Download 1`! - Blood Journal

From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
Gene
By
Interaction
PHILIP
Resulting
LEVINE,
in Suppression
Substance
B
ELIZABETH
RoBINsON,
AND
Ix
ami
ATTEMPTS
tient.
of Italian
unusual
agglutinin
tested.
The
anti-Tj,
revealed
I.
of antibodies
for
the ABO locus
first described
Bombay.
In the literature
this
the
propositus
and
able
with the serum
by Dr. Bhat.ia
failed
to react
with
animal
origin
(eel
secretor
(lectin)
to react
with
Bhende
anti-H
in the
saliva
and
of amti-H
with
their sera
Bhende
also
et
contained
anti-H.
al.’ suggested
that
t.o be the
easiest
facts
were,
modified
as
series
by
result
zygous
for
in
the
Including
dividuals
siblings
in the
in
the
one
and
4
made
red
‘s
with
(-hickens
amid the
twin
the
In
ram-c
allele
classical
with
that.
at
the
theory
genes
A,
the
of
vam-ieties
framework
the
this
of
agglu-
anti-H
cases
family,
livimig
there
amid
AB()
locus
“appears
of the
AB()
groups.”
Amzel,4
of Hirszfeld
amid 0
B,
propositus,
of
and
are
by
formed
Complete
loss of I-I
B. and
only individuals
produce
anti-H.
unpublished
individuals,
also
anti-Il
seed
of apparently
a
substance
homo-
group
their
sera,
there
am-c now
12 examples,
7 in
studied
by Parkin9
and 3 siblings
in the first.
Bombay
avail-
cells
immul)ize(1
l)lant
siblings
several
,
study.
the
female
basic
published
of
of
imsdividuals
kindly
A individual,
in
cells
in-
()
Imidia,*
2
American
in Providence,
Rhode
Island,
is a history
of cotisamsguimiitv
in
parents.
From
the
Jersey;
the
1)ivision
Institute
Blood
Bamsk
fansily.
saliva
*
These
and
iii
the
wish
Williams
accepted
of
include
,
to
course
to
Orilmo
of Human
Roger
indel)ted
also
I) ‘Seiia
Study
2, 1955;
are
blood
Immunohematology,
the
the
made
They
and
of
Jumly
authors
smmggestiomis
of
for
Submitted
The
fl-bus
formation
present
of
the
living
red
three
patient
as
w-as
allele
europaeus.3
with
a new
such
antil)ody
of a new’
individuals
The
variety
The
serum
H substance.
of gemses 0,., A
and
mutated
genes
could
conpletely
1)0th
react
Watkins5
the
with
anti-H
in
in an Irish family
family
aI)d
ai)d
same
Shiga),2
Ulex
compatible
from
BIIIGGS
factors
scm-a of these
serum,
identical
to
within
Morgan
of mutations
would
failed
however,
of the
product
in the
dysenteriae
-ells of the
explanatiomi
blood
of a group
from
gloup
0,
imcidence
of authors.
serum
Sh.
OuvE
specificity
blood,
the
of the
group
specificity
red
anti-H
chicken
In addition,
apparently
in
rfhe
the
the
normal
Group
for a group
0, Rh
positive
pasuffering
fiom
a kidney
ailment,
with
all rammdomri group
0 bloods
high
individual
of the
serum,
CELANO,
by Bhende
ct al.’ in three
genotype
is i-eferm-ed to as
of a fourth
failed
tiisin
donors
P.,
reacted
or am)ti-e was excluded.
The
anti-H
characteristic
of a rare
at
with
MA1LIXO
Blood
FALKINBURG
to find
compatible
extraction,
Mrs.
was
found
which
occurremsce
anti-k,
as the
LEROY
of
thank
the
husband
the
3 original
a ii(1 2 sih)l i rigs
General
for
1)rs.
of
pul)lication
Ruggero
Col.
of the
cases’,
iii the
Aimgust
of
H.
26,
and
the
for
Ilhmode
New
York;
and
Island.
1955.
Elvin
Kabat
A.
amid
serologic
Crosby
Raritami,
New
University.
Providence,
Ceppellini
Wm.
Foundation,
Coltmmbia
Flospit,al,
discussions
Lt.
