Download Allgemeine Angaben

Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 1
Supplementary Material for the article:
Kehrer-Sawatzki and Cooper, Human Mutation
Understanding the Recent Evolution of the Human Genome;
Insights from Human-Chimpanzee Genome Comparisons
Hildegard Kehrer-Sawatzki and David N. Cooper
Supplementary Tables S1-S4 and Supplementary Figures S1-S3
Supplementary Table S1: Divergence between humans and chimpanzees in different genic regions
Genic regions
Divergence in %
All nucleotides
Without CpGs
Reference
5'UTR
5’UTR
Coding sequence
Coding sequence
Exon-intron junctions
3'UTR
3'UTR
Intronic
1.12 ± 0.04
1.00 ± 0.10
0.45 ± 0.01
0.51 ± 0.02
0.85 ± 0.02
0.86 ± 0.016
0.93 ± 0.09
1.20 ± 0.014
Hellmann et al. 2003a a
Shi et al. 2003a b
Hellmann et al. 2003a
Shi et al. 2003a
Shi et al. 2003a
Hellmann et al. 2003a
Shi et al. 2003a
Hellmann et al. 2003a
a:
b:
0.77 ± 0.035
0.28 ± 0.008
0.63 ± 0.014
0.80 ± 0.012
Hellmann et al. 2003a investigated 5055 genes
Shi et al. 2003a analysed 127 genes
1
Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 3
Supplementary Table S2: Cancer-related genes with codon insertions/deletions in humans as compared to chimpanzee (according to Puente et al. 2006)
Gene
Gene description
CCNE1
FANCC
FGFR1
HOXD11
ATP2C1
Cyclin E1
Fanconi anemia complementation group C
Fibroblast growth factor receptor 1
Homeobox D11
ATPase, Ca++ transporting, type 2C,
member 1
AF4/FMR2 family, member 1
Myeloid /lymphoid or mixed-lineage
leukaemia translocated to, 3
Meningioma 1
AFF1
MLLT3
MN1
PML
CASC5
ASPSCR1
Chromosome
Amino acid(s) inserted
19q13.1
9q22.3
8p11.2-11.1
2q31.1
3q22.1
type
Serine (S)
Glutamine (Q)
Aspartic acid (D)
Glycine (G)
Glutamic acid (E)
4q21
9p22
Codons inserted in
poly(Q)
poly(D)
poly(G)
poly(E)
chimpanzee





Serine (S)
2 Serines (S)
poly(S)


22q12.1
4 Glutamines (Q)
poly(Q)

15q22
15q14
17q25
Glycine (G), Phenylalanine (F)
Arginine (R)
Glutamic acid (E), Arginine (R)
ATF1
DEK
RNF2
Acute promyelocytic leukaemia
Cancer susceptibility candidate 5
Alveolar soft part sarcoma chromosome
region, candidate 1
Activating transcription factor 1
DEK oncogene (DNA binding)
Ring finger protein 2
12q13
6p23
1q25.3
EP300
E1A binding protein p300
22q13.2
LMO2
AFF1
MYST4
11p13
4q21
10q22.2
NUMA1
LIM domain only 2
AF4/FMR2 family, member 1
Histone acetyltransferase (monocytic
leukaemia) 4
Nuclear mitotic apparatus protein
Alanine (A)
Glutamic acid (E)
Leucine (L), Arginine + Aspartic acid
(RD)
Methionine, Glutamine, Glutamine
(MQQ)
Glycine (G)
Serine (S)
2+1 Glutamic acid (E)
SMO
ZNF38
Smoothened homologue (Drosophila)
Zinc finger protein 38
7q32.3
7q22.1
11q13
Alanine (A)+ Alanine (A)+ Isoleucine
(I)+ Glycine (G)
Leucine (L)
Glutamine (Q)
in repeat
Polymorphic
in humans
humans



poly(ER)


poly(E)
poly(RD)






poly(G)
poly(S)
poly(E)





poly(L)
poly(Q)



