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Dr
Lal
ji S
ing
hD
r L
alji
Sin
gh
Dire
ctor
, CC
MB
Hyd
erab
ad, I
ndi
aD
irect
or, C
CM
B H
yder
abad
, In
dia
4,63
5 w
ell d
efin
ed
popu
latio
ns in
Ind
iap
p 532
trib
es (
7.76
%)
72 p
rim
itive
trib
es,
(36
hunt
ers
and
gath
erer
s)
Div
ersi
ties
in:
lang
uage
soci
al s
truc
ture
dres
s an
d fo
od h
abit
mar
riag
e pr
actic
esph
ysic
alap
pear
ance
phys
ical
app
eara
nce
gene
tic a
rchi
tect
ure
Indi
an p
opul
atio
n st
ruct
ure
Mt
i f
t i
th d
iii
f
lti
it
tit
l Mo
st u
niqu
e fea
ture
is th
e divi
sion
of p
opul
atio
n in
to st
rictly
de
fined
hier
arch
ical e
ndog
amou
s cas
tes,
tribe
s and
relig
ious
gr
oups
.g
p
Boun
darie
s of t
hese
subd
ivisio
ns ar
e hig
hly i
mpe
rmea
ble.
In p
ract
ice, a
lthou
gh n
ot in
theo
ry, t
he re
ligio
us g
roup
s like
Mu
slim
s, Ch
ristia
ns, S
ikhs a
nd o
ther
s rec
ogni
ze en
doga
my
rules
.
The a
bove
feat
ures
, by a
nd la
rge,
appl
y to
each
lingu
istic
regi
on
of th
e cou
ntry
.of
the c
ount
ry.
Lang
uage
form
s stro
ng b
arrie
rs fo
r gen
e flo
w be
twee
n su
ch
regi
ons,
even
amon
g th
e cas
tes,
tribe
s or r
eligi
ous g
roup
s of
regi
ons,
even
amon
g th
e cas
tes,
tribe
s or r
eligi
ous g
roup
s of
simila
r or s
ame h
ierar
chy.e
.g. B
rahm
ins o
f A.P
. and
U.P
.
The
firs
tout
ofA
fric
ahu
man
The
fir
st o
ut o
f Afr
ica
hum
an
From
the u
nfor
givin
g co
ld o
f the
Arc
tic tu
ndra
to
th b
li
ht
f th
At
li
t bk
d th
e blaz
ing
heat
of t
he A
ustra
lian
out b
ack a
nd
the h
umid
fore
sts o
f the
Am
azon
, our
own
sp
ecies
Hom
o sa
pien
s pen
etra
ted
ever
y cor
ner
of th
e glo
be, s
ucce
edin
g in
an u
nriva
lled
arra
y g
,g
yof
envir
onm
ents
.
Wha
t cau
sed
them
to ex
plod
e out
of A
frica
whe
n th
ey d
id?
Wha
t circ
umst
ance
s sud
denl
y allo
wed
they
did
? W
hat c
ircum
stan
ces s
udde
nly a
llowe
d th
ose e
arly
hum
ans t
o sm
ash
down
their
bo
unda
ries l
ike n
o sp
ecies
bef
ore o
r sin
ce?
boun
darie
s like
no
spec
ies b
efor
e or s
ince
?
East
Afri
can
meg
a dro
ught
sbet
ween
135
and
75 th
ousa
nd ye
ars a
go, w
hen
the w
ater
vo
lum
e of t
he la
ke M
alawi
was
redu
ced
b y at
y
least
95%
coul
d ha
ve b
een
the r
easo
n fo
r the
ir m
igra
tion
out o
f Afri
cam
igra
tion
out o
f Afri
ca.
A m
ajor r
ise in
wat
er le
vels
and
shift
to m
ore
jhu
mid
and
decr
ease
d en
viron
men
tal v
ariab
ility
cond
ition
s ove
r muc
h tro
pica
l afte
r ~70
Kyr
ago
cond
ition
s ove
r muc
h tro
pica
l afte
r 70
Kyr
ago
may
hav
e stim
ulat
ed th
e exp
ansio
n an
d m
igra
tions
of e
arly
mod
ern
hum
an p
opul
atio
nsm
igra
tions
of e
arly
mod
ern
hum
an p
opul
atio
ns.