Research
Variation,
niaking
genetic
valuable
for
in
findings
available
specimens
this
of
pmopositus.
individual
fansily
1100
cases
st
tidied
Imv hot
st tidied 1my Bhi:i I ia et
:il
,8
hare
et
al
, 6
Sini
-
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
LEVINE
ET
1101
AL.
in
I
0
B
5#{128}
Le(a-b+)
ii
Le(a+b-)
1’!
1
2
le(a-b+)
Le(a-b-)
6
Le(ai-b-)
Le (a+b-)
Le(a4b-)
coniplete
Shia(hiiig
Partial
shadiimg
Se : secretor
2
Le(a+b-)
Ie(a-b+)
homozygous
=
heterozygous
ABH
se : nonsecretor
The
All
of them
‘l’lieim- anti-il
\Vith
all
the
ame
JA’’.
to
m-elu-ts
at
C
l)OsitiVe
out
I l)e basis
foi-
the
genem’atiomms
thee
(as
well
the
By
implicat
The
three
nature
The
with
9 examsiples
su1)s(-mipt.
ion
the
repom-ted
of the
lame
tem-miss
II
iii
sigmiifyiumg
sem’a of Ui,
Isloocls
iii figure
1 am-c
each
fm’omn
gemie
of
is
l)y
factor
the
the
sil)lings,
rare
1)loods.
1 along
with
the
and
am)t,iLeb.
The
3
t.h)e literature)
will
absence
the
would
then
t hei m het.emozygous
amid
homozygous
used
as
tree
for
omi 1)lood
groups,
group
0 1)loods
m-eferred
1)e expected
as
anti-
hem
be
family
unusual
be
anti-
of
is made.
can
data
C.
especially
The
of H sul)stancc
m’epm-esented
\Vith)
more
whi-h
figure
37
I)’Sena,7
pm’oduction
antibody
and
data
of these
at
and
Iea(tiolis
for
umiexpe(-ted
H substamice.
activity
Simmons
distinct.
hi’
the
of
some
in which
and
iii
i-Lem’
retains
described
pamemits,
origimi
ant
iionsecmet.oms
and
indicated
anti_Lcm
‘‘h’’
with
emlvilonment
fom- the
gene
substances
teste(1
(leternuning
item
is pmesemmt.ed
(), bloods
I ramismmtted
as
sigmiifi-ant.
m’ea(-tiomms
as the
Or,,
highly
hypothesis
a
amid
ty)e
Le(a+)
l)moposituis,
mevealed
not
case
Samtgem-,’#{176}the
l)( tiff- iionsecmetom
0
ofis)rimig
se(-ret.iomi,
the
geime
rare
sui)stances
t.elnpelat.ure
of
rare
for
0 am)d are
gm’oup
iii
loomis
or
by
of’ the
stll(lV
l)e
-as
for
ABH
of
11-7
of
ex(-eptiomt
poimited
I I aeais
A
aieai
possible
Lewis
As
1)100(1
1
=
of
Le(a-b?)
iA
Ill
FIG.
Le(a+b-)
to as
pheno-
in the
red cells.
to (-omstaimt
anti-Il.
for
a rare
gemie,
(-om)samiguineous
parents.
The
(his(-ussedl below.
ami(l Ii wei-e
rec-emitly
employed
of the
thami
gem)es whi(-h
tem-mis O, as
the
absema-e
detem-mimie
a phiemiotype
of gemie
II
pm-esence
by
amid
Watkimis
the
the
implies
01’
the
pm-esemice
It is obvious
that
imi the family
of the
logic propem’l ies which
appeal
t.o violate
fim-st
(-1111(1 Ill-i
mior apparemitly
has
the
I)m’escmlt
dommmiamit.
iii the
pm-operty
pliemiotype
amid absence
iii the
presemit
Morgan’#{176}
to
iii-
of the H
substaml(-e.
It
shiou.ild
be emphasized
that
discussion
the term
‘‘0’’
has no refem’cma-e
to ammy gemme, l)ut. it is imitencled
to indicate
a phemiotype
(lefimie(l
by the lack
of Fl substamiee
amid the presence
of anti-Il.
Imi short,
the use
du-ate
of H substamsee
lack
of gene
both
Memideliams
B
of the
on
a basis
other
exhibit
sero-
h..
propositus,
the
m-espectively
itot
chuldremi
dem’ived
mother
of hemedity.
laws
from
Il-fl.
The
the
father
second
The
11-5
child,
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1 102
SUPPRESSION
OF
BLOOI)
GROUP
TABLE
SUBSTANCE
B
1
Secretion
No..
Age
Phenotype
Genotype
Su,ressor
Testsith
. nt,-
iene
_______
___
____
-
is
e
Le
Phe-
typeG6flOtY1)CF
--
-b+
I-i
.
55
0
00
Xx
a
Se
Se?
+
1-2
.
51
B
B?
Xx
a+h-
se
sese
+
+
11-1
11-2
11-3
11-4
.
11-5
.
30
B
BO
X?
it-l)+
Se
Se?
.
29
B
BO
Xi
a-b-
Se
Se?
+
.
27
0,
BO
xx
se
sel
+
Oi
BO
zr
se
se?
+
.
27
29
a+btt+1)
A,
A,O
XX
t+b-
se
sese
+
11-6
.
26
Oi,
BO
xx
a+b-
se
Sese
+
11-7
.
23
B
BO
.V
ti-b?
Se
Set
mit.
111-1
111-2
*
.
5
A,B
A,I1
Vx
a+b-
se
sese
+
.
2
0
00
Xx
1L-I)+
Se
Sese
+
The
numbers
t Inhibition
correspond
of
nt-not
by
given
in
figure
1.
saliva.
tested.
111-2,
is
a secretor
nonsecretors.
of
H
substance
the
Furthermore,
Le(a-f-)
bloods
tion of Mendelian
In
to those
anti-Lea
are homozygous
heredity.
addition,
the
although
both
second
child,
for gene
Lee,
pal-emits
111-2,
this
is
would
phemiotypically
al-c
-)
Le(a
and
if all
constitute
adult.
a third
viola-
*
following
significant
be mentioned:
a. The parents
in generation
I are
b. The identical
twins
11-3 and
facts
coneermiing
this
i-emnarkable
family
may
first cousins.
11-4 (both
the propositus
11-6 have
red cells of siblings
11-3,
addition
anti-H,
11-4, and
to
c. The
individuals
do
not
secrete
H
and
11-6
but
substances
choriom’etinitis)
from
sufferimig
anti-A,
are
in
amit.i-B in their
sd-a.
Le(a+b-);
these
three
as expected
do
they
secrete
Lea
substance.
d. The
remaining
siblings
lI-i,
11-2,
and
11-7
are
B,
group
and
se(-Ietors,
Lea
negative.
With
regard
suspect
to
with
the
usual
The
require
is
by
genetic
bloods. The
*
Ceppellini,”
he
either
eveists
propositus.
A single
may
family
affecting
each
child
differemst.ly,
excluded.
There
is no reason
to suspect
a mutation
would
seem
to be excluded
of
rare
is excluded
hel two children, there S 1)0 reason
to
all other
red cell antigens
am-c compatille
as shown
below
(cf. table
2). With
su(-h
un-
expectatiOl)s
one
further
possibility
the
and
Furthermore,
in
two
for
two
propositus
theoretical
findings
nonmatermty
one
the
nonmaternity.
the
in the
same
generation,
Nondisjunction
absence
explanation
findings
however,
homozygous
of B in the
for
can
systems
as
the
be found
that
has
11-3,
group
11-4,
evidence
genetic
and
to
the
for
explanation
for
of the
violatioms
in a finer
presented
heterozygous.
blood
apparent
siblings
or
an
one
of
indicate
possibility
since
this
identical
father
that
amid
111-1,
11-5.
heredity
the three
8 of the
and
would
twins
A1B child,
the
of
of
nonpatei’nity.
Memidelian
analysis
11-6,
the
adult
imi
group
Oh
9 individuals
Le(a+)
bloods
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
LEVINE
ET
1103
AL.
I
I
00
B?
Xx
xX
?
:ii
Se
se
5
xx
xx
ese
see
:iir
I
A1B
2
00
Xx
xX
se
In
FIG.
2-The
the
propositus,
that
the
schematic
1)100(1
like
Oh are
It is possible
upon
a
of the genes
factor
B and
0 and
group
nonsecl-etors
to explain
the
both
presses
Le(a+)
Le’
of the
the
Lewis
event,
In
indeed
the
above
are
individual
does
and
in the
to
are
imply
not
suppressed
appears
and
its
kind
be
linkage.
l)hieflOtype
50
a nonsecretor.
