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Vmbic9C57BL/6J
QTL Variant Detail
Summary
QTL variant: Vmbic9C57BL/6J
Name: ventral midbrain iron content 9; C57BL/6J
MGI ID: MGI:3036630
QTL: Vmbic9  Location: unknown  Genetic Position: Chr17, cM position of peak correlated region/allele: 22.26 cM
QTL Note: genome coordinates based on the marker associated with the peak LOD score
Variant
origin
Strain of Specimen:  C57BL/6J
Variant
description
Allele Type:    QTL
Notes

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

J:87918

15 BXD/Ty recombinant inbred (RI) strains were used to map QTLs associated with regional brain and liver iron content. (The BXD/Ty RI strains are derived from C57BL/6J and DBA/2J parental inbred strains.) Authors used P=0.01 as the cutoff point for statistical significance.

The following QTLs associated with ventral midbrain iron content (Vmbic) were identified:

Vmbic1 mapped to 81.6 cM on mouse Chromosome 1 near D1Mit425.

Vmbic2 mapped to 26 cM on mouse Chromosome 5 near D5Mit79.

Vmbic3 mapped to 65.2 cM on mouse Chromosome 7 near D7Mit371. Inheritance of C57BL/6J-derived alleles at Vmbic3 confers a 2-fold increase in VMB iron content compared to DBA/2J-derived alleles. This locus explains 56% of the phenotypic variance. Th (tyrosine hydroxylase) maps near Vmbic3 and may be a possible candidate gene.

Vmbic4 mapped to 15 cM on mouse Chromosome 7 near D7Mit246.

Vmbic5 mapped between 31 cM (D9Mit21) - 35 cM (D9Mit104) on mouse Chromosome 9. A potential candidate gene mapping near Vmbic5 is Drd2 (dopamine receptor 2).

Vmbic6 mapped to 44.8 cM on mouse Chromosome 11 near D11Mit245.

Vmbic7 mapped to 68 cM on mouse Chromosome 13 near D13Mit196. Vmbic7 is specific to female animals.

Vmbic8 mapped to 19 cM on mouse Chromosome 14 near D14Mit214. Inheritance of C57BL/6J-derived alleles at Vmbic3 confer a 25% increase in VMB iron content in male animals compared to DBA/2J-derived alleles.

Vmbic9 mapped to 22.8 cM on mouse Chromosome 17 near D17Mit11.

Vmbic10 mapped between 20 cM (D11Mit296) - 28 cM (D11Mit86) on mouse Chromosome 11. Candidate genes mapping near Vmbic10 include Gabra1, Gabrg2, and Adra1b.

The following QTLs associated with liver iron content (Lvic) were identified:

Lvic1 mapped between 78.7 cM (D2Mit412) and 95.5 cM (D2Mit51) on mouse Chromosome 2. Lvic1 is specific to female animals. A potential candidate gene mapping near Lvic1 is Ftl1-rs2 (ferritin light chain related sequence 2).

Lvic2 mapped to 49.2 cM on mouse Chromosome 3 near D3Mit12.

Lvic3 mapped between 64 cM (D6Mit301) - 74cM (D6Mit374) on mouse Chromosome 6. Lvic3 is specific to male animals.

Lvic4 mapped to 54 cM on mouse Chromosome 14 near D14Mit185. Lvic4 is specific to female animals.

Lvic5 mapped between 17.25 cM (DXMit68) - 20 cM (DXMit144) on mouse Chromosome X.

J:114154

Linkage analysis was performed on 15 BXD/Ty recombinant inbred (RI) strains to identify QTLs associated with copper and zinc regulation in the brain. BXD/Ty RI strains are derived from C57BL/6J and DBA/2J inbred strains. Animals were tested at an averageage of 120 days. Loci reaching LOD>2.8 are reported, and were compared to brain iron content QTL from a previous experiment by Jones et al (2003).

On mouse Chromosome 1, highly significant linkage to zinc in the prefrontal cortex in females mapped to 155.64 Mb (81 cM) with LOD=5.41. This locus is named Bczr1 (brain copper/zinc regulation 1). Bczr1 also shows suggestive linkage to zinc in the ventral midbrain in females (LOD=2.37). Potential candidate genes mapping near this region include Cacna1e (86 cM) and Kcnj10 (93.5 cM). Bczr1 colocalizes with previously identified QTL Vmbic1 at 81.6 cM and may represent the same locus.

On mouse Chromosome 8, significant linkage to zinc in the nucleus accumbens in females mapped to 55.72 Mb (31 cM) with LOD=3.59.This locus is named Bczr2 (brain copper/zinc regulation 2). Hpgd is a potential candidate genes mapping near Bczr2.

On mouse Chromosome 16, significant linkage to copper in the caudate-putamen in males mapped to 61.1 MB (40 cM) with LOD=3.69. This locusisnamed Bczr3 (brain copper/zinc regulation 3). Potential candidate genes mapping near Bczr3 include Epha6, Pros1, and Epha3.

On mouse Chromosome 17, linkage to copper and zinc in the prefrontal cortex in males mapped to 42.82 Mb near D17Mit49 (23.2 cM) with LOD= 3.79 and LOD=3.33, respectively. This locus is the same as Vmbic9 (ventral midbrain iron content 9), a QTL identified in the same set of BXD/Ty RI strains in a previous experiment. Males carrying DBA/2J-derived alleles at Vmbic9 exhibit on average 16% increased zinc concentration in the prefrontal cortex, 72% increased copper concentration in the prefrontal cortex, and 34% increased iron concentration in the caudate-putamen. Vmbic9 also shows linkage to zinc in the nucleus accumbens in males andfemales with LOD=2.28 and LOD=3.52, respectively. Males and females carrying DBA/2J-derived alleles at Vmbic9 exhibit on average 32% increased zinc concentration in the nucleus accumbens and 45% increased iron concentration in the ventral midbrain. The H2 locus (23 cM) maps near Vmbic9. Previously identified loci for seizure threshold susceptibility (McCall 1981; Plomin 1991) also map near Vmbic9.

Suggestive linkage to copper in the caudate-putamen and nucleus accumbens in females mapped to approximately 27 Mb on mouse Chromosome 12 (LOD=2.84 and LOD=2.35, respectively). Suggestive linkage to copper and zinc in the prefrontal cortex in males mapped to 20.71 Mb on mouse Chromosome 3 (LOD=3.15), 109.66 Mb on mouse Chromosome 13 (LOD=2.82), and 27.2 Mb on mouse Chromosome 17 (LOD=4.03).

References
Original:  J:87918 Jones BC, et al., Quantitative genetic analysis of ventral midbrain and liver iron in BXD recombinant inbred mice. Nutr Neurosci. 2003 Dec;6(6):369-77
All:  2 reference(s)

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last database update
04/16/2024
MGI 6.23
The Jackson Laboratory