Tgq4^NZW/LacJ
QTL Variant Detail

Summary

• QTL variant: Tgq4^NZW/LacJ
• Name: triglyceride QTL 4; NZW/LacJ
• MGI ID: MGI:3812493
• QTL: Tgq4 Location: unknown Genetic Position: Chr7, Syntenic

Variant origin

• Strain of Specimen: NZW/LacJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased triglyceride levels compared to NZB/BlNJ. (J:138463)

Notes

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

J:138463

Genetic loci associated with plasma triglycerides, free fatty acids and glucose levels were mapped using 264 animals from a (NZB/BlNJ x NZW/LacJ)F2 intercross. A panel of 147 SNP markers spaced approximately 20 Mb apart was used for the genome scan. F2 animals were placed on an atherogenic diet at 8 weeks of age and sacrificed for phenotype analysis at 16 weeks of age. Parental strain NZW/LacJ displays higher plasma triglycerides in females, higher free fatty acid levels in males and higher glucose levels in both sexes compared to parental strain NZB/BlNJ.

On mouse Chromosome 2, two loci for blood glucose levels mapped to 72 Mb (Bglu4, blood glucose level 4) and 145 Mb (Bglu5, blood glucose level 5). The Bglu4 interval spans 60 Mb to 88 Mb and peak linkage occurs near rs3687515 with a stronger effect in males (LOD=3.6). NZB/BlNJ-derived alleles at Bglu4 confer increased blood glucose levels. G6pc2 at 69 Mb is a potential candidate gene for Bglu4. The Bglu5 interval spans 120 Mb to 175 Mb with peak linkage near rs3022911 (LOD=4.3). This locus is male-specific. NZW/LacJ-derived alleles at Bglu5 confer increased blood glucose levels in male animals. Previously identified QTL Bglu1 at 117.9 Mb overlaps with the Bglu5 interval. Ggtl3 at 155.3 Mb is a potential candidate gene for Bglu5. Linkage to free fatty acids mapped to 69 Mb near rs3726142 (LOD=1.3). This locus is named Ffaq3 (free fatty acid QTL 3) and interacts with Ffaq4 on chromosome 15. Homozygosity for NZB/BlNJ-derived alleles at Ffaq3 and Ffaq4 confers increased free fatty acid levels.

Significant linkage to free fatty acid level in males mapped to 43 Mb on mouse Chromosome 4 near rs3725792 (LOD=5.4). This locus spans 30 Mb to 60 Mb and is named Ffaq2 (free fatty acids QTL 2). NWZ/LacJ-derived alleles at Ffaq2 confer increased free fatty acids in males. Bglu6 (blood glucose level 6) mapped to 32 Mb near rs3725792 (LOD=3.5). This locus spans 21 Mb to 43 Mb and is male-specific. NZB/BlNJ-derived alleles at Bglu6 confer increased blood glucose levels in male animals. Il11ra1 (41.6 Mb) and Il11ra2 (42.7 Mb) are potential candidate genes for Bglu6. Suggestive linkage to serum triglycerides mapped to 43 Mb near rs3725792 (LOD=3.2). A potential candidate gene for the suggestive triglyceride locus is Gba2.

Significant linkage to triglyceride levels on an atherogenic diet mappedto 101 Mb on mouse Chromosome 7 near rs3670069 (LOD=3.1). This locus spans 58 Mb to 116 Mb and is named Tgq4 (triglyceride QTL 4). NZW/LacJ-derived alleles at Tgq4 confer increased triglycerides. Thrsp at 104.5 Mb is a potential candidate for Tgq4. A suggestive locus for blood glucose levels mapped to 56 Mb (LOD=2.2 at rs3708035) with a QTL interval spanning 26 Mb to 78 Mb. NZB/BlNJ-derived alleles at this locus confer increasedblood glucose levels.

On mouse Chromosome 8, significant linkage to triglyceride levels mapped to 21 Mb near rs3691954 (LOD=3.2). This locus is named Tgq5 (triglyceride QTL 5). NZW/LacJ-derived alleles at Tgq5 confer increased triglycerides. The Tgq5 interval spans 0 Mb to 50 Mb. Irs2 at 11 Mb is a potential candidate gene for Tgq5. Linkage to blood glucose levels also mapped near rs3691954 (LOD=2.3 at 24 Mb) and is named Bglu11 (blood glucose QTL 11). This locus interacts with Bglu9 on chromosome 17. Animals homozygous for NZB/BlNJ-derived alleles at Bglu11 and Bglu9 display increased blood glucose levels.