Le(a+)
provide
may
from
anticipated
by
gene
to the
later
shown
be
ABO
a most.
it might
recessive
of the
nature
in generation
palcI)ts
11-3, 11-4, and
The essential
The
blood
India
when
h)eing
made
in
by
Le (a+).
Even
secretor
of ABH
the
Dr.
suppressor
on blood
exceptional
with
to
Simnsons
if Le (a-),
substances.
full
be
gemie
genetics
it is desirable
at this
to exist
recessive
tune.
between
the
to
be
quite
definite
to
its
nom-mal
In
alty
suppressor
as was
allele
X
l)e-
known
heterozygotes
I-i amid 111-2
of anti-H
scm-a. Similarly
the B factom
and anti-13.
If the gene behaved
as
expression
group
case
to
this
of the
am-c
possible
to detect
selologically
the heterozygote
tests
with
anti-H.
In further
suppom-t
of the
gene is the histoi-y
of consanguinity
iii the
retest
individual
of the
phenotype
of
and
Simmons
in Australia
anti_Le
suppressiomi
status,
sup-
in
I am)d the
11-6.
data
tested
been
reactions
state
bloods
Ceppellini.’3
x is assumed
have
weaker
assun)pt.iomi
of the
secretor
seems
an
knowledge
commitlnents
locus
the presence
of a single
dose
in the
could not be detected
in tests with a variety
in 1-2 behaved
normally
in tests
with anti-H
distinctly
ABH
any
cause
a dominant,
of our
by
homozygous
That
all Oh
relationship
to make
the
family
the
in
secietion.
state
relationship
independence
suppression
ABH
of genetic
not
in this
x which
uncertain
am)d
relationship
its
findings
gene
and
of the
restraint
brilliantly
The
some
view
system
some
Lea,
phenotype
suggest
whatever
*
given
secretion
unusual
of a rare
ABO
gene.
to exercise
by
e
as
of H sul)stance
all the
interaction
would
the
x and
1)100(1
5e
clue.*
based
to
the
behaves
of phenotype
important
se
arrangement
11-6,
6
o
A10
se
and
a specimen
could
and
saliva
which
h)e
of
genes
in the
genotype,
l)’Sena7
is
in
t lie
still
the
rai’e
suppressiomi
7
to
days
be studied.
fresh-b
variety
3 homnozygotes
state
of
in
geno-
transit
from
Aim attempt
is
may prove
to 1)e
Le (a
-
) and
non-
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1104
SUPPRESSION
type,
the
results
are
stlb)stalice
Since
11-1,
possibly
was
with
given
for
the
contributed
is suppressed
secretion
twins
11-3
there
as vet
n
are
Iii
red
the
action
of 11-6
derived
short,
dells
gemse
transmitted
derived
i.e.,
By
of the
from
the
mother
11-4,
in
genotype
the
Xx,
same
token,
11-6
as indicated
suppressed
secretion
for
the
homozygous
in 1-2,
but
The
secretor
gene
by happy
coincidence
the
mentioned
group
above,
also
comnpatible
fom the
Careful
members
titration
folloivimig
by
other
values
of the
obtained
the
theoretical
of the
family
sera
after
and
X
gene
Se
i
findings
in her
phenotype
also
of the
be
but
Sese,
of the propositus
1 hour
mcubatiomt
B in
of the
Se
111-2
in
the
secretor
he
is
must
father
TI-S
The reactions
of the
antigemuc
systems
inK-k,
The
in figure
genera-
omily the
the
expectations.
listed
three
action
secretion
are given
in table
2.
with the Rh-Hr,
MN,
Ss, Fya,
with
expression
1
of the
the
As
are
the
not
also
cludimig
factors
genes
secretion
6 members
and as expected
his red cells are Le(a+).
of the same
6 imidividuals
for the several
and
the
the
may
xx suppresses
mother
father
I-i.
