3649-08 IICB.indd - Faculty of Biological Sciences - University of ...

Marie-Anne Shaw
BSc (London);
PhD (London);
Postdoctoral research at Cambridge, London School of Hygiene and Tropical Medicine and University of London
Lecturer/Senior Lecturer in Human Genetics (1995–)
Contact: genmas@leeds.ac.uk
Genetic susceptibility
to infectious disease
My primary interest is genetic control
of susceptibility to infectious diseases
and accompanying immune responses.
To what extent does human genetic
variation contribute to susceptibility?
What genes are responsible for
development of clinical disease?
The most interesting questions relate
to severity of disease and
responsiveness to therapy.
The diseases I investigate are prevalent
in the tropics and field work is carried
out in several South American and
African countries. Studies are carried
out both at a population level and using
multicase families.
I have a long-standing interest in
diseases caused by pathogens invading
macrophages, such as tuberculosis
and leprosy. Another such disease
is cutaneous leishmaniaisis, which is
caused by several species of parasite
including Leishmania braziliensis. A
spectrum of immune responses among
individuals is associated with different
clinical manifestations of the disease.
Mathematical analysis of population
data suggests that there is genetic
control of susceptibility to cutaneous
leishmaniasis. A study looking at
severe and disfiguring mucocutaneous
leishmaniasis, which develops in fewer
than 10% of patients who have suffered
from cutaneous leishmaniasis, has
identified a gene which predisposes to
this particular type of disease.
Helminth infections are also associated
with high morbidity worldwide. Different
T-cell subsets are beneficial in defence
against cutaneous leishmaniasis
and helminth infections. The same
genes as those studied for cutaneous
leishmaniasis are being examined
in helminth-infected populations.
An ultimate goal of these studies is
to address how one infection may
influence the severity of a second
disease. My interests also include
gaining a more complete picture by the
study of pathogen genetic variability,
alongside the study of genetic variability
in humans and domestic species.
Figure 1: Mucosal Leishmaniasis
In addition to infectious disease
susceptibility, I work on the anaesthetic
disorder malignant hyperthermia.
An adverse response to inhalational
anaesthetics can cause death. This
is a disorder of Ca2+ homeostasis in
skeletal muscle. The largest collection
worldwide of DNA from patients and
family members is held at Leeds, and
use of this material is revealing the
genetic and functional complexity of
the condition.
Funding: Wellcome Trust,
Department of Health
More information:
http://www.fbs.leeds.ac.uk/staff/profile.
php?staff=MAS
Representative Publications
Carpenter D., Abushama H., Bereczky S.,
Farnert A., Rooth I., Troye-Blomberg M.,
Quinnell R., Shaw M.-A. (2007). Genetic
control of malaria induced antibody responses.
Human Immunology 68, 165-169.
Robinson R., Carpenter D., Shaw M.-A.,
Halsall J., Hopkins P. (2006). Mutations in
RYR1 in malignant hyperthermia and central
core disease. human mutation 27, 977-989.
Booth M., Shaw M.-A., Carpenter D., Joseph
S., Mwatha J., Kabatereine N., Jones F.,
Macbeath R., Ouma J., Dunne D. (2006).
Carriage of HLA-DRB1*13 is associated with
higher IgE responses, and lower re-infection
levels, after praziquantel treatment for
Schistosoma mansoni infection.
J. Immunology 176, 7112-7118.
Quinnell, RJ, Pritchard, DI, Raiko, A, Brown,
AP & Shaw, M-A (2004) Cytokine responses in
human necatoriasis: interleukin-5 responses
are associated with resistance to reinfection.
Journal of Infectious Diseases 190: 430–438
Shaw, M-A, Donaldson, IJ, Collins, A et al.
(2001) Association and linkage of leprosy
phenotypes with HLA class II and class III
genes. Genes and Immunity 2: 196–204