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

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC3713196 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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

Wang Yuanyuan Y Chen Xinjian X Tsai Schickwann S Thomas Alun A Shizuru Judith A JA Cao Thai M TM

Immunogenetics 20130512 8

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 ...[more]

PMID: 23666360

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Project description:Background:Grain weight is a grain yield component, which is an integrated index of grain length, width and thickness. They are controlled by a large number of quantitative trait loci (QTLs). Besides major QTLs, minor QTLs play an essential role. In our previous studies, QTL analysis for grain length and width was performed using a recombinant inbred line population derived from rice cross TQ/IRBB lines. Two major QTLs were detected, which were located in proximity to GS3 and GW5 that have been cloned. In the present study, QTLs for grain weight and shape were identified using rice populations that were homozygous at GS3 and GW5. Method:Nine populations derived from the indica rice cross TQ/IRBB52 were used. An F10:11population named W1, consisting of 250 families and covering 16 segregating regions, was developed from one residual heterozygote (RH) in the F7generation of Teqing/IRBB52. Three near isogenic line (NIL)-F2 populations, ZH1, ZH2 and ZH3 that comprised 205, 239 and 234 plants, respectively, were derived from three RHs in F10:11. They segregated the target QTL region in an isogenic background. Two NIL populations, HY2 and HY3, were respectively produced from homozygous progeny of the ZH2 and ZH3 populations. Three other NIL-F2 populations, Z1, Z2 and Z3, were established using three RHs having smaller heterozygous segments. QTL analysis for 1000-grain weight (TGW), grain length (GL), grain width (GW), and length/width ratio (LWR) was conducted using QTL IciMapping and SAS procedure with GLM model. Result:A total of 27 QTLs distributed on 12 chromosomes were identified. One QTL cluster, qTGW2/qGL2/qGW2 located in the terminal region of chromosome 2, were selected for further analysis. Two linked QTLs were separated in region Tw31911-RM266. qGL2 was located in Tw31911-Tw32437 and mainly controlled GL and GW. The effects were larger on GL than on GW and the allelic directions were opposite. qTGW2 was located in Tw35293-RM266 and affected TGW, GL and GW with the same allelic direction. Finally, qTGW2 was delimited within a 103-kb region flanked by Tw35293 and Tw35395. Conclusion:qTGW2 with significant effects on TGW, GL and GW was validated and fine-mapped using NIL and NIL-F2 populations. These results provide a basis for map-based cloning of qTGW2 and utilization of qTGW2 in the breeding of high-yielding rice varieties.

Dataset Information

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

Publications

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

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