Comment[ArrayExpressAccession] E-GEOD-43377 MAGE-TAB Version 1.1 Public Release Date 2013-01-10 Investigation Title Mouse Diversity Array SNP Genotyping of B10.BALBChr16 and BALB.B10Chr16 Reciprocal Consomic Strain Mice Comment[Submitted Name] Mouse Diversity Array SNP Genotyping of B10.BALBChr16 and BALB.B10Chr16 Reciprocal Consomic Strain Mice Experiment Description To identify novel mechanisms regulating allogeneic hematopoietic cell engraftment, we previously used a forward genetic approach and described identification, in mice, of the Bmgr5 bone marrow (BM) engraftment quantitative trait locus (QTL). This QTL confers dominant and large allele effects for engraftment susceptibility. It was localized to chromosome 16 by classical 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 and Bmgr5b, 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 profiling. Further studies are needed to elucidate the genetic interaction between Bmgr5a and Bmgr5b 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. B10.BALBChr16 and BALB.B10Chr16 consomic strain mice were constructed in our laboratory for validation of bone marrow engraftment and graft-vs-host diseaes QTLs. The parental strains for consomic line construction were B10.BR (B10.BR-H2k H2-T18a/SgSnJJrep) and BALB.K (C.C3-H2k/LilMcdJ). The JAX Mouse Diveristy 620K SNP Array was used to verify adequate removal of residual background heterozygosity. Liver DNA was delivered to JAX Mouse Diversity Genotyping Array Service (Jackson Laboratory) for the SNP Array genotyping. Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name Cao Cao Person First Name Thai Thai Person Mid Initials M Person Email thai.cao@hsc.utah.edu Person Affiliation University of Utah Person Address University of Utah, 30 North 1900 East, SOM5C402, Salt Lake City, UT, USA Person Roles submitter Protocol Name P-GSE43377-1 P-GSE43377-6 P-GSE43377-3 P-GSE43377-8 P-GSE43377-7 P-GSE43377-2 P-GSE43377-4 P-GSE43377-5 Protocol Description ID_REF = VALUE = Genotype Call (SNP call): AA, AB, BB, NC (NoCall). DNA was restriction digested, PCR amplified, fragmented, labeled and hybridized to each array according to the manufacturer's instructions. DNA was extracted from liver of consomic mice maintained in our breeding colony at the University of Utah. CEL files were analyzed using R MouseDivGeno software by the JAX Mouse Diversity Genotyping Array Service (Jackson Laboratory). The arrays were scanned using an Affymetrix GeneChip Scanner 3000. None DNA was extracted from proteinase-K digested liver DNA using DNeasy Tissue Kit (Qiagen). As per manufacturer (Affymetrix) Protocol Type bioassay_data_transformation hybridization grow feature_extraction image_aquisition specified_biomaterial_action nucleic_acid_extraction labeling Experimental Factor Name PARENTAL STRAIN CONSOMIC LINE Experimental Factor Type parental strain consomic line Comment[SecondaryAccession] GSE43377 Comment[GEOReleaseDate] 2013-01-10 Comment[ArrayExpressSubmissionDate] 2013-01-09 Comment[GEOLastUpdateDate] 2013-01-12 Comment[AEExperimentType] comparative genomic hybridization by array SDRF File E-GEOD-43377.sdrf.txt