), using the September 2007 ENCODE sequence data freeze. In this set of
alignments, the non-human sequences have been reordered to be syntenic with the human
sequence, such that all human bases are present in each alignment and have at most one
aligned nucleotide from each other species. Further details about the alignments can be
found in Margulies et al (Margulies et al 2007).
We processed these alignments by removing all non-mammalian species and any species
which had extensive gaps or was which could be aligned to <50% of the ENCODE
regions. Each alignment contains 24 – 26 mammalian species. As well, we removed
from the alignment any positions that were gapped in human, in order to make the human
sequence continuous. Gaps were permitted in other species, however.
Measures of constraint
A recently finished, improved version of Genomic Evolutionary Rate Profiling program
(GERP 2.1, http://mendel.stanford.edu/SidowLab/downloads/GERP/index.html) was
used to obtain the site-specific estimates of constraint and constrained elements (CEs)
used in this study. The processed alignments described in the previous section were used
as input for GERP, along with the neutral tree for the species in the alignment. The
branch lengths of the neutral tree were calculated using four-fold degenerate sites.
For each position in an alignment GERP calculates a “Rejected Substitutions” (RS) score,
which is the difference between the number of substitutions expected at that position
given the neutral distance between the species present in the alignment at that position
and the number of substitutions observed at that position. The neutral distances to species
that are gapped (ie not present in the alignment) at that position do not contribute to the
calculation of the RS score. A positive RS score reflects a deficit of substitutions,
implying that a position is under constraint, at the evolutionary scale covered by the
alignment. For the alignments used here, the maximum possible RS score is 4.22,
reflecting the depth of the neutral tree relating the aligned sequences. Adjacent
constrained positions are aggregated and labeled as a constrained element if their
cumulative score exceeds that expected by chance for a random sample of positions with
the same size as length of the putative element. Further details on the calculation of RS
scores and identification of constrained elements can be found by downloading the GERP
2.1 documentation at http://mendel.stanford.edu/SidowLab/downloads/gerp/index.html.
Annotations
Annotations from the “RefSeq Genes” track were downloaded from the from the UCSC
ENCODE browser (Karolchik et al 2008), for version hg18 of the human genome, and
used to annotate each base in each ENCODE region. Each base was annotated as
belonging to a coding exon, an intron, a UTR or as intergenic if it did not fall into any of
these three categories. SNPs in coding exons were further divided in synonymous and
non-synonymous, based on the derived allele.
Statistical analysis
All statistical analyses were conducted using R (http://www.r-project.org/)
Supplemental Tables 5 – 11
Supplemental Table 5: Estimates of nucleotide diversity () and  for the ENCODE
resequencing data for evolutionarily constrained sites (RS > 1) and sites that are not
evolutionarily constrained (RS 1).  was estimated from allele frequencies and  was
estimated using Watterson’s estimator (Watterson 1975).
Sequence
 (confidence interval)
Watterson's
estimator for 
Constrained
4.24 x 10-7
1.25 x 10-6
(RS > 1)
(7.22 x 10-6 - 8.41 x 10-7)
Unconstrained
9.54 x 10-7
(RS  1)
(1.87 x 10-6 - 3.60 x 10-8)
1.85 x 10-6
Supplemental Table 6: Description of resequenced individuals. Listed are the Coriell
Catalog ID of each sample and the Coriell Plate ID of the plate each sample was taken
from. Samples came from the following populations: Yoruba from Ibadan (YRI), Nigeria,
Luhya from Webuye (LWK), Kenya, CEPH (CEU), Han Chinese from Beijing (CHB)
and the Japanese from Tokyo (JPT).
Catalog ID
Population
Sex
Plate ID
NA06984
NA06986
NA06989
NA07031
NA07037
NA07045
NA07051
NA07346
NA07347
NA07435
NA11829
NA11830
NA11831
NA11832
NA11843
NA11891
NA11892
NA11893
NA11894
NA11917
NA11918
NA11919
NA11920
NA11930
NA11931
NA11992
NA11993
NA11994
NA11995
NA12003
NA12004
NA12005
NA12006
NA12045
NA12058
NA12154
NA12155
NA12156
NA12236
NA12272
NA12273
NA12275
NA12282
NA12283
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
Male
Male
Female
Female
Female
Female
Male
Female
Male
Male
Male
Female
Male
Female
Male
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Male
Female
Female
Male
