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Most biological traits of adaptive significance, and
the most common diseases, from a genetic point of view, are complex, quantitative
phenotypes. In spite of intensive efforts, the genetic control of complex
traits are not well understood because traditional human genetic studies
could not overcome the difficulties presented by genetic heterogeneity,
polygenic effects and interactions, uncontrollable developmental-environmental
variability, etc.
The striking genomic similarity between humans and laboratory animal
species (99% of the genes in humans have their counterparts in the
mouse) is encouraging for using animal models to analyze complex
traits. The Recombinant Quantitative Trait Locus Introgression (RQI)
strain system was established to circumvent some of the above described
difficulties, to facilitate mapping of Quantitative Trait Loci (QTLs),
and to generate advanced quasi-congenic animal models.
B6vsC.pbase: a phenotype database
C57BL/6 and BALB/c are among the most often used inbred mouse strains.
B6vsC.pbase is an ever growing collection of published complex trait
differences between the two progenitor strains of the RQI strain
set.
RQI.gbase: a genotype database
Genome scanning with about 350 microsatellite markers provided information
about the distribution of BALB/c donor chromosome segments on C57BL/6
background in 100+ RQI strains. Genotyping to further increase the
resolution of the genome scan is still in progress.
How to use the databases
The B6vsC.pbase and RQI.gbase datasets can be used in an
interactive manner or individually. The possible uses include the
following.
- If
there is a B6vsC complex trait difference, phenotypic screening of RQI
strains may identify quasi-congenic strains which significantly differ
from the background partner C57BL/6 strain.
- If
a QTL have been mapped in a C57BL/6 X BALB/c cross derived population,
a search can identify a quasi-congenic strain with a BALB/c chromosome
segment which harbors the mapped QTL. If the mapping results can be
verified one can quickly proceed towards “positional cloning”.
- Haplotype
pattern information on C57BL/6 and BALB/c is available in a haplotype
pattern database, SNPview (www.gnf.org/SNP).
After identifying a QTL harboring chromosome segment in an RQI strain
it may no longer be necessary to initiate difficult high resolution
mapping of a QTL. Comparison of SNPview with RQI.gbase can identify
nonshared haplotypes which underlie phenotypic traits including disease
susceptibility. This approach can reduce QTL intervals to sizes amenable
to “positional cloning”.
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