Scho
lz e
t al.
PN
AS
104,
164
16-1
6421
, Oct
ober
200
7
Ro
ma
nia
~4
0K
Alg
eri
a
>3
5K
Ch
i
Isra
el
12
0-9
0K
Po
rtu
ga
l
~2
5K
Ch
ina
~4
0K
25
K
No
rth
ern
Ro
ute
An
dam
an a
nd
Nic
ob
ar Is
lan
der
s
Negr
itos
Mo
ng
olo
id
shor
t sta
ture
dark
skin
pepp
erco
rn h
air
feat
ures
with
Ch
ines
eMa
lays
pepp
erco
rn h
airsc
ant b
ody h
airMa
lays
Burm
ese
Grea
t And
aman
ese
Littl
e And
aman
ese
Cari
Nico
bare
seSh
ompe
n
Cari
Kora
Bo Jeru
Onge
Kede
Kol
Juwo
iPu
cikwa
r
Jara
wa
Pucik
war
Bale
Ben
Sent
inele
se
572
Isla
nds
572
Isla
nds
And
aman
and
N
ib
Il
dA
ndam
an a
nd
Ni
bI
ld
Jara
wa
Gr A
ndam
anes
e
Nic
obar
Isl
ands
Nic
obar
Isl
ands
Sent
enele
se
Gr. A
ndam
anes
e
Onge
Ong
e98
Jara
wa
200
St
l25
0
Ong
e98
Jara
wa
200
St
l25
0
Shom
pens
18
0N
icob
ares
e 2
2,00
0Sh
ompe
ns
180
Nic
obar
ese
22,
000
Nico
bare
se
Sent
enel
ese
250
Gr.
And
a.36
Sent
enel
ese
250
Gr.
And
a.36
Shom
pen
Gen
etic
aff
initi
es a
mon
g th
e tr
ibal
pop
ulat
ions
of
And
aman
and
Nic
obar
Isl
ands
Gen
etic
aff
initi
es a
mon
g th
e tr
ibal
pop
ulat
ions
of
And
aman
and
Nic
obar
Isl
ands
On
ge
Gr.
An
da
ma
ne
se
Jara
wa
Ni
bS
hJara
wa
Nic
ob
are
se
Sh
om
pen
Grea
t And
aman
ese &
On
geOn
gese
ttled
, and
rece
ive
food
ratio
ns an
d ot
her
aid fr
om th
e Ind
ian
Gove
rnm
ent.
Th
ltl
di
if
thT
hlt
ld
ii
fth
Th
e cu
ltu
re, l
ang
uag
es a
nd
ori
gin
of
the
An
dam
anes
e h
ave
bee
n t
he
sub
ject
of
spec
ula
tio
nfo
rce
ntu
ries
Th
e cu
ltu
re, l
ang
uag
es a
nd
ori
gin
of
the
An
dam
anes
e h
ave
bee
n t
he
sub
ject
of
spec
ula
tio
nfo
rce
ntu
ries
spec
ula
tio
n f
or
cen
turi
es.
Blo
od
gro
up
and
pro
tein
stu
die
ssu
gg
est
that
spec
ula
tio
n f
or
cen
turi
es.
Blo
od
gro
up
and
pro
tein
stu
die
ssu
gg
est
that
Blo
od
gro
up
an
d p
rote
in s
tud
ies
sug
ges
t th
at
the
An
dam
anes
e ar
e m
ore
clo
sely
rel
ated
to
O
cean
icp
eop
le
Blo
od
gro
up
an
d p
rote
in s
tud
ies
sug
ges
t th
at
the
An
dam
anes
e ar
e m
ore
clo
sely
rel
ated
to
O
cean
icp
eop
leO
cean
ic p
eop
le.
Ou
rst
ud
yis
the
firs
tm
ole
cula
rd
ata
on
thes
e
Oce
anic
peo
ple
.