Female
Female
Male
Female
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT06
HAPMAPPT06
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT01
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
NA12286
NA12287
NA12340
NA12341
NA12342
NA12343
NA12347
NA12348
NA12383
NA12399
NA12400
NA12413
NA12414
NA12489
NA12546
NA12718
NA12748
NA12749
NA12774
NA12775
NA12776
NA12777
NA12778
NA12827
NA12828
NA12829
NA12830
NA12842
NA12843
NA12889
NA12890
NA18524
NA18526
NA18529
NA18530
NA18532
NA18534
NA18536
NA18537
NA18540
NA18542
NA18543
NA18544
NA18545
NA18546
NA18547
NA18548
NA18549
NA18550
NA18552
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CEU
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
Male
Female
Male
Female
Male
Female
Male
Female
Female
Male
Female
Male
Female
Female
Male
Female
Male
Female
Male
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Female
Male
Female
Male
Male
Female
Female
Female
Male
Male
Female
Male
Female
Male
Male
Female
Female
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
XC01451
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT06
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
NA18555
NA18557
NA18558
NA18559
NA18561
NA18562
NA18563
NA18564
NA18566
NA18570
NA18571
NA18572
NA18595
NA18596
NA18597
NA18599
NA18602
NA18603
NA18605
NA18606
NA18608
NA18609
NA18610
NA18611
NA18612
NA18613
NA18614
NA18615
NA18616
NA18617
NA18618
NA18619
NA18620
NA18625
NA18626
NA18627
NA18628
NA18630
NA18631
NA18634
NA18638
NA18639
NA18640
NA18641
NA18642
NA18643
NA18645
NA18647
NA18740
NA18745
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
CHB
Female
Male
Male
Male
Male
Male
Male
Female
Female
Female
Female
Male
Female
Female
Female
Female
Female
Male
Male
Male
Male
Male
Female
Male
Male
Male
Female
Female
Female
Female
Female
Female
Male
Female
Female
Female
Female
Female
Female
Female
Male
Male
Female
Female
Female
Male
Male
Male
Male
Male
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
NA18747
NA18748
NA18749
NA18757
NA18939
NA18940
NA18941
NA18942
NA18943
NA18944
NA18945
NA18946
NA18947
NA18948
NA18949
NA18951
NA18952
NA18953
NA18954
NA18955
NA18956
NA18957
NA18959
NA18960
NA18961
NA18962
NA18963
NA18964
NA18965
NA18966
NA18967
NA18968
NA18969
NA18972
NA18973
NA18975
NA18976
NA18977
NA18979
NA18992
NA18993
NA19001
NA19002
NA19005
NA19009
NA19010
NA19054
NA19055
NA19056
NA19057
CHB
CHB
CHB
CHB
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
Male
Male
Male
Male
Female
Male
Female
Female
Male
Male
Male
Female
Female
Male
Female
Female
Male
Male
Female
Male
Female
Female
Male
Male
Male
Male
Female
Female
Male
Male
Male
Female
Female
Female
Female
Female
Female
Male
Female
Female
Female
Female
Female
Male
Male
Female
Female
Male
Male
Female
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT02
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
NA19058
NA19059
NA19060
NA19062
NA19063
NA19064
NA19065
NA19066
NA19067
NA19068
NA19070
NA19072
NA19074
NA19075
NA19076
NA19077
NA19078
NA19079
NA19080
NA19081
NA19082
NA19083
NA19084
NA19085
NA19086
NA19087
NA19088
NA19027
NA19028
NA19031
NA19035
NA19036
NA19038
NA19041
NA19044
NA19046
NA19307
NA19308
NA19309
NA19310
NA19311
NA19313
NA19314
NA19315
NA19316
NA19317
NA19318
NA19319
NA19321
NA19324
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
JPT
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
Male
Female
Male
Male
Male
Female
Female
Male
Male
Male
Male
Male
Female
Male
Male
Female
Female
Male
Female
Female
Male
Male
Female
Male
Male
Female
Male
Male
Male
Male
Male
Female
Female
Male
Male
Male
Male
Male
Male
Female
Male
Female
Female
Female
Female
Male
Male
Male
Female
Female
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPPT05
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
NA19327
NA19328
NA19332
NA19334
NA19346
NA19347
NA19350
NA19352
NA19359
NA19360
NA19371
NA19372
NA19373
NA19374
NA19375
NA19376
NA19377
NA19379
NA19380
NA19381
NA19382
NA19383
NA19384
NA19385
NA19390
NA19391
NA19393
NA19394
NA19396
NA19397
NA19398
NA19399
NA19403
NA19404
NA19428
NA19429
NA19430
NA19431
NA19434
NA19435
NA19436
NA19437
NA19438
NA19439
NA19440
NA19443
NA19444
NA19445
NA19446
NA19448
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
Female
Female
Female
Male
Male
Male
Male
Male
Male
Male
Male
Male
Male
Male
Male
Male
Female
Female
Male
Female
Male
Male
Male
Male
Female
Female
Male
Male
Female
Male
Female
Female
Female
Female
Male
Male
Male
Female
Female
Female
Female
Female
Female
Female
Female
Male
Male
Female
Female
Male
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
NA19449
NA19451
NA19452
NA19455
NA19456