11-6 because
tests
its
that
gene B
does not prevent
child
111-1 who is
by
also a nom)secretor
red cell antigens
blood
Let
1.
suspected
her
but
in the
genotype
and
Figure
this.
genes
the
ABH
in
11-6,
however,
the A1B
also
whose
of
scheme
and
propositus
to establish
from
the
from
11-3,
is probably
of the essential
in figure
2.
represented
secretion
B and secretors,
it was
for B or if heterozygous,
gene,
11-5.
B
to the
xx. The suppression,
its full penetrance
11-4
progeny
inheritance
is
and
and
corresponds
siblings,
()h
father
in the
The
idemitical
The
the
certainly
111-2.
tiomis
3 group
SUBSTANCE
anti_L&
in group
suppressor
by
GROUP
homozygous
by the genotype
of gene B and
heterozygous
plogem)y
are
is either
the
to
and
1 which
11-7
1-2
transmitted
\\.as suppressed
the tmansmission
being
and
mother
BLOOm)
anti_Lea
in Table
11-2,
the
OF
1 and
and
same
table
in
blood
Jka
holds
true
1.
and her two siblings showed the
at roomu ternpem-atui-e
followed
spinmmsg:
Test
Serum
Cells
(titer
l:
__________
________________________________________
of
0
A2
A,
B
16
M. P.
11-3
16
32
64
H.
P.
11-4
32
32
64
S
I.
P.
11-6
32
64
64
32
2
TABLE
Secretion
No.’
I-i
0
1-2
B
A,
Oi
11-5
11-6
Lewis
Rht
MNSs
a-b+
DCe/DcE
MNSs
0
kk
0
a+b-
DCe/DCe
+
k/c
+
se
a+b-
DcE/dce
+
k/c
se
a+b-
DCe/DCe
M Ss
M Ss
M SS
M SS
M Ss
+
+
0
0
k/c
kk
+
k/c
A,B
se
a+b-
DCe/DcE
111-2
0
Se
a-b+
DCe/dce
*
The
in
f
Most
six individuals
Figure
for whom
2.
probable
Jk’
Se
se
111-1
those
-
gemsotype.
antigens
and
ABH
secretions
are
given
correspond
0
0
to
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
LEVINE
The
titers
were
somewhat
values
of anti-H
:256, 1 :256, and 1:32.
respomiding
as
1
The
presence
the
ii)
with
of each
of the
sera of the three
med cells and by
group
specific
ET
IlOs
AL.
lower
after
incubation
in the
three
original
three
specific
for
1 hoimr
Bombay
antibodies,
O, siblings
neutralization
was
at
37
1)loods’
anti-A,
C.
cor-
The
weme reported
anti-B,
amil ammti-H
established
by specific
with
secretor
salivas
absorptiomt
amid purified
A and
B substances
of both
human*
and animal
sources.
suppressor
genotype
xx exerts
its effect
both on the ABH
in the red! cells
sc(-retion
l)ut it has no influence
on the agglutinability
of the several
other
tested,
M, N, D, and!
C. The
suppressor
gene
also
did
mot affect.
the
The
alid
factors
reactiomi
11) tests
specific
antibodies.
with
rabbit
antiserum
the
suppression
With
anticipated
a compensatory
cells amid saliva.
Titration
that
the
that
found
amount
Inhibition
the
whether
or miot the
t.ions. More
of penetrance
tive
cells
propositus
of 11-6
An
6 sela,
the
can
be ol)tained
1000
additional
cells
5 in group
0 and
her
prepared
sera
ram)dlom
sera
read
in group
B reacted
of the presence
of amitiLet.
Only
omse serum,
cells 11-6. This serum
was derived
from
a mother
iii group
0 and in 2 in group
B. Direct
titration
salimic
amid serum
suspended
red
cells
amid B bloods
respectively.
Apparemit.ly,
amid!
in the indirect
alitiglobulili
test
imiactive
was
Of 37
amiti-A
of the
of
gm-oup
seruni
none of the
t.he partially
rabbit
immune
specific
In testing
react.iomis
the
the
were
tested
of 11-6
specific
X 0 mating
for
maternal
seruns
of 1:640
and
childremi
had
neutralized
seiies,
virtue
by
with
oh-
iii ol’dler
In this
cells
was
m-ea(-t
Nega-
B soluble
were
red
to
1 : 512.