Ou
rst
ud
yis
the
firs
tm
ole
cula
rd
ata
on
thes
eO
ur
stu
dy
is t
he
firs
t m
ole
cula
r d
ata
on
th
ese
enig
mat
ic t
rib
es t
o u
nd
erst
and
th
eir
ori
gin
, ev
olu
tio
n a
nd
mig
rati
on
.
Ou
r st
ud
y is
th
e fi
rst
mo
lecu
lar
dat
a o
n t
hes
e en
igm
atic
tri
bes
to
un
der
stan
d t
hei
r o
rig
in,
evo
luti
on
an
d m
igra
tio
n.
gg
Y-SN
P ba
sed
max
imum
par
simon
y phy
loge
ny o
f And
aman
ese
Y-SN
P ba
sed
max
imum
par
simon
y phy
loge
ny o
f And
aman
ese
Onge
Jara
waGA
GAGA
Nico
GAC
urr.
Bio
l. (2
003)
Com
plet
e mtD
NA se
quen
ce an
alysis
of …
5 Ong
e N
ico
bare
se
g5 G
reat
And
aman
ese
5 Nico
bare
seG
t Africa
On
ge/
Gr.
An
da
ma
ne
se
PNG
East
Ind
iaE
ast
Asia
L3
Iden
tified
seve
ral n
ovel
mut
atio
ns, w
hich
are
not f
ound
anyw
here
in th
e wor
ld, in
cludi
ng
our s
urve
y of 6
,500 I
ndian
s
Anda
man
ese a
re th
e des
cend
ants
of t
he fi
rst m
oder
n hu
man
m
igra
ted
out o
f Afri
ca th
roug
h So
uthe
rn C
oast
al ro
ut vi
a Ind
ia ab
out 6
5,000
–70
,000 y
ears
ago.
Whe
reas
the N
icoba
rese
are t
he
rece
nt m
igra
nts f
rom
the S
outh
east
Asia
abou
t 18,0
00 ye
ars a
go.
Mig
ratio
n of
And
aman
ese
Indi
aIn
dia
Afr
ica
Afr
ica
A &
Ni
ld
A &
Ni
ld
isla
nds
isla
nds
Mig
ratio
n of
And
aman
ese
Indi
aIn
dia
Afr
ica
Afr
ica
A &
Ni
ld
A &
Ni
ld
isla
nds
isla
nds
Si
(200
5)Sc
ienc
e (2
005)
Ro
ma
nia
~4
0K
Alg
eri
a
>3
5K
Ch
i
Isra
el
12
0-9
0K
Po
rtu
ga
l
~2
5K
Ch
ina
~4
0K
25
K
So
uth
ern
Ro
ute
65K
An
da
ma
n
&&
Nic
ob
ar
Isla
nd
s
70
–6
5 K
Arc
haeo
log
ical
an
d g
en
eti
c e
vid
en
ce p
oin
t to
a s
ing
le
su
ccessfu
l d
isp
ers
al
acro
ss S
ou
thern
an
d S
ou
theaste
rn A
sia
p
into
Au
str
alia a
nd
wit
h o
nly
a s
eco
nd
ary
an
d l
ate
r d
isp
ers
al
into
Eu
rop
e.
“F
rom
th
e s
ite o
f P
atr
ic in
Weste
rn I
nd
ia,
Jw
ala
pu
ram
in
So
uth
ern
In
dia
, an
d B
ata
do
mb
a-L
en
a i
n S
ri L
an
ka,
these a
re
arc
haeo
log
ical
assem
bla
ges
sh
ow
ing
so
me
str
ikin
garc
haeo
log
ical
assem
bla
ges
sh
ow
ing
so
me
str
ikin
g
resem
bla
nces t
o t
ho
se f
rom
Easte
rn a
nd
So
uth
ern
Afr
ica t
hat
mu
st
be f
rom
very
clo
se t
o t
he p
eri
od
wh
en
mo
dern
hu
man
s
firs
td
isp
ers
ed
fro
mA
fric
a.
Th
ese
po
int
str
on
gly
toa
dir
ect
firs
t d
isp
ers
ed
fro
m A
fric
a.