NA19457
NA19462
NA19463
NA19466
NA19467
NA19468
NA19469
NA19470
NA19471
NA19472
NA19473
NA19474
NA18485
NA18486
NA18487
NA18488
NA18489
NA18498
NA18499
NA18501
NA18502
NA18504
NA18505
NA18507
NA18508
NA18510
NA18511
NA18516
NA18517
NA18519
NA18520
NA18522
NA18523
NA18852
NA18853
NA18855
NA18856
NA18858
NA18859
NA18861
NA18862
NA18867
NA18868
NA18870
NA18871
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
LWK
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
Female
Male
Male
Male
Female
Female
Female
Female
Male
Female
Female
Female
Female
Female
Female
Female
Female
Male
Male
Male
Female
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPV12
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
NA18873
NA18874
NA18907
NA18908
NA18909
NA18910
NA18912
NA18913
NA18916
NA18917
NA18923
NA18924
NA18933
NA18934
NA19092
NA19093
NA19095
NA19096
NA19098
NA19099
NA19101
NA19102
NA19107
NA19108
NA19113
NA19114
NA19116
NA19117
NA19118
NA19119
NA19121
NA19122
NA19127
NA19128
NA19130
NA19131
NA19137
NA19138
NA19140
NA19141
NA19143
NA19144
NA19146
NA19147
NA19149
NA19150
NA19152
NA19153
NA19159
NA19160
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Male
Female
Female
Male
Male
Female
Female
Male
Male
Female
Male
Female
Male
Female
Male
Female
Female
Male
Female
Male
Male
Female
Female
Male
Male
Female
Female
Male
Female
Male
Female
Male
Male
Female
Female
Male
Female
Male
Female
Male
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
NA19171
NA19172
NA19175
NA19176
NA19178
NA19179
NA19181
NA19182
NA19184
NA19185
NA19189
NA19190
NA19192
NA19193
NA19197
NA19198
NA19200
NA19201
NA19203
NA19204
NA19206
NA19207
NA19209
NA19210
NA19213
NA19214
NA19222
NA19223
NA19225
NA19226
NA19235
NA19236
NA19238
NA19239
NA19247
NA19248
NA19256
NA19257
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
YRI
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Female
Female
Male
Male
Female
Male
Female
Female
Male
Female
Male
Male
Female
Female
Male
Female
Male
Female
Male
Female
Male
Female
Male
Male
Female
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT03
HAPMAPPT03
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
HAPMAPPT04
Supplemental Table 7: List of the Coriell plates from which samples were drawn:
Population(s)
Number of samples
Plate ID
on plate
obtained from plate
HAPMAPPT01
CEU
16
HAPMAPPT02
JPT & CHB
55
HAPMAPPT03
YRI
60
HAPMAPPT04
YRI
61
HAPMAPPT05
JPT & CHB
91
HAPMAPPT06
CEU
58
HAPMAPV12
LWK
90
XC01451
CEU
1
Supplemental Table 8: Chromosomal locations and lengths (in bp) of the regions
selected for PCR amplification and resequencing.
Region
Length (bp)
Chromosome
Start
Coordinate
End
Coordinate
00421.ENm001
00504.ENm001
00535.ENm001
00579.ENm001
00580.ENm001
00690.ENm001
00696.ENm001
00714.ENm001
00721.ENm001
00731.ENm001
00863.ENm001
00873.ENm001
00876.ENm001
00877.ENm001
00878.ENm001
00899.ENm001
00900.ENm001
00902.ENm001
00918.ENm001
00919.ENm001
00925.ENm001
00926.ENm001
00932.ENm001
00933.ENm001
00934.ENm001
00940.ENm001
00942.ENm001
00945.ENm001
00947.ENm001
00953.ENm001
00955.ENm001
00960.ENm001
00964.ENm001
00967.ENm001
00970.ENm001
00973.ENm001
00974.ENm001
00975.ENm001
00977.ENm001
00983.ENm001
00987.ENm001
00989.ENm001
00991.ENm001
00993.ENm001
00999.ENm001
01001.ENm001
01002.ENm001
01005.ENm001
01010.ENm001
204
299
144
220
343
230
401
75
368
359
588
444
139
441
195
120
573
405
120
189
392
271
233
188
561
390
311
197
263
325
440
308
317
135
87
171
481
121
343
301
123
211
542
109
271
211
363
157
234
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
115816627
116100829
116170093
116309134
116315164
116757847
116795718
116903453
116931382
116965288
115933155
116769552
117336777
117372175
117473189
116038950
116224628
116326267
116437695
116195511
116182487
117041806
116016419
117017589
116237542
116030318
117434701
115853627
116222211
117155278
117084100
117308247
116448294
115908431
115928125
116016557
116161424
115824554
116713393
117092667
117435024
117439725
116225368
116139834
116162101
117183808
116641511
116749940
116554448
115816830
116101127
116170236
116309353
116315506
116758076
116796118
116903527
116931749
116965646
115933742
116769995
117336915
117372615
117473383
116039069
116225200
116326671
116437814
116195699
116182878
117042076
116016651
117017776
116238102
116030707
117435011
115853823
116222473
117155602
117084539
117308554
116448610
115908565
115928211
116016727
116161904
115824674
116713735
117092967
117435146
117439935
116225909
116139942
116162371
117184018
116641873
116750096
116554681
01011.ENm001
01012.ENm001
01013.ENm001
01014.ENm001
01019.ENm001
01026.ENm001
01028.ENm001
01033.ENm001
01036.ENm001
01039.ENm001
01043.ENm001
01044.ENm001
01045.ENm001
01048.ENm001
01049.ENm001
01050.ENm001
01053.ENm001
01055.ENm001
01058.ENm001
01059.ENm001
01060.ENm001
01063.ENm001
01064.ENm001
01070.ENm001
01071.ENm001
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01093.ENm002_2_1
01096.ENm002_14_1
01492.ENm002_15_1
01594.ENm002_5_1
01674.ENm002_35_1
00971.ENm003_8_0
00978.ENm003_8_0
01553.ENm003_6_1
01685.ENm003_5_0
01925.ENm003_2_0
01047.ENm004_5_0
01218.ENm004_28_0
01268.ENm004_8_0
01315.ENm004_30_0
01379.ENm004_13_0
01434.ENm004_3_0
01609.ENm004_31_0
01611.ENm004_27_0
01857.ENm004_24_0
01924.ENm004_30_0
01961.ENm004_4_1
02148.ENm004_5_0
02198.ENm004_26_1
02227.ENm004_15_1
02282.ENm004_16_0
00929.ENm005_7_0
01008.ENm005_28_0
01021.ENm005_29_1
01031.ENm005_28_0
01127.ENm005_28_0
01219.ENm005_37_1
665
631
561
437
550
612
434
638
492
419
530
481
571
454
490
629
587
611
564
518
446
454
478
582
517
480
565
493
501
472
498
585
479
475
558
482
601
505
505
463
495
508
521
630
615
617
528
520
470
486
512
498
509
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
5
5
5
5
5
5
5
11
11
11
11
11
22
22
22
22
22
22
22
22
22
22
22
22
22
22
22
21
21
21
21
21
21
117219507
115667186
117382177
116749590
115645428
116491306
115669362
117018519
116557592
116339232
116188999
116509206
116001739
117173141
116205937
115600113
115962693
117304520
115951967
117236495
131423869
131907028
131366775
131722153
131752123
131437023
132229848
116246063
116237178
116205451
116199121
116151060
30388101
31190347
30409225
31237715
30671254
30170555
31732597
31138161
31096937
31228325
30298758
30346917
31112433
30768781
30885180
32906693
33907635
33936159
33935786
33880157
34242660
117220171
115667816
117382737
116750026
115645977
116491917
115669795
117019156
116558083
116339650
116189528
116509686
116002309
117173594
116206426
115600741
115963279
117305130
115952530
117237012
131424314
131907481
131367252
131722734
131752639
131437502
132230412
116246555
116237678
116205922
116199618
116151644
30388579
31190821
30409782
31238196
30671854
30171059
31733101
31138623
31097431
31228832
30299278
30347546
31113047
30769397
30885707
32907212
33908104
33936644
33936297
33880654
34243168
01272.ENm005_36_0
01303.ENm005_25_0
01671.ENm005_14_0
02020.ENm005_17_0
00992.ENm006_40_1
01083.ENm006_46_0
01131.ENm006_3_1
01251.ENm006_23_0
01306.ENm006_24_1
01343.ENm006_28_1
01469.ENm006_35_0
01478.ENm006_20_1
01660.ENm006_24_1
01908.ENm006_21_0
02000.ENm006_37_0
02262.ENm006_25_0
01173.ENm007_15_0
01288.ENm007_11_0
01295.ENm007_17_0
01331.ENm007_12_1
01365.ENm007_4_1
01367.ENm007_26_0
01418.ENm007_33_0
01645.ENm007_17_0
01648.ENm007_38_1
01720.ENm007_19_1
01743.ENm007_11_0
01772.ENm007_21_0
01853.ENm007_12_1
01900.ENm007_42_1
01965.ENm007_28_0
01992.ENm007_9_0
02035.ENm007_16_0
02196.ENm007_16_0
00861.ENm008_1_1
00928.ENm008_19_0
01081.ENm008_23_0
01116.ENm008_29_1
02055.ENm008_26_0
00883.ENm009_1_1
00949.ENm009_7_0
01067.ENm009_17_1
01349.ENm009_14_0
01423.ENm009_8_0
01641.ENm009_20_1
01770.ENm009_7_0
00963.ENm010_5_0
01117.ENm010_6_1
01125.ENm010_10_1
01254.ENm010_14_0
01275.ENm010_6_1
01305.ENm010_19_1
01679.ENm010_4_0
507
636
532
600
502
469
488
476
476
514
489
424
446
477
489
462
462
495
481
489
444
473
484
593
550
481
507
695
462
496
507
495
556
452
521
625
481
581
503
536
465
594
483
621
496
519
538
485
499
391
455
151
457
21
21
21
21
X
X
X
X
X
X
X
X
X
X
X
X
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
16
16
16
16
16
11
11
11
11
11
11
11
7
7
7
7
7
7
7
34209940
33785786
33319086
33417675
153423240
153632930
152820760
153280254
153282468
153313399
153366134
153186390
153279544
153236386
153392844
153290745
59355165
59310772
59384085
59324392
59107508
59541623
59676159
59385284
59846726
59396061
59310158
59433353
59310276
59989167
59568182
59297664
59368608
59360164
1113
199637
336353
387909
363937
4965533
5232541
5602336
5487630
5483321
5667179
5232475
27125610
27127656
27152897
27191295
27121114
27248564
27108816
34210446
33786421
33319617
33418274
153423741
153633398
152821247
153280729
153282943
153313912
153366622
153186813
153279989
153236862
153393332
153291206
59355626
59311266
59384565
59324880
59107951
59542095
59676642
59385876
59847275
59396541
59310664
59434047
59310737
59989663
59568688
59298158
59369163
59360615
1633
200261
336833
388489
364439
4966068
5233005
5602929
5488112
5483941
5667674
5232993
27126147
27128140
27153395
27191685
27121568
27248714
27109272
01338.ENm011_12_0
01416.ENm011_7_1
01596.ENm011_9_1
01599.ENm011_24_1
01662.ENm011_24_1
01788.ENm011_3_0
02162.ENm011_5_1
00981.ENm013_9_1
01495.ENm013_7_1
