Moaq1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Moaq1^C57BL/6J
• Name: modifier of alien QTL 1; C57BL/6J
• MGI ID: MGI:6402804
• QTL: Moaq1 Location: Chr4:19500000-46000000 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:282171

The primary cilium is a signaling center critical for proper embryonic development. Previous studies have demonstrated that mice lacking Ttc21b (homozygous for the

alien (aln) null allele of Ttc21b) have impaired retrograde trafficking within the cilium and multiple organogenesis phenotypes, including microcephaly. The severity of the microcephaly in Ttc21b^aln/aln homozygous null mutants is considerably affected by the genetic background; mutants on an FVB/NJ (FVB) background develop a forebrain significantly smaller than mutants on a C57BL/6J (B6) background.

The authors performed a QTL analysis on FVB.A-Ttc21b^aln and B6.A(FVB)-Ttc21b^aln mice to identify potential genetic modifiers. GigaMUGA and MegaMUGA genotyping of recombinants was performed by GeneSeek (Neogen; Lincoln, NE). Linkage mapping, including scanone and scantwo analyses, was performed on informative SNP markers and brain sizes (mm^2) of 96 F2 recombinants using the R/qtl software package. All genome coordinates relative to NCBIm37 (mm9).

QTL analysis identified two regions linked to differential forebrain size:

Moaq1 (modifier of alien QTL 1) maps to Chr 4: 19.5 - 46 Mb with a peak LOD score of 6.1 at 27.8 Mb (UNC6953268). Moaq1 explains 25.1% of the phenotypic variance and is significant at the genomewide level (p < 0.05).

Moaq2 (modifier of alien QTL 2) maps to Chr 6: 0 - 117.5 Mb with a peak LOD score of 4.7 at 93.6 Mb (UNCHS018175). Moaq2 explainx 20.1% of the phenotypic variance and is suggestive at the genomewide level (p < 0.63).

These QTL were validated by constructing congenic strains.

Further analysis of Moaq1 identified Gpr63 as a candidate gene.

References

• Original: J:282171 Snedeker J, et al., Gpr63 is a modifier of microcephaly in Ttc21b mouse mutants. PLoS Genet. 2019 Nov;15(11):e1008467
• All: 1 reference(s)