Th
ese p
oin
t str
on
gly
to
a d
irect
co
nn
ecti
on
betw
een
th
e e
arl
iest
mo
dern
hu
man
co
lon
ists
in
So
uth
ern
Asia
an
d t
heir
pro
bab
le a
ncesto
rs i
n E
aste
rn a
nd
So
uth
ern
Afr
ica”
So
uth
ern
Afr
ica
Nean
dert
hals
were
th
e v
icti
ms o
f earl
y g
en
ocid
e b
y m
od
ern
hu
man
sa
co
nseq
uen
ce
of
ou
rin
here
ntl
yvio
len
tn
atu
reh
um
an
s a
co
ns
eq
ue
nc
e o
f o
ur
inh
ere
ntl
y v
iole
nt
natu
re.
Pau
l Mel
lars
, Sci
ence
(200
6) 3
13, 7
96-8
00
An
As
ian
pe
rsp
ec
tiv
e o
n e
arl
y h
um
an
di
lf
Af
id
isp
ers
al fr
om
Afr
ica
“A
sia
’s e
arl
ies
t h
om
inid
s p
res
en
ce
ha
s b
ee
n
ex
ten
de
d u
p t
o 1
.8 M
yrs
ag
o,
hu
nd
red
of
tho
us
an
ds
of
ye
ars
ea
rlie
r th
an
pre
vio
us
ly
id
Iti
tit
dl
ltti
te
nv
isa
ge
d.
It is
tim
e t
o d
ev
elo
p a
lte
rna
tiv
es
to
on
e o
f p
ala
eo
an
thro
po
log
y’s
mo
st
ba
sic
pa
rad
igm
s:
‘ou
to
fA
fric
a’
”p
ara
dig
ms
: o
ut
of
Afr
ica
.
Ab
se
nc
e o
f e
vid
en
ce
is
no
t e
vid
en
ce
of
ab
se
nc
e.
Den
nell
an
d R
och
rocky, N
atu
re 4
38:
1101-1
104 (
2005)
El
bl
Ea
rly
ma
n b
ec
om
es
ea
rly
ap
e
Cio
ch
on
, N
atu
re,4
59:
910-9
11 (
2009)
So
uth
ern
ro
ute
of
dis
pe
rsa
l o
f m
od
ern
hu
ma
n
ou
t o
f A
fric
a:
Arc
ha
eo
log
ical E
vid
en
ce
g
An
aly
sis
of
the
arc
ha
eo
log
ica
l a
ss
em
bla
ge
s a
t
Jw
ala
pu
ram
in
Ju
rre
ru R
ive
r v
all
ey
of
So
uth
ern
In
dia
imm
ed
iate
ly b
efo
re a
nd
aft
er
the Y
ou
ng
est
To
ba T
uff
(YT
T)
eru
pti
on
re
co
ve
red
fro
m a
rch
ae
olo
gic
al
ind
ustr
ies
fro
mth
esit
estr
on
gly
su
gg
est
the
pre
sen
ce
ind
ustr
ies
fro
m t
he
sit
e s
tro
ng
ly s
ug
gest
the
pre
se
nc
e
of
mo
dern
hu
man
in
In
dia
at
the t
ime
of
the Y
TT
eru
pti
on
wh
ich
occu
rred
in
Ind
on
esia
ab
ou
t 74,0
00 y
ears
ag
o.
Th
is w
as o
ne o
f th
e e
art
h’s
larg
est
kn
ow
nvo
lcan
iceven
ts(2
800
km
3)
kn
ow
n v
olc
an
ic e
ven
ts (
2,8
00
km
3).
Th
e I
nd
ian
su
bco
nti
nen
t co
nta
ins
ex
ten
siv
e Y
TT
de
po
sit
s.
Jala
pra
mP
etra
glia
et a
l. Sc
ienc
e 31
7:11
4-11
6 (2
007)
Jwala
pura
mAn
dhra
Pra
desh
Are
ther
ean
yp
op
ula
tio
n(s
)in
Are
th
ere
any
po
pu
lati
on
(s)
in
mai
nla
nd
Ind
ia, w
ho
are
clo
se
to A
nd
aman
ese?
