Pbrbc4^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Pbrbc4^C57BL/6J
• Name: peripheral blood RBC 4; C57BL/6J
• MGI ID: MGI:3699869
• QTL: Pbrbc4 Location: unknown Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased peripheral blood RBC count compared to A/J. (J:118313)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:118313

Linkage analysis was performed on 361 (CBA/HOla x C57BL/6Ola)F2 intercross animals to identify QTLs associated with bone marrow and peripheral blood erythroid cell count. Genome scan was performed at a resolution of 10 cM - 15 cM using 133 polymorphic markers. Parental strain CBA/HOla displays increased bone marrow erythroid cell counts compared to parental strain C57BL/6Ola.

On mouse Chromosome 4, linkage to peripheral blood red blood cell (RBC) count was detected at 41.9 cM (84 Mb) with LOD=4. This locus is named Pbrbc1 (peripheral blood RBC 1). The 1-LOD support interval spans 32.2 cM - 48.2 cM (63 Mb - 98 Mb). CBA/HOla-derived alleles at Pbrbc1 confer increased peripheral blood RBC count with recessive inheritance.

Pbrbc1 was replicated and confirmed by analysis of 29 AXB/BXA recombinant inbred (RI) strains (LOD=7.5 at 40 cM). C57BL/6J-derived alleles at Pbrbc1 confer increased peripheral blood RBC in the AXB/BXA population.

10.21.2015 Curator Note: Because Pbrbc1 was originally mapped here using an (CBA/HOla x C57BL/6Ola)F2 intercross, which is a different mapping population then the 29 AXB/BXA recombinant inbred (RI) strains, we consider the RI panel a separate mapping study and have named the QTL indentifed (LOD=7.5 at 40 cM) using it as Pbrbc4.

Additional linkages to peripheral blood RBC count were detected in AXB/BXARI panel. Pbrbc2 (peripheral blood RBC 2) mapped to 58.5 cM on mouse Chromosome 1 (LOD=4.9). A/J-derived alleles at Pbrbc2 confer increased peripheral blood RBC count. The 1-LOD support interval spans 56 cM -59.5 cM. A potential candidate gene for Pbrbc2is Twist2. Pbrbc3 mapped to 59.9 cM on mouse Chromosome 16 (LOD=6). The 1-LOD support interval spans 57 cM - 66 cM (84.9 Mb - 92.3 Mb). C57BL/6J-derived alleles at Pbrbc3 conferincreased peripheral blood RBCcount. Ifnar1 at 63.2 cM is a potentialcandidate gene for Pbrbc3.

Significant linkage to erythroid/non-erythroid (E/NE) bone marrow cell ratio mapped to 78 cM on mouse Chromosome 5 (LOD=4.5). This locus is named Bmrbc1 (bone marrow RBC 1). C57BL/6Ola-derived alleles at Bmrbc1 confer increased bone marrow RBC count. The 1-LOD support interval spans 75 cM - telomere (124 Mb - 150 Mb). A potential candidate gene for Bmrbc1 is Epo at 78 cM. Sequence analysis did not detect polymorphism between CBA/HOla and C57BL/6Ola in the Epo promoter or coding and non-coding regions. Southern blot analysis of Epo did not detect copy number variations between CBA/HOla and C57BL/6Ola. A separate male-specific locus for E/NE bone marrow cell ratio mapped to 57 cM with LOD=3.5.

Female-specific linkage to E/NE ratio mappedto30cM on mouse Chromosome 11 (LOD=4.4). This locus is named Bmrbc2 (bone marrow RBC 2). The 1-LOD support interval spans 25 cM - 32 cM (49 Mb - 59 Mb). CBA/HOla-derived alleles at Bmrbc2 confer increased bone marrow RBC count in females with dominantinheritance.

Reanalysisof the data using sex as a covariate revealed a significant locus at 42 cM on mouse Chromosome 19 (LOD=4.3). This locus is named Bmrbc3 (bone marrow RBC 3). The 1-LOD support interval spans 31 cM - telomere (32 Mb - 61 Mb).C57BL/6Ola-derived alleles at Bmrbc3 confer increased red blood cell count with dominant inheritance. Pten at 24.5 cM is a potential candidate gene for Bmrbc3.

On mouse Chromosome X, linkage to E/NE ratio mapped to65 cM with LOD=6.3. This locus isnamed Bmrbc4(bone marrow RBC 4). CBA/HOla-derived alleles at Bmrbc4 confer increased bone marrow red blood cell count with recessive inheritance. The 1-LOD support interval spans 65 cM - telomere (147 Mb - 164 Mb). Bmrbc4 also exhibits suggestive linkage to peripheral RBC count with LOD=3.3 at 69 cM. C57BL/6Ola-derived alleles at Bmrbc4 confer increased peripheral RBC count with dominant inheritance.

Suggestive linkage to E/NE ratio mapped to 14 cM - 43 cM on mouse Chromosome 10, 47 cM on mouse Chromosome 15, and 0 cM - 27 cM on mouse Chromosome X. Suggestive linkage to E/NE ratio in males mapped to 0cM- 24 cMon mouse Chromosome 9. Suggestive linkage to spleen weight mapped to 27 cM - 44cM on mouse Chromosome 3 (LOD=3), 20 cM - 38 cM on mouse Chromosome 15 (LOD=3.1), and 15 cM - 34 cM on mouse Chromosome 17 (LOD=3.5).

References

• Original: J:118313 Jawad M, et al., Mouse bone marrow and peripheral blood erythroid cell counts are regulated by different autosomal genetic loci. Blood Cells Mol Dis. 2007 Mar-Apr;38(2):69-77
• All: 1 reference(s)