Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  3
• Reference
  J:265987 Hadsell DL, et al., In silico mapping of quantitative trait loci (QTL) regulating the milk ionome in mice identifies a milk iron locus on chromosome 1. Mamm Genome. 2018 Oct;29(9-10):632-655
• ID
  MGI:6488403

Genes

Gene	Assay Type
Mmcq1	visible phenotype
Mmcq16	visible phenotype
Mmcq17	visible phenotype

Notes

• Experiment
  The breast-feeding neonate depends on mothers milk for both macronutrients and micronutrients including minerals. The goals of the present study were to document the effects of genetic background in mice on milk concentrations of select minerals and to use genome-wide association study (GWAS) to identify QTL regulating milk mineral concentrations.
  
  Milk samples from lactating mice in each of 31 different inbred strains of the mouse diversity panel (MDP) were analyzed by inductively coupled plasmaoptical emission spectroscopy to determine the concentrations of calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), sodium (Na), phosphorus (P), sulfur (S), and zinc (Zn).
  
  GWAS was conducted using the efficient mixed model analysis (EMMA) package in R (Kang et al. 2008) in conjunction with a composite SNP dataset that was obtained from the Mouse Phenome Database (http://phenome.jax.org/). A dataset of 437,730 SNPs referred to as the 400k set, was prepared as previously described (Hadsell et al. 2015).
  
  A total of 17 QTL were detected across the nine minerals analyzed with effect sizes accounting for 1030% of total variation (all genome coordinates relative to GRCm38/mm10). GWAS identified a single pleiotropic milk mineral concentration QTL (Mmcq) on chromosome 3 for Ca, Mg, and P, which we have separated into three separate QTL based on mineral phenotype:
  
  Mmcq1 (milk mineral concentration QTL 1, Ca) maps to Chr 3: 69,213,377 - 70,533,031 bp with a peak p-value of 2.99E11 at 69,348,008 bp (rs30999878).
  
  Mmcq16 (milk mineral concentration QTL 16, Mg) maps to Chr 3: 69,213,377 - 70,533,031 bp with a peak p-value of 2.99E11 at 69,348,008 bp (rs30999878).
  
  Mmcq17 (milk mineral concentration QTL 17, P) maps to Chr 3: 69,213,377 - 70,533,031 bp with a peak p-value of 2.99E11 at 69,348,008 bp (rs30999878).
  
  Mmcq2 (milk mineral concentration QTL 2, Zn) maps to Chr 11: 115,663,711 - 116,738,538 bp with a peak p-value of 3.45E10 at 116,052,712 bp (rs27046382).
  
  Mmcq3 (milk mineral concentration QTL 3, K) maps to Chr 1: 182,005,966 - 182,401,482 bp with a peak p-value of 5.14E08 at 182,275,811 bp (rs32599364).
  
  Mmcq4 (milk mineral concentration QTL 4, Zn) maps to Chr 12: 13,841,779 - 15,656,288 bp with a peak p-value of 5.31E08 at 15,604,418 bp (rs46732757).
  
  Mmcq5 (milk mineral concentration QTL 5, Fe) maps to Chr 14: 149,549,620 - 151,007,689 bp with a peak p-value of 5.63E08 at 150,215,001 bp (rs32365572).
  
  Mmcq6 (milk mineral concentration QTL 6, Fe) maps to Chr 17: 87,578,269 - 90,935,570 bp with a peak p-value of 8.15E08 at 90,935,570 bp (rs33492954).
  
  Mmcq7 (milk mineral concentration QTL 7, K) maps to Chr 11: 3,335,983 - 5,998,502 bp with a peak p-value of 3.02E07 at 3,335,983 bp (rs26884173).
  
  Mmcq8 (milk mineral concentration QTL 8, Zn) maps to Chr 6: 125,899,344 - 126,375,383 bp with a peak p-value of 4.33E07 at 126,537,268 bp (rs36383182).
  
  Mmcq9 (milk mineral concentration QTL 9, Fe) maps to Chr 1: 26,301,591 - 51,676,397 bp with a peak p-value of 7.05E07 at 38,523,729 bp (rs30863680).
  
  Mmcq10 (milk mineral concentration QTL 10, Fe) maps to Chr 12: 88,902,986 - 92,129,941 bp with a peak p-value of 7.05E07 at 92,076,476 bp (rs46203900).
  
  Mmcq11 (milk mineral concentration QTL 11, Fe) maps to Chr 13: 66,605,527 - 74,327,227 bp with a peak p-value of 7.05E07 at 69,978,707 bp (rs29509708).
  
  Mmcq12 (milk mineral concentration QTL 12, Fe) maps to Chr 12: 65,102,180 - 74,720,737 bp with a peak p-value of 7.88E07 at 67,865,094 bp (rs32221670).
  
  Mmcq13 (milk mineral concentration QTL 13, K) maps to Chr 19: 22,070,531 - 25,931,265 bp with a peak p-value of 8.14E07 at 24,151,170 bp (rs50359915).
  
  Mmcq14 (milk mineral concentration QTL 14, K) maps to Chr 1: 169,904,372 - 170,653,082 bp with a peak p-value of 1.05E06 at 169,904,463 bp (rs31486545).
  
  Mmcq15 (milk mineral concentration QTL 15, S) maps to Chr 2: 69,308,444 - 70,560,125 bp with a peak p-value of 2.30E06 at 69,308,444 bp (rs8263229).
  
  Intersecting the Mmcq with published chromatin immunoprecipitation sequence data identified 15 out of 4633 high-linkage disequilibrium singlenucleotide polymorphisms that resided in signal transducer and activation of transcription 5 (STAT5) binding regions. A milk Fe-associated locus (Mmcq9) on chromosome 1 contained an SNP that localized to a STAT5 binding region and intersected with a HOMER motif predicted to bind the transcriptional regulator E74-Like ETS transcription factor 5. This locus also contained the genes for solute carrier family (Slc) members Slc9a2, Slc9a4, Slc39a10, and Slc40a1. Expression analysis of these transporters supports the conclusion that Slc9a2 and Slc40a1 within the mammary gland could mediate the effect of Mmcq9 on milk Fe concentration.