Hh
ffi
iti
thI
di
Ho
w m
uch
aff
init
ies
the
Ind
ian
p
op
ula
tio
ns
hav
e w
ith
p
pA
nd
aman
ese?
Did
th
e In
dia
ns
con
trib
ute
to
th
eea
rly
hu
man
spre
ad?
the
earl
y h
um
an s
pre
ad?
Wes
t Ben
gal
Et
t
Kera
laW
est c
oast
SW1
Onge
GA9
GA11
GA15
Rajb
ansh
iO2
1O1
9O2
0O4
2
GA8
GA13
O23
Kuru
mba
Grea
t An
dam
anes
eGr
eat
Anda
man
ese
K12
K17
East
coas
tW
est c
oast
Scie
nce
(200
6)GA
15
M3
1b
M3
1a
9617
8108 143
O42
1371
020
07785
1094
085
5346
885.
1+3.
6 Ky
K17
K25
K26
()
1651
916
311
1440
712
876
1101
495
8189
7339
9939
7521
56+A
1613
616
126
1566
714
212
8092
3834
3337 808
152
M3
2a
9.3+
4.7 K
y
1635
716
357
1634
416
344
1631
916
319
1575
415
754
207
207
1919
M3
2b
1629
416
294
1618
916
189
1618
3C16
183C
1617
916
179
1612
416
124
6366
6366
M31
2045
1524
249d
1553
015
440
1117
6
46.3
+10.
9 Ky
1652
616
526
1218
912
189
9064
9064
3817
3817
2156
+A21
56+A
195
195
6366
6366 482
482
45.7
+8.7
Ky
1117
649
07
1504
314
783
1040
048
9M65
+7 K
y21
56A
2156
A14
3814
38
(Aft
ersc
reen
ing
~14
,000
sam
ples
Root
(Aft
er s
cree
ning
14
,000
sam
ples
fr
om 2
40 e
thni
c po
pula
tions
)
Dee
p ro
otin
g lin
eage
s of
Mac
roha
plog
roup
'M' in
Indi
a
BM
CG
enom
ics
(200
6)
Indi
an m
tDNA
poo
l con
sists
of s
ever
al de
ep ro
otin
g lin
eage
s of
BM
C G
enom
ics
(200
6)
Indi
an m
tDNA
poo
l con
sists
of s
ever
al de
ep ro
otin
g lin
eage
s of
mac
roha
plog
roup
M su
gges
ting
in-s
itu o
rigin
of t
hese
hap
logr
oups
in
Sou
th A
sia, m
ost l
ikely
in th
e Ind
ia
Dee
p ro
otin
g lin
eage
s of
Ma
croh
aplo
grou
p 'M
' in In
dia
Bhoi
(M49
)Ta
dvi (M
33A)
Orao
n(M1
8)
Macr
ohap
logr
oup
M in
Indi
a
Khas
i (M48
, M50
)Or
aon (
M18)
Scien
ce (2
005)
BMC
Gene
tics (
2006
)BM
C G
i (2
006)
Pard
han (
M41)
BMC
Geno
mics
(200
6)PL
oS G
enet
ics (2
006)
PLoS
ONE
(200
7)
Rathw
a (M4
A)
Maha
deo K
oli (M
51)
()
GA
d(M
31M3
2)
Hum
Her
ed (2
008)
*M34
A()
Onge
(M31
, M32
)Gr
. And
aman
ese (
M31,
M32)
Paniy
an (M
3)
1 milli
on S
NPs (
Affy
arra
y)
Onge Au
stra
lian
abor
igin
alsDr
avid
ians
Chen
chu
Aust
ro-A
siatic
s
Indo
-Eur
opea
ns
Euro
pean
s
Sant
hal
Khar
ia
Megh
awal
Euro
pean
sHa
pMap
Chin
ese
(Hap
Map)
Megh
awal
In co
llabo
ratio
n wi
th D
avid
Reic
h, D
epar
tmen
t of G
enet
ics, H
arva
rd M
edica
l Sch
ool, U
SA (u
npub
lishe
d da
ta)
Di
tt?
Dis
ease
pat
tern
?
