Comparative
radiation hybrid mapping
Development
of a bovine whole genome radiation hybrid map for comparative
mapping across species and the identification of positional
candidate genes for genetically mapped traits.
This
work is supported by the European
Union (Project CT BIO 98 - 0277).
Data
from
Williams et al (2002)
A Bovine Whole Genome Radiation Hybrid Panel and
Outline Map. Mammalian Genome 13 469-474.
The
primary objective of this work is to provide the tools
to efficiently identify candidate genes for disease
and quantitative traits in cattle, by directly mapping
a large number of bovine expressed sequences, and indirectly
through building comparative mapping links to identify
comparative positional candidate genes.
Positional
candidate gene cloning is currently the most successful
method of identifying trait genes. This project will
establish a high resolution whole genome radiation hybrid
(WGRH) map in cattle and, through the map, build high
resolution comparative mapping links with maps in other
species - man and mouse.
Microsatellite
loci will be used to characterise a bovine WGRH panel
and create a framework map which will align the radiation
hybrid map with the bovine genetic map. It will then
be possible to relate quantitative trait and disease
gene mapping studies directly to the radiation hybrid
map. A large number of genes and expressed sequence
tagged sites (ESTS) will be placed on the radiation
hybrid map, providing a large number of candidate genes
as a resource for positional cloning of trait genes.
The mapped ESTS will allow alignment of the physical
and genetic maps between species. High resolution comparative
mapping links between the bovine map and the very high
density maps in human and mouse will be important to
the identification of trait genes though comparative
positional candidate cloning.
The
bovine ESTS to be mapped will be generated from bovine
gene sequences present in sequence databases, cDNA sequenced
as part of this project, from mapped human ESTS and
from exons identified in the vicinity of bovine microsatellite
loci. Confirmed homologies between the bovine ESTS and
those which appear on human and murine maps will enable
high resolution alignment of maps across species.
There
are four strategies for developing the bovine ESTS and
will be fully developed and implemented here:
