NDLI: Fine mapping of the Bmgr5 quantitative trait locus for allogeneic bone marrow engraftment in mice

Content Provider	Springer Nature Link
Author	Wang, Yuanyuan Chen, Xinjian Tsai, Schickwann Thomas, Alun Shizuru, Judith A. Cao, Thai M.
Copyright Year	2013
Abstract	To identify novel mechanisms regulating allogeneic hematopoietic cell engraftment, we used forward genetics and previously described identification, in mice, of a bone marrow (BM) engraftment quantitative trait locus (QTL), termed Bmgr5. This QTL confers dominant and large allele effects for engraftment susceptibility. It was localized to chromosome 16 by quantitative genetic techniques in a segregating backcross bred from susceptible BALB.K and resistant B10.BR mice. We now report verification of the Bmgr5 QTL using reciprocal chromosome 16 consomic strains. The BM engraftment phenotype in these consomic mice shows that Bmgr5 susceptibility alleles are not only sufficient but also indispensable for conferring permissiveness for allogeneic BM engraftment. Using panels of congenic mice, we resolved the Bmgr5 QTL into two separate subloci, termed Bmgr5a (Chr16:14.6–15.8 Mb) and Bmgr5b (Chr16:15.8–17.6 Mb), each conferring permissiveness for the engraftment phenotype and both fine mapped to an interval amenable to positional cloning. Candidate Bmgr5 genes were then prioritized using whole exome DNA sequencing and microarray gene expression data. Further studies are warranted to elucidate the genetic interaction between the Bmgr5a and Bmgr5b QTL and identify causative genes and underlying gene variants. This may lead to new approaches for overcoming the problem of graft rejection in clinical hematopoietic cell transplantation.
Starting Page	585
Ending Page	596
Page Count	12
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	65
Issue Number	8
e-ISSN	14321211
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2013-05-12
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Bone marrow Engraftment Quantitative trait Locus Consomic mouse Congenic mouse Immunology Human Genetics Gene Function Cell Biology Allergology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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