Dfs1^A/J
QTL Variant Detail

Summary

• QTL variant: Dfs1^A/J
• Name: dental fluorosis suseptibility 1; A/J
• MGI ID: MGI:5691968
• QTL: Dfs1 Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:153399

A/J mice are susceptible to dental fluorosis whereas 129/F3 mice are resistant. A total of 458 (A/J X 129P3)F2 mice were analyzed in a genome wide scan(354 SNPs) to map QTL that effect susceptibility to fluorosis in mice. A significant association was found in mouse Chromosome 2 and 11. The chromosome 2 QTL , Dfs1, segregated with flanking markers rs13476589 and UT_2_156.443943. The QTL interval in chromosome 11 for Dfs2 was defined by flanking markers rs3708339 and rs6161623. A suggested genome location for Dfs1 was 77.62 Mb and 74.29 for Dfs2.

J:237166

Genetic factors underlie dental fluorosis (DF) susceptibility/resistance. The A/J (DF susceptible) and 129P3/J (DF resistant) inbred strains have been previously used to detect quantitative trait loci (QTL), Dfs1 and Dfs2 respectively, associated with DF on chromosomes Chr 2 and 11 [J:153399].

In the present study increased marker density genotyping followed by interval mapping was performed to narrow the QTL intervals and improve the LOD scores. From an initial panel of 458 F2 mice (11) genomic DNAs from 140 mice representing DF phenotype extremes were selected for additional SNP genotyping. Among these 140 mice 75 were from the low DF group and 65 were from the high DF group. 112 SNPs representing Chrs 2 and 11 were selected and genotyped utilizing the Genetic Analysis service at The Jackson Laboratory (Bar Harbor, ME USA).

The SNP assays selected detected polymorphisms between A/J and 129P3/J and increased the number of informative SNPs from 29 to 108 for Chr 2 and from 14 to 47 for Chr 11. Interval mapping was performed in R with R/qtl package. SNP datasets of the A/J and 129P3/J inbred strains from the Imputed Diversity Array, Build37 were used with the Mouse Strain Comparison Tool (The Center for Genome Dynamics at the The Jackson Laboratory, Bar Harbor, ME USA).

Interval mapping using increased marker densities on Chrs 2 and 11 resulted in a modest narrowing of the respective QTL intervals and an improved estimation of maximum LOD scores with peak LOD = 8.252 located at marker rs4223510 (68 cM in an interval mapping between 65-74 cM) on Chr 2 for QTL Dfs1 and a peak LOD = 8.845 located at marker rs3694522 (35 cM in an interval mapping between 31-45 cM) on Chr 11 for QTL Dfs2.

Accn1 residing at 80,693,67181,781,959 bp on Chr 11 was selected for further investigation. Following F treatment Accn1null mice developed DF that was not statistically different from the DF in similarly treatedC57BL/6J mice (Fig. 4)(Table 3). The data suggest that loss of function of Accn1 alone in the C57BL/6J strain is either insufficient (not a major effect gene) to contribute to DFsusceptibility, that Accn1 plays no direct role in DF susceptibility, or there is epistasis between other C57BL/6J alleles.

References

• Original: J:153399 Everett ET, et al., Detection of dental fluorosis-associated quantitative trait Loci on mouse chromosomes 2 and 11. Cells Tissues Organs. 2009;189(1-4):212-8
• All: 2 reference(s)