Sbmd5^AKR/J
QTL Variant Detail

Summary

• QTL variant: Sbmd5^AKR/J
• Name: spinal bone mineral density 5; AKR/J
• MGI ID: MGI:3710668
• QTL: Sbmd5 Location: unknown Genetic Position: ChrX, Syntenic

Variant origin

• Strain of Specimen: AKR/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased post-maturity spinal bone mineral density compared to SAMP6. (J:120855)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Pmsbmd1 exhibits additive inheritance. This locus also shows suggestive linkage to global bone mineral density (BMD).

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

J:102750

Linkage analysis performed on animals from a (SAMP6 x AKR/J)F2 intercross mapped a QTL associated with spinal bone mineral density between 4 and 6 months of age to an interval on mouse Chromosome X between 145 Mb and 158 Mb (P=0.01). This locus is designated Sbmd5 (spinal bone mineral density 5).

Sbmd5 is sytenic to a 10.9 Mb region on proximal human Chromosome X. SNP analysis was performed on possible candidate genes found within the human syntenic region. Two SNPs located in intron 6 of the PIR gene showed association with bone mineral density in a cohort of 1053 women. Pir is located near the QTL peak and the center of the Sbmd5 interval in mouse.

J:120855

Genetic loci associated with post-maturity spinal bone mineral density (BMD) were mapped in two independent between(AKR/J x SAMP6)F2 intercrosses.

Two reciprocal crosses were set up between mouse strains AKR/J and SAMP6, pairing males of each strain individually with females of the other strain. The F1 hybrid progeny from each cross direction were randomly interbred, and their resulting progeny composed the independent F2 intercosses.

The first cross consisted of 253 F2 animals and the second cross consisted of 110 F2 animals. Microsatellite markers at an average spacing of 7 cM were used for the genome scan. Parental strain AKR/J displays continued increase in spinal BMD up to 8 months of age whereas parental strain SAMP6 plateaus at 4 months of age.F2 animals were scanned for spinal and global BMD at 4, 6, and 8 months of age.

Significant linkage to post-maturity spinal BMD (Sbmd5) was detected at 140 Mb - 155 Mb on mouse Chromosome X between DXMit197 and DXMit31. This locus explained 34% of the variance and reached LOD=5 in the larger F2 cross and LOD=5.8 in the smaller F2 cross. AKR/J-derived alleles at Sbmd5 confer increased post-maturity spinal BMD with and additive mode of inheritance. Sbmd5 is also shows suggestive linkage to global BMD. Interestingly, a locus on human Chromosome Xassociated with lumbar BMD in post-menopausal women maps near the 96% confidence interval of Sbmd5.

SNP mapping of AKR/J and SAMP6 strains revealed several stretches of non-polymorphic DNA on mouse Chromosomes X outside the Sbmd5 region, and also onmouse Chromosome 7. Authors surmise these synonymous genetic regions did not arise by chance.

Linkage to post-maturity spinal BMD was also detected on mouse Chromosome 7 with LOD=11.8 but only in the smaller F2 cross. This locus requires further verification.

References

• Original: J:102750 Parsons CA, et al., Interspecies synteny mapping identifies a quantitative trait locus for bone mineral density on human chromosome Xp22. Hum Mol Genet. 2005 Nov 1;14(21):3141-8
• All: 2 reference(s)