Vpq1^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Vpq1^CAST/EiJ
• Name: vaginal patency QTL 1; CAST/EiJ
• MGI ID: MGI:5775030
• QTL: Vpq1 Location: unknown Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL

Notes

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

J:184775

To identify loci that regulate female sexual maturity, including loci that mediate lifespan tradeoffs, haplotype association mapping (HAM) for age of vaginal patency (VP) was performed.

Lifespan data on 31 inbred strains was previously published (J:216124). The previous lifespan data was updated to include data for 32 MOLF/EiJ females in the current study (Table S1). When the wild-derived strains were included, 3 significant QTLs for age of vaginal patency were identified, all p^{0.01, all mapped on (NCBI) build 37.}

Vpq1, vaginal patency QTL 1, mapped to Chr 4 between 62.69 and 62.76 Mb;

Vpq2, vaginal patency QTL 2, mapped to Chr 16 between 37.68 and 37.7 Mb; and

Vpq3, vaginal patency QTL 3, mapped to Chr 16 to 74.84 Mb. Nrip1 is a candidate gene for Vpq3.

ANOVA analysis showed that the haplotypes of these 3 loci accounted for 75.6% (p=0.0003) of the variation in age of VP. At each of the three loci, the four wild derived strains ( PWD/PhJ,WSB/EiJ, CAST/EiJ and MOLF/EiJ) share the same haplotype, which is different from those at the same location in domesticated inbred strains, with one exception, SM/J which has the same haplotypes as the wild-derived mice at Vpq1 and Vpq2. Analysis of allele effects showed that strains with the wild-derived alleles at all 3 QTL had a significantly later age of VP p<0.05) compared with strains with any other alleles at those loci. No significant QTL was identified when the wild-derived strains were excluded.

In support of the hypothesis that strains with lower Igf1 have significantly delayed age of female sexual maturation, measured by VP, and that among strains with normal lifespans a delayed age of VP associated with greater longevity, C57BL/6J mice were set up concurrently with congenic B6.C3H-Igf1 mice. B6.C3H-Igh1 mice carry a C3H allele (Chr10: 65-90 Mb) on the B6 background. This study confirmed that compared with B6.C3H-Igf1 mice, B6 mice have significantly (p<0.05) decreased Igf1 at 6 months of age, but only in females. The age of VP of B6 was significantly delayed compared with B6.C3H-Igh1 females (p<0.05) and the lifespan of B6 females was greater by 24%, p<0.0001 (Fig 2D&E Table S3).

For 27 of the 31 strains in the survey, body weight at 38 d could be obtained from the Mouse Phenome Database (MPD). Data for NOD, MRL, P, and PWD only were unavailble. Strains with lighter body weight have a delayed age of VP (Fig S1). For body weight at 38 d HAM analysis, including the wild-derived strains, detected four significant QTL, p<0.01.

Bwq15, body weight QTL 15, mapped to Chromosome 4 between 154.11 and 154.17 Mb;

Bwq16, body weight QTL 16, mapped to Chromosome 5 between 53.38 and 53.54 Mb;

Bwq17, body weight QTL 17, mapped to Chromosome 10 between 49.34-49.47 Mb;

and Bwq18, body weight QTL 18, mapped to Chromosome 16 between 82.27 and 82.58 Mb; all mapped on (NCBI) build 37.

No significant QTL were identified when the wild-derived strains were excluded, and the QTL for age of VP did not overlap with the QTL for body weight.

Consomic B6-Chr16 mice which carry Chr 16 of the wild derived strain PWB/PhJ on a B6 background had a significantly reduced Igf1 level (p<0.05) at 2 months of age and later age of VP when compared with B6 mice.

References

• Original: J:184775 Yuan R, et al., Genetic coregulation of age of female sexual maturation and lifespan through circulating IGF1 among inbred mouse strains. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8224-9
• All: 1 reference(s)