A sera.
with
of the
seems
(legmee
failed
with
group
centrifugation.
values
any
was
gross
0,
he
prepama-
the
med
2 childmemm
with
both
1:80
fom A,
hemolytir
matemmial
disease
serum
for A1 amid B bloods.
selected
group
amid anti-B,
propositus.
anti-Le”.
showed
11-4
of all groups
in B
as
complete
to
to detect
after
group
ramige
below.
group
no
same
isolated
in tests
groups,
red
indhicated
showed
amid
with
from
of all
of agglutimiation
one
obtained
have
iii the
it remuains
of which
immunized
eluates
of 600
11-3
titer
species
might
) individluals.
chensically
siblings
were
in the
out in order
as described
the
one
Le(a+
siblings
but
usimsg
anti-B,
of 11-6
random
series
degrees
and
A im)dividuals
anti-B
weaker
cont.aimiing
substances
however,
was
substances
were carried
in the red cells
11-6
red
potent
with
ABH
comitaining
of 16 group
amid
(-ells
substamice
3 Oh siblings
of the
experiments
B amitigen
A sera
with
substamice
to detect.
of the
result
group
anti-B
served.
same
of the
reactions
blood!
substances
secretion
extcmisivc
of the
pooled
amiti-B,
red
ABH
increase
in the amount
of Lewis
and inhibition
studies
with am)tiLet,
of Let
of
The
human
of the
oms the i-cd cells and in the salivas
of normal
experiments
with the salivas
of the three
suppression
with
for
Of
the
B
infants,
0 sera
6 gave
However,
comitaining
remaining
five
three
the
so-called
imumumie
to distimiet
reactions
with
ouie of tl)ese
could!
be attributed
weak
of
group
thent
0
suffering
sera,
four
front
s’ere
hemolytic
which
am)ti-A
the
om
group
to
derived
the
presem-e
fromii
disease.
1)0th
O, bloods
of
mriothers
The
fifth
reacted!
with
the blood
of the propositus
was derived
from a male
imidividlual
who received!
imijeetiomis
of A and B specific
soluble
substamices.
Theme
is iio imidlicatiomt
that the degree
of reactivity
with
red cells ran parallel
to the
dhre(-t titer of anti-B
nor to the titer
of the so-called!
immuumie
anti-B
in tests of the
Oh
*
Supplied
by
l)r.
Elvin
A.
Kabat.
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1106
SUPPRESSION
partially
tiOli
neutralized
Eluates
the
of
for
semum.
BLOOD
This
GROUP
aspect
SUBSTANCE
of the
B
subject
merits
further
light of the findings
with eluates.
front the red cells of the three
siblings
after
group
0 sera (anti-B
1 : 2048)
gave reactions
invest.iga-
in the
especially
one
OF
prepared
active
the exposure
to a titer
of
to
1:4
B hut also
two other
from
B cell
1 : 2 for A1. (Similar
results
were obtained
with eluates
prepared
active
group
0 sera.)
With
the same serum
eluates
front a normal
titers
of 1 : 256 and 1 : 2 for B and A1 bloods
respectively.
This suggests
gave
that
it is the
cross-reactive
antibody
in group
for the greatly
suppressed
B factor
not yet comuplete
and further
studies
of a group
lyt.ic
A mother
whose
group
in the
are
0
sera’4
which
Oh bloods.
The
required
especially
B (or group
AB)
has
weak
affinity
evidence,
however,
is
with the rare serumu
infant
is affected
with
hemo-
disease.
That
the
in part,
effect
may
11-6,
positus,
tered
With
almost
of penetrance
affinity
a failure
after
to
exposure
which
anti-A
he attributable
by
indicated
in the group
0 serum
with the blood
active
hemolytic
is, at least
of the pro-
eluates
0 serum
to a group
caused
complete
to anti-B
obtain
containing
an
equally
high-ti-
disease.
suppression
of the
B antigems,
the
only
manifestation
is some
residual
antigenic
component
which
apparently
the cross-reacting
antibody
in selected
group
0 sera.
for
has
an
DIsCussIoN
The
plified
interpretation
by having
superficial
of the findings
in
available
all members
inspection
of the
factor
andi secretion
two children.
It is greatly
to
phenotype
three
Lewis
nismn
Bolnhay
and ABH
might,
the
credit
bloods,
under
data
this remarkable
family
of the three
generations
figure
in
in the
1 suggest.ed
propositus
of CeppellinP3
anticipated
who,
the
secretion
systems.
special
conditions,
He
the
ozygous
genes
offspring.
The
aie
tral)smitted
on
analyzing
of the
expression
the
further
to include
data
their
also
red
cell
the antigens
0 and/or
although
the respective
family
presented
in this
effects
fully
expressed
B
in her
imi the
of gene
interaction
speculated
that
the same
be extended
and
suppression
full
possibility
Ceppellini13
states
that “in these three
individuals
B do not manifest
themselves
on the red cells,
present
in the genotype”,
and, as shown
in the
cation,
the
amid their
group
was
sunso that
even a
of the
mechaantigens.
A and/or
genes
are
commumsi-
in the
heter-
*
findings
in this family
do not adversely
influence
the usefuimsess
of blood
of disputed
paternity
because
the Oh type of blood
with
suppressed
he readily
detected
by the presence
of anti-H
in the serum.
Assuming
the
in cases
tests
B can
operatioms
of the same
mechanism
in the 9 other
ported
in
the literature,
the specific
blood
factor
only by complete
family
studies.
It appears
that
India.
Blood! group
amstigens
human
heredity
because
frequently
fully
*
of Oh with anti-H
could
be determined
gene
occurs
re-
more
111
expressed
The
examples
suppressed
the suppressor
above
have
been considered
the products
of the
in all instances.
quotation
is
In short,
Ceppellini’s
the
translation
to be luost
genes
involved
degree
from
useful
in the study
of
were believed
to he
of penetrance
his Italian
was
book.’3
consideredi
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
LEVINE
to be imivariahly
complete.
The
group
constitutes
an exception
to this
that
a similar
mechanism
may
other
blood
group
systems.
A
family
is
of the
family
be explained
of cases
Se
ozygous
reveals
tree
AND
in
which
the
anti-H
in addition
apparent
same
0 blood!s
com)t.ainil)g
commumsication
findings,
serologic
it is possible
findings
un
del
e anti-B.
Le
del
and
to anti-A
2 siblings,
apparently
and
Inspection
anti-B.
of Mendelian
heredity
which
can
state
genes
heter-
gene.
he assumed
familia
to operate
examim)e
the
in
9 other
so-called
group
del
arbore
seros
e duo
pote
de
anticorpores
genealogic
que
in le stato
INTERLINGUA
le proposita
0, ha in br
mendelian
ue
IN
que
in
gruppo
hereditate
gets suppressor
in
anti-H.
pmesemstate
parem)temente
tiol)es
propositus
violations
SUMMARIO
Es
in this
of these
unusual
CONCLUSIONS
sera
the suppression
mechanism
may
for
The
their
11)
discussed
oms the basis of a rare suppressor
gene which
in the homozygote
us the propositus
the actions
of gene B and secretion
gene Se. The
are fully
expressed
when
transmitted
to her offspring
who are
suppresses
B and
presented
0, have
1107
AL.
rule. In the light
serve
to explain
SUMMARY
in gi-oup
ET
del
esser
homozygotic
su consanguineos,
anti-H
familia
revela
apparente
explicate
super
le base
supprime
ap-
in ultra
in le proposita
de anti-A
violade un
rar
le action
del
geis B e dcl gen de secretion
Se. Le genes
B e Se es completemente
exprimite
quando
illos es transmittite
al prole del proposita,
proque
le prole es heterozygotic
pro le gems suppressor.
On
le mesme
de sanguines
supponer
que
ims Ic litteratura,
pote
reportate
mechanismo
del
es
gruppo
active
le
in
9 altere
0 continente
casos,
anti-H.
ADDENDUM
After
this
tentiomi
to
manuscript
was
a strikingly
parallel
the alleles
for t.he secretion
types
r sire xi (Ian) yielded
resented
as r/r sile xR/r
ii amid this
Irwin,
M.
in sheep.
factors,
offspring
dam
and
Professor
M.
of suppressor
R.,
R/r
offspring,
but
the
suppresses
the
offspring.
(Rendel,
Evidence
for epistatic
396-408,
1954.)
Genetics
II. Irwin
called
our atgene called
i involving
R and r in sheep.
