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An evolutionary perspective of how infection drives human genome diversity: the case of malaria.
[alpha-thalassemia]
Infection
with
malaria
parasites
has
imposed
a
strong
selective
pressure
on
the
human
genome
,
promoting
the
convergent
evolution
of
a
diverse
range
of
genetic
adaptations
,
many
of
which
are
harboured
by
the
red
blood
cell
,
which
hosts
the
pathogenic
stage
of
the
Plasmodium
life
cycle
.
Recent
genome-
wide
and
multi-centre
association
studies
of
severe
malaria
have
consistently
identified
ATP
2
B
4
,
encoding
the
major
Ca
(
2
+
)
pump
of
erythrocytes
,
as
a
novel
resistance
locus
.
Evidence
is
also
accumulating
that
interaction
occurs
among
resistance
loci
,
the
most
recent
example
being
negative
epistasis
among
alpha-thalassemia
and
haptoglobin
type
2
.
Finally
,
studies
on
the
effect
of
haemoglobin
S
and
C
on
parasite
transmission
to
mosquitoes
have
suggested
that
protective
variants
could
increase
in
frequency
enhancing
parasite
fitness
.
Diseases
Validation
Diseases presenting
"red blood cell"
symptom
alpha-thalassemia
cholangiocarcinoma
phenylketonuria
severe combined immunodeficiency
zellweger syndrome
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