Car
diom
yopa
thie
sC
ardi
omyo
path
ies
Car
diom
yopa
thie
sC
ardi
omyo
path
ies
Ah
tf
ht
lA
hete
rog
en
eo
us g
rou
p o
f h
eart
mu
sc
le
dis
eases, le
ad
s t
o in
ad
eq
uate
pu
mp
ing
of
bl
db
loo
d.
More
than
200 d
iseas
e ass
ociat
ed m
utat
ion
have
Mo
re th
an 20
0 dise
ase a
ssoc
iated
mut
atio
n ha
ve
been
repo
rted
in 20
diff
eren
t gen
es. O
f whi
ch,
MYBP
C3 g
ene i
s inv
olve
d in
abou
t 45%
of t
he to
tal
MYBP
C3 g
ene i
s inv
olve
d in
abou
t 45%
of t
he to
tal
card
iom
yopa
thy.
Delet
ion
of 25
bp M
yosin
e Bin
ding
Pro
tein
-C3 (
MYBP
C3) i
s as
socia
ted
with
Inhe
ritab
le ca
rdio
myo
path
ies in
Indi
an
yp
patie
nts d
ue to
skip
ping
of w
ild ty
pe ex
on (3
3)
Com
bine
d ef
fect
of
asso
ciat
ion
stud
ies
Case
sCo
ntro
lsOR
(95%
CI)
Pn
D, D
D, W
W, W
nD,
DD,
WW
, WOv
erall
In
dia
(n=1
499)
800
5 (0.6)
81
(10.1
)71
4 (8
9.2)
699
012
(1
.7)68
7 (9
8.3)
6.99
(3.63
-13.4
0)4x
10-1
4
D-
dele
ted
allele
;
W-
wild
typ
e a
llele
(n=1
499)
()
()
()
()
()
()
Pos
tmor
tem
tiss
ueP
ostm
orte
m ti
ssue
Ho
mo
zyg
ou
s Pa
tien
ts d
ies
du
e to
hea
rt fa
ilure
Dilat
ion
of th
e lef
t an
d rig
ht ve
ntric
les
Hype
rtrop
hied
myo
fiber
s sep
arat
ed
by in
crea
sed
conn
ectiv
e tiss
ueA
sym
metr
ic h
yp
ert
rop
hy in
vo
lvin
g
Inte
rven
tric
ula
r S
ep
tum
(28 m
m)
g
Myo
fib
rils
co
nsis
t o
f sarc
om
ere
sy
Seven
majo
r p
rote
ins
Exp
ressio
n a
nd
lo
calizati
on
of
cM
yB
P-C
Ex33
pro
tein
s
in N
eo
nata
l R
at
Card
iom
yo
cyte
s (
NR
CM
)
CM
TM
MC
-My
c
a
-TM
M
erg
er
Co
ntr
ol
Co
ntr
ol
Nor
mal
Mus
cle
Stru
ctur
e
WT
Myo
card
ial D
isar
ray
cM
yB
P-C
Mu
tan
t in
Ca
rdio
-
myo
cyte
s
Reco
mbi
nant
aden
oviru
ses
that
expr
esse
dm
ouse
cMyB
P-C
Ex33
(Mut
ant)
were
intro
duce
din
tora
tneo
nata
lcar
diom
yocy
tes
and
imm
unos
tain
edwi
thm
yc-ta
gan
tibod
iesca
rried
only
byth
eWT
and
Muta
ntpr
otein
s(gr
een)
,and
cost
ained
with
- trop
omyo
sin(re
d).
