Meeting Report: 15
International Mouse Genome Conference
Deborah E. Cabin,
Lisa E. Olson,
Roger H. Reeves
National Human Genome Research Institute, National Institutes of Health, Bldg. 49, Rm. 4B67, 49 Convent Dr., Bethesda, Maryland 20892, USA
Department of Physiology, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, Maryland 21205, USA
Received: 26 November 2001 / Accepted: 3 January 2002
Mouse Genome Conference was held October 21–24 in
Edinburgh, Scotland, organized by Ian Jackson. The Conference
traditionally starts with the Verne Chapman Memorial Lecture.
This year’s lecture, “Wild Mice as a Source of Genetic Polymor-
phism,” was presented by Prof. Jean-Louis Gue´net (Institut Pas-
teur). He discussed several ways in which polymorphism in wild
strains contributes to basic research. First and perhaps best known
are the benefits derived in construction of genetic maps. Because
most laboratory strains of mice were derived relatively recently
from a small founder population, consisting mostly of mice from
the Mus musculus subspecies complex, the genetic diversity is low.
For example, nearly all laboratory strains carry a Y chromosome
from M.m musculus. The use of lines derived from wild mice such
as Mus spretus introduces a degree of polymorphism that allows
the generation of high-resolution genetic maps that are invaluable
for positional cloning and as scaffolds for physical maps, leading
to genomic sequencing.
The genetic diversity in wild mice is reflected in many traits
that differ from those exhibited by common laboratory inbred
strains. While all Mus species are similar in morphology, their
behavior varies substantially. Numerous examples of the use of
Mus spretus in mapping a variety of phenotypes were discussed
during the meeting. Prof. Gue´net discussed inter-species differ-
ences in viral resistance in wild mice as well as the wealth of major
histocompatability and Ig alloform differences. Inter-specific
crosses are a fertile area for studying epistatic interactions that
influence traits such as hybrid sterility, obesity, and tumor forma-
tion. Cytological variations found in wild populations, for ex-
ample, Robertsonian translocations recovered from some popula-
tions of the Mus musculus domesticus species, such as those mice
living in the Poshiavo Valley of Switzerland, which are often
designated Mus poschiavinus, have also been extremely useful in
studying imprinting. Dr. Gue´net predicts that there will be a great
future for the use of wild mice in functional genomic studies, for
instance in drug resistance studies, mitochondrial studies using
conplastic strains (congenic lines in which the mitochondria are
derived from a different founder by continued backcrossing to
females of a hybrid carrying the mitochondria to be introgressed),
and parasitology studies including parasitic load and the genetic
course of response to natural infections. The identification and
analysis of DNA regulatory elements between mouse species is of
great interest, as the evolutionary distance between M.m. musculus
and M. spretus (2 to 3 Myr) is approximately the same as that
between man and chimpanzee (5.5 Myr).
The meeting opened officially with a session on Genome Se-
quencing and Comparative Analysis. The plenary talk by John
McPherson (Washington University, St. Louis) reported on the
status of the Washington University mouse genome sequencing
project. Along with the sequencing efforts at the Whitehead Insti-
tute (presented by Kerstin Lindblad-Toh), it appears that an as-
sembly of the eagerly awaited, publicly accessible sequence at
5–6× draft coverage will be available by February–March. The
mouse sequence is largely clone-based, though the initial assembly
(available at http://ncbi.nlm.nih.gov/Traces) is derived mostly
from ∼2–3× draft, whole-genome shotgun sequencing at White-
head. The Whitehead sequence coverage is in 650,000 contigs, the
majority (86%) of which are anchored and average about 4.8 kb.
These trace sequences provided about 2.7× coverage as of Sept.
2001 and are being aligned against the human sequence. This
alignment is ongoing, both to help annotate the human sequence
and, along with BAC end sequences, to anchor the mouse BAC
map. A shotgun assembly of these sequences will also be per-
formed. Early analysis of the current sequence suggests that mouse
is about 41% GC, with about 1.5% coding sequences, and another
1.5% non-coding but conserved with human. Repeat content is
about 40%, and the human has about 15% more repeats.
Members of the public sequencing consortium are currently
using 305,000 BAC clones, of which 295,000 are now in contigs.
BAC fingerprint data will be accessible at: http://www.bcgsc.bc.
ca/projects/mouse mapping/. Washington U. has 711 BAC contigs,
Sanger 539, and these can be viewed or downloaded (see http://
genome.wustl.edu/gsc/mouse/ and http://mouse.ensembl.org/).
The Washington U. contigs cover an average 5 Mb each and total
about 2.8 Gb, or 93% of the mouse genome. It is expected that the
assembled mouse genome will be available in early 2003, with
about 3 gaps/100 kb, and the finished sequence will be ready by
the end of 2005 with about 1 error per 10,000 bases. The sequenc-
ing centers are collaborating on an assembly, apparently in parallel
with their in-house assembly and annotations, and currently plan to
incorporate genomic sequence, BAC contig structure, and BAC
end sequences (see below), accessible at http://mouse.ensembl.
org/. Sequencing progress can be followed via a newsletter that
also provides useful web links and is available at http://mouse.
ensembl.org/newsletter/. Shaying Zhoa reported on TIGR’s BAC
end sequencing project. This effort has produced a BAC end se-
quence on average every 7 kb across the genome, and these se-
quences are being aligned to human sequence. This not only pro-
vides a structure for mouse sequence assembly, but also serves as
an assessment of the different assemblies of the human draft se-
quence. Good progress is being made on the recently initiated rat
BAC end sequencing project, as well as BACs from a number of
primate species. See http://www.tigr.org/tdb/bac_ends/mouse/
bac_end_intro.html. The UK Mouse Sequencing Program (Ann
Marie Mallon, Harwell) is using a mapping and sequencing ap-
proach to focus on specific regions on MMU 2, 4, 13, and X. 5.2
Mb is finished, with an additional 22 Mb in the finishing stage.
These finished sequences are being annotated in ENSEMBL and
aligned with the human sequence.
The mouse genome sequence provides a second mammalian
genome with which to identify evolutionarily conserved regions,
Correspondence to: D.E. Cabin
© Springer-Verlag New York Inc. 2002Mammalian Genome 13, 229–233 (2002).
Incorporating Mouse Genome