Introduction To RQI Genetics.
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
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. (click here to read more)
B6vsC.pbase: a phenotype database
C57BL/6J (B6) and BALB/cJ (C), and their various sublines, are among
the most often used inbred mouse strains. B6vsC.pbase is an ever growing
collection of published complex trait differences between B6, C, and their
sublines. The progenitor strains of the quasi-congenic RQI strain set include
C57BL/6By and BALB/cJ.
RQI.gbase: a genotype database
Genome scanning with 400 microsatellite markers provided information about
the distribution of BALB/cJ donor chromosome segments on C57BL/6By 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 complex trait difference between B6 and C, phenotypic screening
of RQI strains can identify quasi-congenic strains which significantly differ
from the background partner. Quasi-congenic strains can give rise to F2 and
backcross populations, in which genes segregate on a homogeneous genetic background.
The homogeneous genetic background results in lower genetic "noise" in the segregating
populations providing a powerful tool for high-resolution mapping and identification
of interactions. Also, with marker assisted selection a series of "subcongenics" can
be developed for rapid mapping and mechanism oriented work.
If a QTL has 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 with the RQI strains, one can quickly proceed towards "positional cloning".
SNP and haplotype pattern information on C57BL/6 and BALB/c is available, for
example, in dbSNP, www.ncbi.nlm.nih.gov/SNP,
Mouse Genome Informatics database, www.jax.org/phenome/,
and SNPview, www.gnf.org/SNP. After identifying a QTL
harboring chromosome segment in an RQI strain one can initiate high resolution
mapping of a QTL. Comparison of SNP distribution patterns with RQI.gbase may
identify nonshared regions which underlie phenotypic traits including disease
susceptibility. The B6.C RQI strains are of bilineal origin: This design feature
eliminates complications in mapping caused by segregation of multiple alleles on
heterogeneous genetic background derived from multiple progenitor strains.
The RQI approach in combination with the increasing availability of genomic
sequence data for C57BL/6 and BALB/c can reduce QTL intervals to sizes
amenable to "positional cloning".