Dis
trib
utio
n of
25
bp d
elet
ion
in I
ndia
6273
sam
ples
107
ethn
ic po
pulat
ions
279
hete
reoz
ygou
s dele
tion
8 ho
moz
ygou
s dele
tion
2 8%
dlt
i (4
35%
)2 –
8% d
eletio
n (4
.35%
)
Pop
ulat
ion
stra
tific
atio
n
No
rth
AP
TN
An
ov
a p
-valu
e >
0.0
5
TN
50
un
lin
ke
d S
NP
ma
rke
rsp
Eu
rop
ean
Hap
Map
Ind
ian
case/c
on
tro
l
Glo
bal d
istr
ibut
ion
of 2
5bp
dele
tion
Glo
bal d
istr
ibut
ion
of 2
5bp
dele
tion
2,0
85 in
dig
en
ou
s i
nd
ivid
uals
fro
m,
g
26
co
un
trie
s
25b
dl
ti
Aro
se ~
33,0
00 y
ears
ago
25b
p d
ele
tio
n
was o
bserv
ed
on
ly in
Pakis
tan
Sri
,y
gP
akis
tan
, S
ri
Lan
ka,
Ind
on
esia
an
d M
ala
ysia
Tro
pica
l cal
cifi
c pa
ncre
atiti
s
In W
este
rn p
op
ula
tio
ns, g
ain
of
fun
cti
on
mu
tati
on
s
pf
p
in c
ati
on
ic t
ryp
sin
og
en
(P
RS
S1)
ge
ne
ha
ve
be
en
as
so
cia
ted
wit
h H
ere
dit
ary
an
d I
dio
pa
thic
ch
ron
ic
titi
Ou
rre
su
lts
su
gg
est
that
rath
er
than
pa
nc
rea
titi
s
Ou
r re
su
lts s
ug
gest
that
rath
er
than
cati
on
ic t
ryp
sin
og
en
gen
e m
uta
tio
ns,
mu
tati
on
sin
its
(i)
acti
vato
rC
ath
ep
sin
Bm
uta
tio
ns in
its
(i)
acti
vato
r C
ath
ep
sin
B
(CT
SB
) an
d (
ii)
inh
ibit
or
SP
INK
1are
asso
cia
ted
wit
htr
op
icalcalc
ific
asso
cia
ted
wit
h t
rop
ical calc
ific
pan
cre
ati
tis (
TC
P)
Varia
tions
that
are n
ot as
socia
ted
with
dise
ase i
n In
dian
s
Cont
inue
d…
Varia
tions
that
are n
ot as
socia
ted
with
dise
ase i
n In
dian
s
Ack
now
ledg
emen
tsIn
dian
colla
bora
tors
K. T
hang
araj
’sG
roup
C
CM
B, H
yder
abad
Indi
an co
llabo
rato
rs
P. S
. Dha
ndap
any
MK
U, M
adur
ai, I
ndia
P. N
alla
riO
sman
iaU
nive
rsity
, Hyd
erab
ad, I
ndia
J. M
. Tha
rkan
Sri C
hitr
aT
IMST
, Tri
vand
rum
, Ind
ia
P. V
aide
esw
erK
EM
Hos
pita
l, M
umba
i, In
dia
M. R
athi
nave
lRaj
ajiM
edic
al C
olle
ge, M
adur
ai, I
ndia
Nal
iniJ
. Gup
ta
B. N
Cha
krav
arth
yIn
st. o
f R
epro
duct
ive
Med
icin
e, K
olka
ta
Mam
thaD
eena
daya
lIn
fert
ility
Ins
t. &
Res
. Cen
tre,
Hyd
erab
ad
G. R
. Cha
ndak
’sG
roup
CC
MB
, Hyd
erab
ad
Ack
now
ledg
emen
tsIn
tern
atio
nal c
ollab
orat
ors
Dav
id R
eich
’s G
roup
Har
vard
Med
ical
Sch
ool,
USA
Inte
rnat
iona
l col
labor
ator
s
p
Chr
is T
yler
-Sm
ithW
T S
ange
r In
stitu
te, U
K
Toom
asK
ivis
ildC
ambr
idge
Uni
vers
ityU
KTo
omas
Kiv
isild
Cam
brid
ge U
nive
rsity
, UK
Eri
ka H
agel
berg
Uni
vers
ity o
f O
slo,
Nor
way
PU
dhi
llS
fd
Ui
iU
SAP
eter
Und
erhi
llSt
anfo
rd U
nive
rsity
, USA
Mar
tin R
icha
rds
Uni
vers
ity o
f L
eeds
, UK
S. O
ppen
heim
erO
xfor
d U
nive
rsity
, UK
Q. A
yub&
Q. M
ehdi
Kha
n In
st. B
GE
, Kar
achi
, Pak
ista
n