On mouse Chromosome 10, interacting loci for triglyceride levels mapped to 48 Mb (near rs3722617, LOD=1.7) and 107 Mb (near rs13480757, LOD=2.1) and are named Tgq7 (triglyceride QTL 7) and Tgq8 (triglyceride QTL 8), respectively. Homozygosity for NZB/BlNJ-derived alleles at Tgq7 in conjunction with NZW/LacJ-derived alleles at Tgq8 confers increased triglyceride levels. Significant linkage to bloodglucose levels in males mapped to 87 Mb near rs3089366 (LOD=3.9) and is named Bglu7 (blood glucose QTL 7). NZW/LacJ-derived alleles at Bglu7 confer increased blood glucose levels in males. The Bglu7 interval spans 74 Mb to 100 Mb. Previously identified QTLNfbq (114.3 Mb) maps near Bglu7. Timp3 at 85.7 Mb is a potential candidategene for Bglu7.

A locus named Ffaq4 (free fatty acid QTL 4) at 10 Mb on mouse Chromosome 15 was identified in linkage to rs3676680 (LOD=2.3). Ffaq4 interacts with Ffaq3 on chromosome 2 where homozygosity for NZB/BlNJ-derived alleles at both QTL confer increased free fatty acid levels. The 95% confidence interval for Ffaq4 spans 0 Mb to 32 Mb. Significant linkage to blood glucose levels, Bglu8, mapped to 29 Mb near rs4230721 (LOD=4.3). Bglu8 has a sex-different effect where NZB/BlNJ-derived alleles confer increased free fatty acids in males and NZW/LacJ-derived alleles confer increased free fatty acids in females. The 95% confidence interval for Bglu8 spans 15 Mb to 70 Mb. Fbgl2 (107.3 Mb) and Dbm4 (66 Mb) are previously identified QTL mapping near Bglu8. Adcy8 (64.5 Mb) is a potential candidate gene near Bglu8.

Suggestive linkage to free fatty acid levels mapped to 6 Mb on mouse Chromosome 16 near rs3090912 (LOD=3.1). The 95% confidence interval for this suggestive locus spans 0 Mb to 25 Mb. A2bp1 at 7.2 Mb and EG665158 are potential candidate genes for this locus.

Significant linkage to blood glucose levels, Bglu9, mapped to 22 Mb on mouse Chromosome 17 near rs4231344 (LOD=4.1). NZB/BlNJ-derived alleles at Bglu9 confer increased blood glucose. The 95% confidence interval spans 0 Mb to 45 Mb. Idd16 (33.7 Mb) is a previously identified diabetes QTL mapping near Bglu9.

On mouse Chromosome 18, linkage to triglyceride levels mappedto 68 Mb near rs4231907 (Tgq6, LOD=4.5) and linkage to blood glucose levels in males mapped to 33 Mb near rs3705122 (Bglu10, LOD=3.3). The 95% confidence interval for Tgq6 spans 52 Mb to 78 Mb. NZB/BlNJ-derived alleles at Tgq6 confer increased triglycerides. Ppargc1b at 61.4 Mb is a potential candidate gene for Tgq6. The Bglu10 QTL interval spans 0 Mb to 50 Mb. NZB/BlNJ-derived alleles at Bglu10 confer increased blood glucose in male animals. Ppp2r2b at 42.8 Mb is a potential candidate gene for Bglu10.

J:154142

A backcross (NZO/H1Lt x NON/LtJ) x NON/LtJ, and three intercrosses, (C57BL/6J x DBA/2J), (C57BL/6J x C3H/HeJ), and (NZB/B1NJ x NZW/LacJ) were informative in mapping QTL loci controlling plasma HDL , total cholesterol and triglyceride levels.

In the (C57BL/6J x DBA/2J) cross QTL results presented here by Phenotype, Chr, Marker, cM location , LOD, High strain

Plasma HDL , Chr 1 , Hdlq15 , 85cM , 2.8 , DBA/2J

Plasma HDL , Chr 3 , Hdlq21 , 64cM , 3.0 , C57BL/6J

Plasma HDL , Chr 4 , Hdlq64 , 3cM , 2.2 , C57BL/6J

Plasma HDL , Chr 6 , Hdlq11 , 37cM , 2.8 , DBA/2J

Plasma HDL , Chr 8 , Hdlq16 , 56cM , 4.6 , DBA/2J

Plasma HDL , Chr 12, Hdlq63 , 42cM , 2.2 , C57BL/6J

12.09.2014 Curator Note:

Because Hdlq15 was was originally mapped in J:88486 in 2004 using an (C57BL/6J x 129S1/SvImJ)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq87.

Because Hdlq21 was originally mapped inJ:89309 in 2004using an (SM/J x NZB/BlNJ)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq93.

Because Hdlq64 was originally mapped in J:142770 in 2008 using (DBA/1J x DBA/2J) crosses, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq98.

Because Hdlq11 was originally mapped in J:83460 in 2003 using a (CAST/Ei x DBA/2J)F2 cross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq85.

Because Hdlq16 was originally mapped in J:88486 in 2004 using an (C57BL/6J x 129S1/SvImJ)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq88.