01797.ENm013_7_1
01863.ENm013_3_1
01038.ENm014_1_0
01419.ENr111_2_0
00930.ENr112_1_1
00856.ENr121_3_0
01654.ENr121_3_0
01712.ENr121_1_1
01626.ENr122_4_1
01834.ENr122_5_1
01902.ENr122_5_1
01164.ENr131_1_1
01194.ENr131_1_1
01235.ENr131_6_0
01243.ENr131_1_1
01399.ENr131_5_1
01630.ENr131_7_1
01849.ENr131_3_0
01885.ENr131_1_1
01979.ENr131_1_1
00924.ENr132_12_1
00959.ENr132_12_1
01057.ENr132_9_1
01666.ENr132_12_1
01731.ENr132_4_0
01037.ENr133_3_0
01798.ENr133_5_0
01162.ENr212_1_0
01234.ENr212_1_0
01165.ENr213_1_0
01242.ENr221_3_1
01175.ENr222_2_1
01372.ENr222_4_0
00889.ENr223_12_0
01364.ENr223_10_0
01842.ENr223_4_0
01919.ENr223_5_1
01922.ENr223_11_1
02081.ENr223_6_0
01358.ENr231_2_1
01394.ENr231_6_0
01464.ENr231_13_1
01560.ENr231_7_0
01733.ENr231_13_1
498
471
527
512
533
559
597
661
487
543
558
468
581
448
469
450
645
506
526
500
587
593
492
441
584
572
577
540
505
473
512
491
576
579
521
685
471
478
487
590
519
479
112
565
557
540
564
581
496
467
530
424
502
11
11
11
11
11
11
11
7
7
7
7
7
13
2
2
2
2
18
18
18
2
2
2
2
2
2
2
2
2
13
13
13
13
13
21
21
5
5
18
5
6
6
6
6
6
6
6
6
1
1
1
1
1
1974812
1858091
1900281
2279416
2280060
1735195
1811789
89870140
89813527
89819624
89712006
126670477
29631676
51801380
118482602
118426372
118288159
59528001
59593182
59570906
234264659
234302098
234427824
234333282
234401530
234554758
234317237
234291811
234265913
112746556
112681545
112604108
112794109
112456883
39558665
39640057
141980997
142045722
23786201
56240339
132264368
132494548
74285803
74218534
74076420
74075577
74245934
74161465
149437256
149566717
149813039
149586262
149778992
1975309
1858561
1900807
2279927
2280592
1735753
1812385
89870800
89814013
89820166
89712563
126670944
29632256
51801827
118483070
118426821
118288803
59528506
59593707
59571405
234265245
234302690
234428315
234333722
234402113
234555329
234317813
234292350
234266417
112747028
112682056
112604598
112794684
112457461
39559185
39640741
141981467
142046199
23786687
56240928
132264886
132495026
74285914
74219098
74076976
74076116
74246497
74162045
149437751
149567183
149813568
149586685
149779493
01760.ENr231_1_0
01280.ENr232_8_1
01547.ENr232_3_1
01732.ENr232_5_1
01756.ENr232_5_1
01168.ENr233_5_0
01228.ENr233_16_0
01446.ENr233_13_0
01807.ENr233_11_0
02082.ENr233_1_0
01773.ENr312_3_0
01837.ENr312_1_1
01494.ENr323_5_1
01699.ENr323_2_1
01879.ENr323_7_1
01958.ENr323_3_0
01514.ENr324_2_1
01541.ENr324_1_0
00968.ENr331_11_0
00988.ENr331_15_1
01337.ENr331_15_1
01348.ENr331_8_1
01647.ENr331_7_0
00181.ENr332_5_1
00948.ENr332_20_0
01134.ENr332_11_0
01452.ENr332_20_0
01493.ENr332_12_0
01510.ENr332_24_0
01554.ENr332_23_0
01570.ENr332_17_0
01618.ENr332_12_0
01619.ENr332_24_0
01726.ENr332_16_0
02089.ENr332_11_0
02146.ENr332_7_0
01062.ENr333_10_0
01691.ENr333_16_0
01768.ENr333_5_0
02210.ENr333_4_0
00927.ENr334_1_1
01250.ENr334_5_0
01274.ENr334_4_0
01369.ENr334_10_0
01475.ENr334_2_1
01659.ENr334_2_1
01781.ENr334_8_1
01938.ENr334_6_0
01663.ENm007_10_1
490
541
472
511
614
477
473
518
457
508
568
630
530
537
451
530
585
478
584
490
572
504
480
481
477
457
490
478
529
447
647
442
495
535
453
602
660
461
597
578
538
623
497
491
466
492
599
624
520
1
9
9
9
9
15
15
15
15
15
11
11
6
6
6
6
X
X
2
2
2
2
2
11
11
11
11
11
11
11
11
11
11
11
11
11
20
20
20
20
6
6
6
6
6
6
6
6
19
149429193
130944212
130786688
130862915
130870934
41797089
41904105
41879447
41826496
41572542
130915807
130745243
108593574
108384842
108722399
108491988
122694309
122694479
220132262
220170439
220178719
220086861
220079834
64114476
64380308
64283934
64379042
64291728
64424932
64417419
64355432
64302734
64427278
64334628
64284699
64133766
33629985
33793500
33489224
33463220
41411076
41767053
41766680
41879620
41670272
41662756
41862871
41823014
59297510
149429682
130944752
130787159
130863425
130871547
41797565
41904577
41879964
41826952
41573049
130916374
130745872
108594103
108385378
108722849
108492517
122694893
122694956
220132845
220170928
220179290
220087364
220080313
64114956
64380784
64284390
64379531
64292205
64425460
64417865
64356078
64303175
64427772
64335162
64285151
64134367
33630644
33793960
33489820
33463797
41411613
41767675
41767176
41880110
41670737
41663247
41863469
41823637
59298030
Supplemental Table 9: Summary of SNP and indel data for each population. “Private
alleles” are SNPs found in a single population. “Single heterozygotes” are SNPs in the
rarest class, those found on only one chromosome in a single individual. The numbers of
SNPs and indels in the “Overall” row are less than sum of the numbers of SNPs and
indels found in each population, as SNPs and indels may be segregating in more than one
population.
