Announce: EUCIB WWW pages

Mr. R. Williams rwilliaa at hgmp.mrc.ac.uk
Wed Dec 21 05:38:29 EST 1994


The UK Human Genome Mapping Project Resource Centre announces its
WWW pages for the 

European Collaborative Interspecific Mouse BackCross

You can access these pages from

http://www.hgmp.mrc.ac.uk/local-data/mbx/Mbx_Homepage.html


These pages work best with mosaic or netscape.  The Genetic Maps do
not display using lynx.

A Facility for Mapping the Mouse Genome 

 The Mouse Genome 

The mouse is a primary model organism for the Human Genome Project and
considerable emphasis has been placed on the genetic and physical
mapping of the mouse genome worldwide. Comparison of the genetic maps
of mouse and human indicate a large number of chromosome regions where
the genetic order is conserved. These conserved linkage groups enable
us to identify mouse genetic loci which may be homologous to human
mutations that cause genetic disease often providing powerful animal
models for the disease process. In addition, the ability in the mouse
to target new mutations to genes that may be involved in human genetic
disease has opened up vital avenues for the exploration of mammalian
gene function.

 The European Collaborative Interspecific Backcross 

In order to expedite these areas, the mouse genome project has set as
one of its primary goals the development of a high resolution (<1cM)
genetic map that will form the basis for the construction of a complete
physical map of the mouse genome. In Europe, we have begun a European
Collaborative project - the European Collaborative Interspecific
Backcross (EUCIB) to provide the resources for the high resolution
genetic mapping of the mouse genome. This project is being carried out
at two centres - the Human Genome Mapping Project (HGMP) Resource
Centre, UK and the Pasteur Institute, France.

A 1,000 animal interspecific backcross between C57BL/6 and Mus spretus
has been completed and DNAs prepared. Each backcross progeny mouse has
been scored for 3-4 markers per chromosome completing an anchor map of
70 loci across the mouse genome. A 1,000 animal cross provides a
genetic resolution of 0.3cM with 95% confidence. Completion of the
anchor map allows the identification of pools of animals recombinant in
individual chromosome regions and allows a rapid two-stage hierarchical
mapping of new loci. New markers are first analysed through a panel of
40-50 mice in order to identify linkage to a chromosome region.
Subsequently, the new marker is analysed through a panel of mice
identified as carrying recombinants within that chromosome region.

 The MBx database. 

The backcross is supported by a new database - MBx - developed in
SYBASE. MBx stores mouse, locus and probe data. It stores all allele
data at each chromosome locus for each of the 1,000 backcross progeny.
Allele data is presented as a scrollable matrix on screen. When a new
marker is analysed through the backcross, MBx provides lod score
information to indicate linkage to a chromosome region. Using the
computer screen, recombinant mice in this chromosome region can be
selected for the second stage of heirarchical screening. In addition,
at each stage, MBx will not only calculate the available lod scores for
closely linked markers but will also determine genetic order with
respect to closely linked markers by minimising the number of
recombinants.


 EUCIB in action 


EUCIB is a platform for a variety of programmes directed towards the
construction of complete genetic and physical maps of the mouse
genome.  

A genetic mapping service for the mouse genome

A dedicated user service is provided from the UK HGMP Resource Centre
for assignment of both mouse and human probes on the genetic map of the
mouse. Filters, or small amounts of DNA for PCR, representing upto 50
random backcross progeny are issued on request and allow detection of
linkage to anchor markers and assignment of probes to a particular
chromosome interval.  Further DNAs from backcross progeny mice
recombinant in the relevant genetic interval can be provided for more
detailed mapping.

A high resolution microsatellite map of the mouse - towards STS
YAC contiging of the mouse genome

In collaboration with the MIT Genome Centre, US (Dr Eric Lander), the
UK Resource Centre is embarking upon a major three year programme to
map 3,000 micro satellites on the European Backcross. A similiar number
will be mapped in the US using DNAs provided from EUCIB.
Microsatellites generated at the MIT Genome Centre are already assigned
in a smaller mouse cross to individual chromosome regions and are then
being mapped through the relevant backcross progeny from EUCIB that are
recombinant in the appropriate interval. The high genetic resolution
(0.3cM) provided by the size of the European Backcross will allow the
creation of a detailed, ordered STS map of the mouse genome that will
strongly underpin efforts towards the complete STS YAC contiging of the
mouse genome.

Mapping IRS-PCR products on the mouse genome

Dr Hans Lehrach, ICRF, UK has instituted a programme of research with
EUCIB that involves the fine genetic mapping of a large number of
random mouse IRS-PCR products. In additoin, each mapped IRS-PCR product
is being screened against two UK mouse YAC libraries (from St Mary's,
London and ICRF, London) in porder to integrate the genetic map with
the growing physical map.

In summary, EUCIB provides an international resource for the high
resolution genetic mapping of the whole mouse genome as a prelude to
physical mapping using an STS based YAC contig approach.

Steve Brown  
St Mary's Hospital Medical School, London


<A HREF = "http://www.hgmp.mrc.ac.uk/local-data/mbx/Mbx_Homepage.html">
EUCIB home-page</A>










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