Thus,
of type R. Genotypically,
homozygous
state
presumnably
appears
in the heterozygote
however,
and
submitted,
example
action
of genes
a mating
the
dam
R/r
of phemio-
mating
is rep-
is of genotype
expression
of R which,
J., Sorensen,
A. N.,
for
antigermic
substances
39:
REFERENCES
Y. M.,
‘BHENDE,
W.
T.
J.,
R.:
GRUBB,
Some
et Microb.
Boyn,
WATKINS,
Lamicet
system.
2
AND
W.
secretors
1195-1198,
1: 903-906,
aspects
Scand.
C.,
C. K.,
W. M.:
DESHPANDE,
AND
and
1954.
H. M.,
II., RACE, II. H.,
SANGER,
blood-group
“new”
character
related
to
MORGAN,
the
ABO
1952.
of the
Supp.
con)l)lexity
of the
human
ABO
blood
groups.
Acta
Path.
84, 1949.
E.:
SHAPLEIC;mr,
nonsecretors
I3HATIA,
A
by
Separation
use
of
a
of
l)laflt
individuals
agglutinin
of
(Lect.in).
any
blood
group
Blood
9:
No.
into
12,
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1108
SUPPRESSION
L.,
HIRSZFELD,
OF
R.:
AMZEL,
AND
des pleiades.
Ann. Inst.
W. T. J., AND
MORGAN,
J. Exper. Path.
KOTHARE,
B. V., BHATIA,
Brit.
6
case.
SUBSTANCE
pleiades
B
“isoseriques”
386-414,
W. M.:
of the
du
sang.
Sur
l’heredite
1940.
The
so-called
detectioim
0
of a product
substance
to
the
of
the
blood
agglutinogens
group
A and
B.
1948.
159-173,
H. M., SUKUMARAN,
P. K.,
BHATIA,
PARKIN,
SANGHVI,
AND
L.
I).:
Unpublished
H. M., SANGHvI,
Paper
DOROTHY:
Paris,
R.:
presence
September,
anti-O
of
of human
blood
R.:
m2 CEPPELLINI,
International
NASSO,
I.S.M.S.B.,
specimens,
L. D.,
presented
0 blood.
J. Indian
M. A.
JHALLA,
H. I.: In preparation, 1955.
Congress
of Blood
Tranis-
24:
No.
AND
MORGAN,
and
secretions.
On the
S.,
at the
the secretioii
in
serum.
human
W. T. J.:
genetics
1952), p. 204.
R. E.: A-B hemolytic
with special
reference
Blood
10:
No.
Vox
International
1, 17-28,
“La
and
observations
78,
group
amitigens
the
and
1952.
on
the
1-2, 1-14, 1955.
Lewis characters:
Paris,
malattia
disease
to the
1955.
170:
0
amid
H characters
5, No.
Transfusion.
F.:
of the blood
Nature
Some
Sang.
of secretor
of Blood
TEzILAcIcH,
AND
Y. G.,
Fifth
between
or anti-H
Congress
BHIDE,
1954.
A relationship
W. M.,
“WATKINS,
“ROSENFIELD,
in group
1955.
fusions.
‘#{176}
SANGER,
G. W. L.: Anti-H
R. T., AND D’SENA,
9, 325-327,
mother.
les
65:
WATKINS,
9:
GROUP
1953.
SIMMONS,
13_,
Sur
Pasteur.
and the relationship
O gene
BLOOD
A faniily
1954.
September,
emolitica
of the newborn.
direct antiglohulin
del
study.
(Milan:
neonato”
Analysis
of
test
and
Fifth
1480
to
cord
the
Ed.
1)lood
group
0
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1955 10: 1100-1108
Gene Interaction Resulting in Suppression of Blood Group Substance B
PHILIP LEVINE, ELIZABETH ROBINSON, MARINO CELANO, OLIVE BRIGGS and LEROY
FALKINBURG
Updated information and services can be found at:
http://www.bloodjournal.org/content/10/11/1100.full.html
Articles on similar topics can be found in the following Blood collections
Information about reproducing this article in parts or in its entirety may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests
Information about ordering reprints may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#reprints
Information about subscriptions and ASH membership may be found online at:
http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of
Hematology, 2021 L St, NW, Suite 900, Washington DC 20036.
Copyright 2011 by The American Society of Hematology; all rights reserved.