Population Individuals SNPs
Private
alleles
Single
heterozygotes Indels
YRI
CHB
JPT
CEU
LWK
120
73
72
75
90
1362
719
649
772
1327
409
227
187
301
358
256
192
136
191
246
86
48
44
55
79
Overall
430
2573
1482
1021
134
Supplemental Table 10: Please see GoodeEtAl_TableS10.xls for the set of 2214 SNPs
for which the derived allele could be ascertained.
Supplemental Table 11: The set of 124 indels for which the derived allele was
ascertained. “Start Coordinate” gives the position of the first base of a deletion, or the
base 5’ of an insertion site. Allele frequencies are given as percentages. Indel IDs have
the ENCODE region the indel was found in and it's position within the ENCODE region.
Indel ID
Start
Chromosome Coordinate
Type
Ancestral
Allele
Frequency
Derived
Allele
Frequency
Length
(bp)
ENm001_1003300
chr7
116601056
Insertion
99.88
0.12
1
ENm001_101040
chr7
115698796
Insertion
72.85
27.15
1
ENm001_101834
chr7
115699590
Deletion
98.49
1.51
2
ENm001_1019220
chr7
116616976
Insertion
24.35
75.65
1
ENm001_1059603
chr7
116657359
Deletion
99.88
0.12
1
ENm001_1096931
chr7
116694687
Deletion
89.24
10.76
1
ENm001_1116305
chr7
116714061
Deletion
33.21
66.79
20
ENm001_1117135
chr7
116714891
Deletion
96.47
3.53
13
ENm001_1147044
chr7
116744800
Insertion
52.44
47.56
1
ENm001_1210727
chr7
116808477
Deletion
99.88
0.12
2
ENm001_1309745
chr7
116907501
Deletion
99.88
0.12
2
ENm001_135558
chr7
115733314
Deletion
80.58
19.42
2
ENm001_1369622
chr7
116967378
Deletion
99.88
0.12
8
ENm001_1389126
chr7
116986882
Deletion
99.65
0.35
3
ENm001_1389242
chr7
116986998
Insertion
99.53
0.47
10
ENm001_1417472
chr7
117015228
Insertion
99.88
0.12
1
ENm001_1433168
chr7
117030924
Deletion
99.88
0.12
2
ENm001_1436328
chr7
117034084
Insertion
99.77
0.23
1
ENm001_1496675
chr7
117094431
Deletion
99.88
0.12
31
ENm001_1497669
chr7
117095425
Deletion
99.88
0.12
1
ENm001_1607317
chr7
117205073
Deletion
99.4
0.6
1
ENm001_1612488
chr7
117210244
Deletion
99.88
0.12
2
ENm001_1620567
chr7
117218323
Deletion
0.36
99.64
1
ENm001_1691303
chr7
117289059
Deletion
99.88
0.12
2
ENm001_1725036
chr7
117322792
Deletion
99.88
0.12
4
ENm001_1842400
chr7
117440156
Deletion
97.53
2.47
3
ENm001_184364
chr7
115782120
Deletion
99.53
0.47
21
ENm001_184666
chr7
115782422
Deletion
99.64
0.36
2
ENm001_185147
chr7
115782903
Deletion
3.95
96.05
1
ENm001_185286
chr7
115783041
Deletion
94.95
5.05
3
ENm001_223039
chr7
115820795
Deletion
98.47
1.53
2
ENm001_2713
chr7
115600469
Deletion
90.81
9.19
4
ENm001_323370
chr7
115921126
Deletion
99.76
0.24
1
ENm001_329989
chr7
115927745
Deletion
90.56
9.44
1
ENm001_338353
chr7
115936109
Deletion
99.76
0.24
17
ENm001_341673
chr7
115939424
Deletion
99.88
0.12
2
ENm001_354639
chr7
115952395
Insertion
96.13
3.87
1
ENm001_354719
chr7
115952475
Insertion
98.31
1.69
2
ENm001_357336
chr7
115955092
Deletion
97.74
2.26
1
ENm001_357413
chr7
115955169
Deletion
98.77
1.23
1
ENm001_357557
chr7
115955313
Insertion
36.66
63.34
1
ENm001_357866
chr7
115955621
Insertion
99.88
0.12
1
ENm001_404411
chr7
116002167
Deletion
99.64
0.36
2
ENm001_41344
chr7
115639100
Deletion
55.97
44.03
1
ENm001_418776
chr7
116016532
Deletion
95.43
4.57
2
ENm001_436021
chr7
116033777
Deletion
99.76
0.24
1
ENm001_463370
chr7
116061125
Insertion
0.48
99.52
3
ENm001_48217
chr7
115645972
Deletion
86.32
13.68
1
ENm001_534840
chr7
116132596
Deletion
99.88
0.12
4
ENm001_543766
chr7
116141522
Deletion
99.88
0.12
1
ENm001_547458
chr7
116145214
Deletion
99.65
0.35
4
ENm001_563759
chr7
116161515
Insertion
3.18
96.82
1
ENm001_587421
chr7
116185177
Deletion
99.65
0.35
4
ENm001_591581
chr7
116189337
Deletion
98.66
1.34
2
ENm001_593923
chr7
116191679
Deletion
98.82
1.18
1
ENm001_601329
chr7
116199085
