C O M M E N T
is the 'attachment' molecule then in-
creased binding would be observed
in the Lcr5 cells. However, a sec-
ondary role would be suggested if
binding is equivalent after adsorp-
tion at 4°C and the 10-fold differ-
ence only became evident by shifting
to 37°C; in other words, HAVcr-1
may be an accessory factor prevent-
ing elution from a ubiquitous re-
ceptor. Second, the calcium depend-
ence of HAV binding to Lcr5 and
LDR2 cells should be determined.
If the binding of HAV to LDR2 cells
was nonspecific, as the authors
speculate, then adsorption would be
calcium independent. Conversely,
Lcr5 cells would exhibit calcium-
dependent binding of HAV. How-
ever, if the level is equivalent for
both cell lines it would suggest that
HAVcr-1 has a role after this initial
binding step. It is hoped that further
work will define the precise role of
HAVcr-1 in HAV replication, both
in cell culture and natural hosts.
Raquel U. Cowan and
David A. Anderson
Macfarlane Burnet Centre for
Medical Research, Fairfield Hospital,
Fairfield, Victoria 3078, Australia
References
1 Stapleton, J.T., Frederick, J. and Meyer, B.
(1991)J. Infect. Dis. 164, 1098-1103
2 Zajac,A.J. et al. (1991) J. Gen. Virol.
72, 1667-1675
3 Kaplan,G. et al. (1996) EMBO J. 15,
4282-4296
4 Haywo0d, A.M. (1994)J. Virol. 68, 1-5
Events
Of genes and germs
Michel Brahic and Jean-Francois Bureau
T
he apparent resurgence of in-
fectious diseases during the
past 20 years coincides with
spectacular advances in human gen-
etics that make it possible to locate
and identify genes involved in com-
mon multifactorial diseases. Conse-
quently, the role of the host genetic
background in the susceptibility to
infectious diseases can now be re-
examined with new tools. The recent
meeting held at the Pasteur Insti-
tute to cover this topic was indeed
timely.
Identification of a genetic com-
ponent in a disease can be diffi-
cult, as discussed by Alain Dessein
(INSERM, Marseilles, France). In
an area of Brazil that is endemic
for schistosomiasis, a detailed epi-
demiological study showed that en-
vironmental factors explained only
20% of the variance in parasite load.
Laurent Abel (INSERM, Paris,
France) showed that a single locus
with co-dominant transmission was
involved. To do this, he had to per-
form a segregation analysis with
corrections for environmental fac-
tors. A complete genome scan, car-
ried out on DNA from 20 families,
linked the level of infestation to a
region on chromosome 5 that codes
for CSF-1R (colony-stimulating
The First Louis Pasteur
Conference: Genetics of the
Susceptibility to Infectious
Diseases, Institut Pasteur, Paris,
France, 21-23 October 1996.
M. Brahic * and J-F. Bureau are in the
Unite des Virus Lents, URA CNRS 1157,
Institut Pasteur, 75724 Paris Cedex 15,
France. *tel: ÷33 1 45 68 87 70,
fax: +33 1 40 61 31 67,
e-mail: mbrahic@pasteur.fr
factor 1 receptor) and interleukins
3, 4, 5, 9 and 13. Interestingly, these
are cytokines implicated in the Th2-
type responses.
As discussed by Mark Lathrop
(University of Oxford, UK), this type
of parametric method is efficient
for locating a gene that has a major
effect. However, it requires making
assumptions, in particular on the
mode of inheritance. In contrast,
nonparametric methods, such as
sib pair analysis, are well suited to
the analysis of multigenic diseases,
although they require the collection
of data from many families. Finally,
testing candidate genes with a non-
parametric method can also yield
important information. Abel illus-
trated this point with a study of
leprosy and the occurrence of the
NRAMP1 gene (see below).
Copyright © 1997 Elsevier Science Ltd. All rights reserved. 0966 842X/97/$17.00
Mapping the genomes of mouse
and man
Genetic, physical and now 'inte-
grated' maps are the tools for these
studies and are constantly being re-
fined. Approximately 6000 micro-
satellite markers have been located
on the genetic maps of mouse
(William Dietrich, Harvard Uni-
versity, Boston, MA, USA) and hu-
man (Jean Weissenbach, Institut
Pasteur, Paris and Genethon, Evry,
France). The construction of physi-
cal maps, by ordering the markers
on overlapping yeast and bacterial
artificial chromosomes or by using
whole genome radiation hybrids, is
advancing rapidly. Integrated maps,
which give the position of individ-
ual mRNA on the genetic and physi-
cal maps, are the latest addition to
this field. Approximately 16000
expressed sequence tags have been
located on an integrated map of the
human genome by a consortium of
five groups. How these maps can
be used to arrive at the gene was
nicely illustrated by the work of
Dietrich on the susceptibility of the
A/J mouse to Legionella pneumo-
phila. The causal gene (Ignl) was
mapped to a small fraction of
chromosome 13, which happened
to be homologous to the region of
PlI: S0966-842X(96)30041-3
TRENDS IN MJCROBIOI.OC;y 48 vo~ 5 IN(). 2 FEBRtlARY 1997