Because Hdlq63 was originally mapped in J:142770 in 2008 using (DBA/1J xDBA/2J)crosses, which differs from the cross used here, we consider the current study a separate mapping experiment and have named the QTL Hdlq97.

In the (C57BL/6J x C3H/HeJ) cross

Plasma HDL , Chr 1 , Hdlq15 , 6.0cM 9.1, C3H/HeJ

Plasma HDL , Chr 11 , Hdlq74 , 42cM ,3.2, C3H/HeJ

Plasma HDL , Chr 18 , Hdlq76,37cM ,2.1, C3H/HeJ

Plasma HDL , Chr 19 , Hdlq48 , 4cM ,2.1, C57BL/6J

In the (NZO/H1Lt x NON/LtJ) x NON/LtJ cross

PlaDL , Chr1 ,Hdlq69 , 92cM , 2.4 , NON/LtJ

Plasma HDL , Chr 5 , Hdlq73, 41cM , 3.4, Heterozygous

In the (NZB/B1NJ x NZW/LacJ) cross

Plasma HDL , Chr 1 , Hdlq68 , 49cM , 3.3 , NZW/LacJ

Plasma HDL , Chr 2 , Hdlq70 , 82cM , 2.8 , NZB/B1

PlasmaHDL , Chr3 , Hdlq71 , 26cM , 4.5 , NZB/B1NJ

Plasma HDL , Chr 4 , Hdlq72 , 25cM , 3.5 , NZW/LacJ

Plasma HDL ,Chr 5 , Hdlq7 , 26cM , 9.05 , NZW/LacJ

Plasma HDL , Chr 5 , Hdlq8 , 57cM , 12.7 , NZB/B1NJ

Plasma HDL , Chr 12 , Hdlq75 , 54cM , 4.1 , NZB/B1NJ

Plasma HDL , Chr 16 , Hdlq76 , 2cM , 3.2 , NZW/LacJ

Plasma HDL , Chr 18 , Hdlq77 , 30cM,5.1 , NZW/LacJ

12.09.2014 Curator Note: Because Hdlq7 was originally mapped in J:84430 in 2003 using a (C57BL/6J x NZB/BlNJ)F1 x C57BL/6J backcross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq66.

Also, because Hdlq76 was first mapped here to Chr 18 using the C57BL/6J x C3H/HeJ cross; we have renamed the QTL mapping to 2cM on Chr16 using the (NZB/B1NJ x NZW/LacJ) cross as Hdlq101. We consider the separate crosses asseparte map experiments, mapping novel QTL.

In the (C57BL/6J x DBA/2J) cross

Triglycerides , Chr 12 , Tgq33 , 14 cM , 3.1 , C57BL/6

In the (C57BL/6J x C3H/HeJ) cross

Triglycerides , Chr 2 , Tgq32 , 80 cM , 4.7 , C3H/HeJ

Triglycerides , Chr19 ,Tgq34 , 39 cM , 3.2 , C3H/HeJ

In the (NZO/H1Lt x NON/LtJ) x NON/LtJ Cross

Triglycerides , Chr 1 , Tgq30 , 89 cM , 3.5 ,NON/LtJ

Triglycerides,Chr 2 , Tgq31,73 cM , 2.4 , NON/LtJ

In the(NZB/B1NJ x NZW/LacJ) cross

Triglycerides , Chr 7, Tgq4,50cM ,3.1 , NZW/LacJ

Triglycerides , Chr 8 , Tgq5 , 11 cM , 3.2 , NZW/LacJ

Triglycerides , Chr 18 , Tgq6 ,34 cM,1 , NZW/LacJ

In the (C57BL/6J x C3H/HeJ) cross

Total Cholesterol , Chr 1 , Tcq3, 84 , 2.2, C3H/HeJ

In the(NZO/H1Lt x NON/LtJ) x NON/LtJ cross

Total Cholesterol , Chr 8 , Tcq7 , 36 , 1.5 , Heterozygous

In the (NZB/B1NJ x NZW/Lac) cholesterol , Chr2 , Tcq4 , 83,4.0 , NZB/B1NJ

Total Cholesterol , Chr 5 , Tcq5 , 61 , 7.9 ,NZB/B1NJ

Total Cholesterol,Chr7 , Tcq6 , 62 , 2.9 , NZW/LacJ

Total Cholesterol , Chr 9 , Tcq8 , 53 , 7.7 , NZB/B1NJ

Total Cholesterol , Chr 18 , Tcq9 , 33 , 5.8, NZB/B1NJ

References

• Original: J:138463 Su Z, et al., Candidate genes for plasma triglyceride, FFA, and glucose revealed from an intercross between inbred mouse strains NZB/B1NJ and NZW/LacJ. J Lipid Res. 2008 Jul;49(7):1500-10
• All: 1 reference(s)