Insertion
93.22
6.78
2
ENm001_615365
chr7
116213121
Deletion
99.18
0.82
2
ENm001_625404
chr7
116223160
Deletion
99.88
0.12
4
ENm001_632768
chr7
116230524
Insertion
99.88
0.12
2
ENm001_64298
chr7
115662054
Insertion
71.22
28.78
2
ENm001_66351
chr7
115664107
Deletion
98.93
1.07
2
ENm001_88096
chr7
115685852
Deletion
56.44
43.56
1
ENm001_88303
chr7
115686059
Deletion
99.64
0.36
4
ENm001_893723
chr7
116491479
Deletion
93.81
6.19
1
ENm002_152927
chr5
131437240
Deletion
99.77
0.23
1
ENm002_622925
chr5
131907238
Deletion
98.01
1.99
1
ENm004_1004585
chr22
31138538
Insertion
80.92
19.08
1
ENm004_1094826
chr22
31228779
Deletion
99.88
0.12
2
ENm004_165297
chr22
30299250
Deletion
4.83
95.17
1
ENm004_36745
chr22
30170698
Deletion
99.3
0.7
3
ENm004_635304
chr22
30769257
Deletion
0.24
99.76
1
ENm005_1117639
chr21
33785875
Deletion
0.35
99.65
1
ENm005_1118150
chr21
33786386
Deletion
99.53
0.47
1
ENm005_650940
chr21
33319176
Deletion
97.56
2.44
4
ENm006_419349
chrX
153186840
Insertion
98.14
1.86
1
ENm006_514992
chrX
153282473
Deletion
99.17
0.83
313
ENm006_655434
chrX
153423278
Deletion
97.54
2.46
1
ENm006_865534
chrX
153633378
Deletion
99.76
0.24
3
ENm007_286690
chr19
59310274
Deletion
99.19
0.81
3
ENm007_287433
chr19
59311017
Deletion
99.88
0.12
1
ENm007_345043
chr19
59368626
Insertion
65.34
34.66
1
ENm007_345102
chr19
59368685
Insertion
0.85
99.15
15
ENm007_360614
chr19
59384198
Deletion
99.77
0.23
2
ENm007_362045
chr19
59385629
Deletion
99.65
0.35
1
ENm007_372784
chr19
59396370
Insertion
99.04
0.96
1
ENm007_410183
chr19
59433767
Deletion
64.69
35.31
3
ENm007_518461
chr19
59542045
Insertion
0.24
99.76
3
ENm007_823333
chr19
59846917
Deletion
99.88
0.12
1
ENm009_496888
chr11
5227883
Deletion
88.54
11.46
4
ENm009_501984
chr11
5232979
Deletion
96.57
3.43
6
ENm009_756832
chr11
5487827
Insertion
28.8
71.2
2
ENm009_871434
chr11
5602429
Deletion
99.64
0.36
1
ENm009_936269
chr11
5667264
Insertion
99.53
0.47
3
ENm009_936586
chr11
5667581
Insertion
99.88
0.12
1
ENm010_197155
chr7
27121200
Deletion
94.79
5.21
2
ENm010_201661
chr7
27125706
Deletion
99.77
0.23
1
ENm010_204029
chr7
27128074
Deletion
99.88
0.12
1
ENm010_324951
chr7
27248996
Deletion
5.19
94.81
1
ENr122_116072
chr18
59528372
Deletion
0.12
99.88
1
ENr131_108512
chr2
234265075
Deletion
66.12
33.88
5
ENr131_145749
chr2
234302311
Insertion
93.26
6.74
14
ENr132_119389
chr13
112457453
Insertion
0.72
99.28
4
ENr133_395759
chr21
39640199
Deletion
23.32
76.68
1
ENr133_395774
chr21
39640239
Deletion
99.87
0.13
5
ENr212_100955
chr5
141981105
Deletion
39.11
60.89
2
ENr212_165801
chr5
142045951
Deletion
14.82
85.18
1
ENr222_46093
chr6
132264632
Insertion
73.67
26.33
1
ENr222_46233
chr6
132264772
Deletion
74.81
25.19
59
ENr223_429072
chr6
74219024
Insertion
99.74
0.26
2
ENr231_12970
chr1
149437654
Insertion
97.18
2.82
1
ENr231_142418
chr1
149567102
Deletion
99.88
0.12
1
ENr231_354372
chr1
149779056
Deletion
91.51
8.49
35
ENr231_354628
chr1
149779312
Deletion
99.88
0.12
4
ENr231_354683
chr1
149779367
Deletion
99.88
0.12
1
ENr232_137971
chr9
130863093
Deletion
99.6
0.4
13
ENr232_146181
chr9
130871303
Deletion
99.88
0.12
1
ENr232_219141
chr9
130944263
Deletion
98.22
1.78
2
ENr233_359735
chr15
41879823
Insertion
98.35
1.65
1
ENr323_120959
chr6
108492355
Deletion
97.29
2.71
5
ENr323_222491
chr6
108593887
Insertion
99.53
0.47
1
ENr331_146953
chr2
220132542
Deletion
99.39
0.61
1
ENr332_362186
chr11
64303074
Deletion
99.88
0.12
1
ENr332_484516
chr11
64425404
Deletion
99.64
0.36
1
ENr333_488867
chr20
33793795
Deletion
99.76
0.24
1
Supplemental References
Asthana S, Roytberg M, Stamatoyannopoulos J, Sunyaev S. 2007. Analysis of sequence
conservation at nucleotide resolution. PLoS Comput Biol 3:e254.
