Bomd3^C57BL/6
QTL Variant Detail

Summary

• QTL variant: Bomd3^C57BL/6
• Name: bone mineral density 3; C57BL/6
• MGI ID: MGI:2178273
• QTL: Bomd3 Location: Chr2:80005954-80006113 bp Genetic Position: Chr2, cM position of peak correlated region/allele: 47.93 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased bone mineral density compared to DBA/2. (J:75820)
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:75820

18 BXD (B = C57BL/6, D = DBA/2) recombinant inbred (RI) strains were used to map QTLs associated with bone mineral density. Two sex-specific loci were identified on mouse Chromosome 2 and mouse Chromosome 7, and confirmed in a (C57BL/6 x DBA/2)F2 population. Bomd3 is a female specific locus mapping to Chromosome 2 near D2Mit94 at approximately 48 cM. DBA/2-derived alleles appear to confer increased bone mass in a dominant fashion at Bomd3. Bomd4 is a male specific locus and maps to Chromosome 7 near D7Mit114 at approximately 8 cM. DBA/2-derived alleles appear to confer increased bone mineral density in an additive or dominant fashion at Bomd4.

J:99373

Linkage analysis was performed on a population of (C57BL/6J x DBA/2J)F2 animals to confirm provisional QTL associated with bone mineral density (BMD) mapped in a previous study. A subset of phenotypically extreme F2 animals was genotyped for an initial genetic screen. Next, all 994 F2 animals were genotyped for markers flanking provisional QTL. All identified QTL were also confirmed using short-term selected lines by comparing allele frequencies at each identified locus in high BMD or low BMD lines. FourQTL accounting for 16% of the variance in peak whole body BMD were identified.

Bomd5 (bone mineral density 5) mapped to 101.5 cM on mouse Chromosome 1 near D1Mit291 (LOD=6.2). DBA/2J-derived alleles at Bomd5 confer increased whole body bone mineral density. Bmd1 (87.9 cM) is a previously identified bone density QTL mapping near Bomd5. The Bomd5 interval is syntenic to human Chromosome 1q21-q43.

Bomd3 (bone mineral density 3) mapped to 51.4 cM on mouse Chromosome 2 near D2Mit480. DBA/2J-derived alleles at Bomd3 confer increased whole body bone mineral density. Bomd3 occupies a broad interval so recombinant inbred strain analysis was used to localize the QTL. Recombinant inbred strain BXD-8 carries a recombination between D2Mit14 (C57BL/6J-derived) and D2Mit249 (DBA/2J-derived). Association between BMD and a marker (D2Mit94; LOD=11) proximal to the recombination point was observed in a (BXD-8 x DBA/2J)F2 intercross. This result narrows the Bomd3 region to a 9-10 cM interval around 48 cM. A potential candidate gene for Bomd3 is Ext2 at 51 cM. Sbmd2 (18 cM) is a previously identified bone density QTL mapping near Bomd3. The Bomd3 interval is syntenic to human Chromosome 2q21-q32 and human Chromosome 11p-q12.

Bomd6 (bone mineral density 6) mapped to 69.8 cM on mouse Chromosome 4 near D4Mit312 (LOD=12.3). DBA/2J-derived alleles at Bomd6 confer increased whole body bone mineral density. The Bomd6 interval is syntenic to human Chromosome 1p36.3-p34.1.

Bomd7 (bone mineral density 7) mapped to 52 cM on mouse Chromosome 11 near D11Mit179. This locus may contain 2 closely linked QTL. C57BL/6J-derived alleles at Bomd7 confer increased whole body bone mineral density. Bomd7 occupies a broad interval so recombinant inbred strain analysis was used to localize the QTL. Recombinant inbred strain BXD-8 carries a recombination between D11Mit355 (C57BL/6J-derived) and D11Mit179 (DBA/2J-derived). Association between BMD and a marker (D11Mit349; LOD=10.1) proximal to the recombination point was observed in a (BXD-8 x DBA/2J)F2 intercross. This result reduces the Bomd7 interval to a region around 32 cM containing several candidate genes. Sbmd4 (49 cM) is a previously identified bone density QTL mapping near Bomd7. The Bomd7 interval is syntenic to human Chromosome 5q31-q35and human Chromosome 17p13-q22.

References

• Original: J:75820 Orwoll ES, et al., Gender specificity in the genetic determinants of peak bone mass. J Bone Miner Res. 2001 Nov;16(11):1962-71
• All: 2 reference(s)