Bpq22^NZO/HlLtJ
QTL Variant Detail

Summary

• QTL variant: Bpq22^NZO/HlLtJ
• Name: blood pressure QTL 22; NZO/HlLtJ
• MGI ID: MGI:3758807
• QTL: Bpq22 Location: unknown Genetic Position: Chr4, cM position of peak correlated region/allele: 5.2 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NZO/HlLtJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele interacts with Bpq21 on chromosome 4 to decrease blood pressure. This allele interacts with Bpq23 on chromosome 8 to increase blood pressure. (J:125335)

Notes

Bpq22 interacts with Bpq21 on chromosome 1 and Bpq23 on chromosome 8. Animals with at least one C3H/HeJJcl allele at Bpq21 and homozygous for NZO/HILtJ alleles at Bpq22 exhibit decreased blood pressure. Animals homozygous for NZO/HILtJ alleles at Bpq22 and Bpq23 exhibit increased blood pressure.

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

J:125335

Linkage analysis was performed on 222 male F2 animals from reciprocal intercrosses between NZO/HlLtJ and C3H/HeJJcl to identify genetic loci associated with blood pressure. Parental strain NZO/HlLtJ displays high blood pressure, obesity, diabetes, and dyslipidemia whereas parental strain C3H/HeJJcl is lean and displays low blood pressure. Male animals were phenotyped at 10 weeks of age, and 92 polymorphic markers at an average spacing of 18.1 cM were used for the genome scan. Diastolic and systolic tail cuff blood pressure were analyzed individually and combined (as the first principal component PC1).

When systolic and diastolic blood pressures were analyzed separately, several suggestive loci were detected. Suggestive linkage to systolic blood pressure mapped to 43 cM on mouse Chromosome 3 near D3Mit29 and 61.5 cM on mouse Chromosome 8 near D8Mit49. Suggestive linkage to diastolic blood pressure mapped to 100 cM on mouse Chromosome 1 near D1Mit137, 57 cM on mouse Chromosome 3 near rs3687177, and 38.5 cM on mouse Chromosome 8 near D8Mit28.

When systolic and diastolic blood pressures were analyzed as the first principal component, three interacting loci on chromosomes 1 (Bpq21), 4 (Bpq22), and 8 (Bpq23) were detected with chromosome 4 at the center of the network. Two of these loci appeared as suggestive linkages in the individual component analysis. The interactions account for 29.4% of the blood pressure variance.

Bpq21 (blood pressure QTL 21) mapped to 100 cM on mouse Chromosome 1 near D1Mit36 (LOD=3.3). This locus explains 12.5% of the variance. C3H/HeJJcl-derived alleles at Bpq21 have an additive single-locus effect on decreasing blood pressure. Homozygosity for C3H/HeJJcl-derived alleles at Bpq21 in conjunction with C3H/HeJJcl homozygous alleles at Bpq22 (chr 4) confers significantly decreased blood pressure. At least 1 C3H/HeJJcl-derived allele at Bpq21 in conjunction with a homozygous NZO/HlLtJ genotype at Bpq22 also decreases blood pressure. Previously identified QTLs Obq9 (88.4 cM), Bpq2 (81.6 cM), and Bpq8 (80 cM) map near Bpq21. Abbp1 (36 cM) and Bpq1 (49.7 cM) also map to chromosome 1 but are more proximally situated. Potential candidate genes include Ren1 (69.9 cM), Ren2 (69.9 cM), Atp1a2 (94.2 cM), Ptpn14 (103.1 cM), and Kcnk2. Bpq21 is homologous to a region on human Chromosome 1q where two hypertension QTLs have been mapped by Mansfield et al (1997) and Ciullo et al (2006).

Bpq22 (blood pressure QTL 22) mapped to 6 cM on mouse Chromosome 4 near D4Mit261 (LOD=3.1). This locus explains 22.2% of the variance and interacts with Bpq21 and Bpq23. Previously identified diabetes QTLs Nidds (55 cM) and Nidd1 (48 cM) also map to chromosome 4. Homozygosity for NZO/HlLt-derived alleles at Bpq22 have a single-locus effect in decreasing blood pressure. Abbp2 (33 cM) and Bpq3 (28.6 cM) are previously identified QTLs mapping near Bpq22. The Bpq22 interval is homologous to a region on human Chromosome 8q22-q23 where a hypertension QTL was identified by Ciullo et al (2006).

Bpq23 (blood pressure QTL 23) mapped to 29 cM on mouse Chromosome 8 near D8Mit28 (LOD=4.3). This locus explains 12% of the variance. C3H/HeJJcl-derived alleles at Bpq23 have a single-locus additive effect of decreasing blood pressure. This locus also interacts with Bpq22 on chromosome 4. Homozygosity for NZO/HlLtJ-derived alleles at both Bpq23 and Bpq22 confers increased blood pressure. However, the presence of at least one C3H/HeJJcl-derived allele at Bpq23 in conjunction with a homozygous NZO/HlLtJ genotype at Bpq22 decreases blood pressure. Potential candidate genes include Klkb1 (26 cM) and Lpl (33 cM). Several human hypertensions QTLs have been mapped to chromosome 8p21, chromosome 16, and chromosome 19p12-p13. These human regions are homologous to the Bpq23 interval.

**Note: Authors' original symbol designations were Bpq10 (chr1), Bpq11 (ch4), and Bpq12 (chr8). These symbols were previously reserved by a different author so new symbols Bpq21, Bpq22, and Bpq23 were assigned, respectively.

References

• Original: J:125335 Nishihara E, et al., Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ x C3H/HeJ intercrosses. Mamm Genome. 2007 Aug;18(8):573-83
• All: 1 reference(s)