3
Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 4
Supplementary Table S3: Human chromosomes that are distinguished by pericentric inversions from their
chimpanzee homologues and the results of breakpoint analyses
HSA chromosome
1
Fixed in the
chimpanzee lineagea
b
Segmental duplications
Reference for breakpoint
found at the breakpoints
characterization
+
Szamalek et al. 2006a
4
+

Kehrer-Sawatzki et al. (2005a)
5
+

Szamalek et al. (2005)
9
+
+c
Kehrer-Sawatzki et al. (2005b)
12
+
+
15
+
+d
Kehrer-Sawatzki et al. (2005c)
Shimada et al. (2005)
Locke et al. (2003a)
16
+
+
Goidts et al. (2005)
17
+

Kehrer-Sawatzki et al. (2002)
18
b
+
Goidts et al. (2004)
Dennehey et al. (2004)
a:
As determined by using other hominoids as an outgroup and summarized in Kehrer-Sawatzki et al. (2005a)
The inversions of chromosomes 1 and 18 were fixed in the human lineage and are therefore human-specific.
c: Segmental duplications were identified at the inversion breakpoint in 9p12.
Adjacent to the breakpoint in 9q, -satellites were detected.
d: Breakpoints were not precisely characterized but narrowed down to regions of segmental duplications.
b:
4
Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 5
Supplementary Table S4: Inversions identified owing to their involvement in human disease
Disease/ syndrome
(gene involved)
Localization
Size of
inversion
Frequency of the inversion in % in
Reference
transmitting parents
(patients)
controls
25-33
5
Osborne et al. 2001 Scherer et al.
2005
Williams-Beuren syndrome
7q11.23
1.5Mb
Angelman syndrome
15q11-q13
4Mb
67
9
Gimelli et al. 2003
Sotos syndrome (NSD1)
5q35.3
1.9Mb
100
67-75
Visser et al. 2005
Recurrent translocation t(4;8)(p16;p23)
Wolf-Hirschhorn syndromea
4p16
8p23
nd
nd
100
12.5
26b
Giglio et al. 2001, 2002
Haemophilia A (F8)
Xq28
400kb
(40)
-
Antonarakis et al. 1995
Hunter syndrome
(idunorate 2-sulphatase, IDS)
Xq28
90kb
(13)
-
Bondeson et al. 1995
Familial juvenile nephronophthisis
(NPHP1)
2q13
330kb
1.3
Saunier et al. 2000
48kb
33
Small et al. 1997
Emery-Dreifuss muscular dystrophy (EMD) Xq28
nd: not defined
a: parents of individuals with t(4;8)(p16;p23) were shown to be heterozygous carriers of inversions at both 4p16 and 8p23. In the offspring of carriers, unbalanced karyotypes lead
to Wolf-Hirschhorn syndrome if the der(4) chromosome is inherited. Patients with unbalanced der(8) show a milder spectrum of dysmorphic features.
b: 2.5%
are double heterozygotes.
5
Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 6
1
2
p33
4
p23-24
8
12
22
p15.1
p12
q12.3
q21.3
57 genes,
from CARD10
to PMM1
14 genes,
from ELAV4
to GPX7
UNC5D,
FKSG2
ARHGAP15,
GTDC1,
ZFHX1B
10genes,
from PAMC1
to ATB2B1
Supplementary Figure S1: Six human chromosomal regions with strong evidence for ‘selective sweeps’ as
indicated by low diversity in humans compared to the divergence in chimpanzee according to Mikkelsen et al.
(2005). On chromosome 4, no genes were identified in the corresponding region.
6
Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 7
Supplementary Figure S2: Frequency of lineage-specific Alu insertions in human and chimpanzee genomes among
all transposon insertions (total numbers of transposon insertions in humans: n= 7786 and n= 2933 in chimpanzee)
according to Mills et al. (2005).
7
Kehrer-Sawatzki and Cooper, Human Mutation
HUMAN MUTATION Supplementary Material Online
Page S 9
Supplementary Figure S3: Frequency of inter- and intrachromosomal duplications on human chromosomes according to Zhang et al. (2005).
9