Sox10m5^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Sox10m5^C57BL/6J
• Name: Sox10Dom modifier 5; C57BL/6J
• MGI ID: MGI:3699514
• QTL: Sox10m5 Location: unknown Genetic Position: Chr11, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased aganglionosis penetrance/severity and increased affected gut length compared to C3H/HeJ. (J:118320)
• Inheritance: Other (see notes)

Notes

Agln4 exhibits additive inheritance.

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

J:118320

Whole genome scan of the 19 autosomes and X chromosome was performed on (C57BL/6J-Sox10^Dom x C3H/HeJ)F2 intercross animals using single nucleotide polymorphisms (SNPs) spaced ~18 cM apart. The Sox10^Dom mutation results in neural crest defects similarto those found in Hirschsprung disease in humans. F2 animals homozygous for Sox10^Dom were scored for aganglionosis severity and penetrance as well as total affected gut length.

A modifier of Sox10^Dom mapped to 15 cM - 23 cM on mouse Chromosome 5 and is designated Agln1(Sox10m3) (aganglionosis modifier 1). Peak linkage to aganglionosis severity (LOD=7) and penetrance (LOD=8.6) occurs at 21 cM near D5Ncnp1. Agln1 is also linked to total affected gut length (LOD=16.7). C57BL/6J-derived alleles at Agln1 confer increased aganglionosis with an additive mode of inheritance. Potential candidate genes located in the 1.5-LOD support interval include Uchl1 (36 cM), Atp8a1, and Phox2b (40 cM). These genes are known to be expressed in enteric neural crest cells in the embryonic gut.

Agln2(Sox10m2) (aganglionosis modifier 2) mapped to 80 cM on mouse Chromosome 3. Agln2 is linked to aganglionosis (LOD=4.1) and affected gut length (LOD=5.4), and the 1.5-LOD support interval spans 58 cM - 89 cM. C57BL/6J-derived alleles at Agln2 confer decreased aganglionosis severity and penetrance with an additive mode of inheritance.

Agln3 (Sox10m4)(aganglionosis modifier 3) mapped to 4 cM on mouse Chromosome 8 with LOD=6.3 for aganglionosis and LOD=7.1 for total affected gut length. C57BL/6J-derived alleles at Agln3 confer increased aganglionosis and affected gut length with additive inheritance. The 1.5-LOD support interval for Agln3 spans 0 cM - 20 cM.

Agln4 (Sox10m5)(aganglionosis modifier 4) mapped to 42 cM on mouse Chromosome 11 with LOD=6.9 for aganglionosis and LOD=6.9 for total affected gut length. The 1.5-LOD support interval spans 28 cM - 69 cM. C57BL/6J-derived alleles at Agln4 confer increased aganglionosis and affected gut length with additive inheritance.

Ednrb (Sox10m1) at 54 cM on mouse Chromosome 14 showed significant linkage to aganglionosis (LOD=13.8) and total affected gut length (LOD=13.7). This locus has previously been identified as a modifier of Sox10^Dom.

References

• Original: J:118320 Owens SE, et al., Genome-wide linkage identifies novel modifier loci of aganglionosis in the Sox10Dom model of Hirschsprung disease. Hum Mol Genet. 2005 Jun 1;14(11):1549-58
• All: 1 reference(s)