Asdq1^129T2/SvEms
QTL Variant Detail

Summary

• QTL variant: Asdq1^129T2/SvEms
• Name: atrial septal defect QTL 1; 129T2/SvEms
• MGI ID: MGI:3619572
• QTL: Asdq1 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: 129T2/SvEms

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased foramen ovale width compared to QSi5. (J:106106)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:106106

Linkage analysis was performed on 1437 (QSi5 x 129T2/SvEms)F2 intercross animals to map QTL associated with cardiac atrial septal defect (ASD) morphologies. 89 markers at an average spacing of 17 cM were used in the genome scan. LOD scores greater than 4.3 were considered significant, and greater than 2.8 were considered suggestive. Parental strain 129T2/SvEms exhibits shorter flap valve length (FVL) and significantly higher incidence of patent foramen ovale (PFO) compared to parental strain QSi5. Foramen ovale width (FOW) does not differ significantly between 129T2/SvEms and QSi5.

Significant linkage to foramen ovale width mapped to mouse Chromosome 1. This locus is named Asdq1 (atrial septal defect QTL 1). Peak linkage occurs at 68 Mb (34 cM) with LOD=5.89 and the QTL interval spans 43 Mb - 102 Mb. 129T2/SvEms-derived alleles at Asdq1 confer increased foramen oval width. This locus explains 3.6% of the variance.

Significant linkage to foramen oval width mapped to mouse Chromosome 2. This locus is named Asdq2 (atrial septal defect QTL 2). Peak linkage occurs at 137 Mb (63 cM) with LOD=4.39. The QTL interval of Asdq2 spans 115 Mb - 154 Mb. This locus explains 3.1% of the variance and 129T2/SvEms-derived alleles at Asdq2 confer decreased foramen ovale width. Cardiac actin gene Actc1 at 64 cM is a potential candidate for Asdq2 as it maps to the QTL interval and the human ortholog ACTC has been implicated in autosomal dominant atrial septal defects.

Significant linkage to foramen ovale width mapped to 49 Mb (24 cM) on mouse Chromosome 4 with LOD=9.05. This locus is named Asdq3 (atrial septal defect QTL 3) and explains 5.6% of the variance. The QTL interval spans 26 Mb - 80 Mb and 129T2/SvEms-derived alleles at this locus confer decreased foramen ovale width.

Linkage to flap valve length mapped to 142 Mb (59 cM) on mouse Chromosome 6 with LOD=4.11. The LOD score is just below the significance threshold and authors state binary analysis suggests strong evidence for a QTL at this locus, named Asdq4 (atrial septal defect QTL 4.) The QTL interval of Asdq4 spans 118 cM - telomere. 129T2/SvEms-derived alleles at Asdq4 confer decreased flap valve length. This locus explains 2.4% of the variance.

Significant linkage to flap valve length mapped to 13 Mb (9 cM) on mouse Chromosome 19 with LOD=6.04. This locus is named Asdq5 (atrial septal defect QTL 5) and also shows suggestive linkage to patent foramen ovale. The QTL interval of Asdq5 spans 0 Mb - 46 Mb. 129St/SvEms-derived alleles at Asdq5 confers decreased flap valve length. This locus explains 3.5% of the variance.

Significant linkage to flap valve length mapped to 114 Mb (60 cM) on mouse Chromosome 8 with LOD=5.52. This locus is named Asdq6 (atrial septal defect QTL 6) and spans 108 Mb - telomere. Asdq6explains 3.4% of the variance with 129T2/SvEms-derived alleles conferring decreased flap valve length.

Significant linkage to flap valve length mapped to 37 Mb (10 cM) on mouse Chromosome 13 with LOD=4.64. This locus is named Asdq7 (atrial septal defect QTL 7) and the QTL interval spans 6.5 Mb - 48 Mb. Asdq7 explains 2.6% of the variance with 129T2/SvEms-derived alleles conferring decreased flap valve length.

Suggestive linkage to flap valve length mapped to 118 Mb (68 cM) on mouse Chromosome 10 withLOD=3.8, 53 Mb (24 cM) on mouse Chromosome 15 with LOD=3.56, and 40 Mb (11 cM) on mouse Chromosome 16 with LOD=3.05. Suggestive linkage to foramen ovale width mapped to 37 Mb (13 cM) on mouse Chromosome 9 with LOD=3.43.

References

• Original: J:106106 Kirk EP, et al., Quantitative trait loci modifying cardiac atrial septal morphology and risk of patent foramen ovale in the mouse. Circ Res. 2006 Mar 17;98(5):651-8
• All: 1 reference(s)