doi:10.1371/journal.pcbi.0030254
Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AF, Roskin KM, Baertsch R,
Rosenbloom K, Clawson H, Green ED et al. 2004. Aligning multiple genomic sequences
with the threaded blockset aligner. Genome Res 14: 708-715.
Boyko AR, Williamson SH, Indap AR, Degenhardt JD, Hernandez RD, Lohmueller KE,
Adams MD, Schmidt S, Sninsky JJ, Sunyaev SR, et al. 2008. Assessing the evolutionary
impact of amino acid mutations in the human genome. PLoS Genet 4: e1000083. doi:
10.1371/journal.pgen.1000083.
Chen CT, Wang JC, Cohen BA. 2007. The strength of selection on ultraconserved
elements in the human genome. Am J Hum Genet 80: 692-704.
Cooper GM, Stone EA, Asimenos G, Green ED, Batzoglou S, Sidow A. 2005.
Distribution and intensity of constraint in mammalian genomic sequence. Genome Res
15: 901–913.
Cooper SJ, Trinklein ND, Anton ED, Nguyen L, Myers RM. 2006. Comprehensive
analysis of transcriptional promoter structure and function in 1% of the human genome.
Genome Res 16: 1-10.
Drake JA, Bird C, Nemesh J, Thomas DJ, Newton-Cheh C, Reymond A, Excoffier L,
Attar H, Antonarakis SE, Dermitzakis ET et al. Conserved noncoding sequences are
selectively constrained and not mutation cold spots. 2006. Nat. Genet. 38: 223-227.
Eddy SR 2005. A Model of the Statistical Power of Comparative Genome Sequence
Analysis. PLoS Biol 3: e10. doi:10.1371/journal.pbio.0030010
Ewing B, Green P. 1998. Base-calling of automated sequencer traces using phred. II.
Error probabilities. Genome Res. 8: 186-194.
Ewing B, Hillier L, Wendl MC, Green P. 1998. Base-calling of automated sequencer
traces using phred. I. Accuracy assessment. Genome Res 8: 175-185.
Gordon D, Abajian C, Green P. 1998. Consed: a graphical tool for sequence finishing.
Genome Res 8: 195-202.
Karolchik D, Kuhn RM, Baertsch R, Barber GP, Clawson H, Diekhans M, Giardine B,
Harte RA, Hinrichs AS, Hsu F et al. 2008. The UCSC Genome Browser Database: 2008
update. Nucl. Acids Res. 36 (Database issue): D773-779.
Katzman S, Kern AD, Bejerano G, Fewell G, Fulton L, Wilson RK, Salama SR, Haussler
D. 2007. Human genome ultraconserved elements are ultraselected. Science 317: 915.
Lohmueller KE, Indap AR, Schmidt S, Boyko AR, Hernandez RD, Hubisz MJ, Sninsky
JJ, White TJ, Sunyaev SR, Nielsen R, et al. 2008. Proportionally more deleterious genetic
variation in European than in African populations. Nature 451: 994–997.
Margulies EH, Cooper GM, Asimenos G, Thomas DJ, Dewey CN, Thomas DJ, Dewey,
CN, Siepel A, Birney E, Keefe D et al. 2007. Analyses of deep mammalian sequence
alignments and constraint predictions for 1% of the human genome. Genome Res 17:
760-774.
Marth GT, Czabarka E, Murvai J, Sherry ST. 2004. The allele frequency spectrum in
genome-wide human variation data reveals signals of differential demographic history in
three large world populations. Genetics 166: 351-372.
Rozen S and Skaletsky. HJ 2000. Primer3 on the WWW for general users and for
biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics Methods and
Protocols: Methods in Molecular Biology. Humana Press, Totowa, NJ, pp 365-386.
Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H,
Spieth J, Hillier LW, Richards S,et al. 2005. Evolutionarily conserved elements in
vertebrate, insect, worm, and yeast genomes. Genome Res 15: 1034-1050.
Smit AFA, Hubley R and Green P. 1996-2004. RepeatMasker Open-3.0.
<http://www.repeatmasker.org>.
Stephens M, Sloan JS, Robertson PD, Scheet P, Nickerson DA. 2006. Automating
sequence-based detection and genotyping of SNPs from diploid samples. Nat. Genet. 38:
375-81.
The ENCODE Consortium. 2007. Identification and analysis of functional elements in
1% of the human genome by the ENCODE pilot project. Nature 447: 799-816.
Watterson GA. 1975. On the number of segregation sites. Theoretical Population Biology
7: 256-276.