In silico mapping of quantitative trait loci (QTL) regulating the milk ionome in mice identifies a milk iron locus on chromosome 1

Abstract

The breast-feeding neonate depends on mother's 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 quantitative trait loci (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 plasma-optical 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 identified a single pleiotropic milk mineral concentration QTL (Mmcq) on chromosome 3 for Ca, Mg, and P. For the remaining minerals, six QTL were detected for Fe, four for K, three for Zn, and one for S. Intersecting the Mmcq with published chromatin immunoprecipitation sequence data identified 15 out of 4633 high-linkage disequilibrium single-nucleotide 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.

Review: Research Progress of Dairy Sheep Milk Genes

“…The solute carrier family is made up of different transporter families that include ion channels and exchangers, its passive transporters SLC2A2 is located on chromosomes 1 and belongs to the passive transporters, which are related to the biological process of carbohydrate metabolic process and insulin secretion regulation [42]. Many researchers have found this gene is related to milk synthesis and milk lactation [43][44][45]. In H. Marina's research [46], GWAS and post -GWAS were done in two dairy sheep breeds of 2020 ewes, and different analysis was performed to detect candidate genes associated with milk production and composition traits, as well as cheese making traits.…”

1,135 ionomes reveal the global pattern of leaf and seed mineral nutrient and trace element diversity in Arabidopsis thaliana

“…The coupling of the analyses of the ionome with genome-enabled genetics is termed ionomics (Salt, Baxter and Lahner, 2008). Ionomics has been successfully applied in plants and other organisms such as yeast (Eide et al, 2005;Yu et al, 2011Yu et al, , 2012, milk (Hadsell et al, 2018), human serum (Konz et al, 2017), mammalian organs (Ma et al, 2015) and human cell lines (Malinouski et al, 2014). Plants, being sessile organisms, have evolved intricate regulatory mechanisms to balance uptake and distribution of mineral nutrients and trace elements in response to physical and chemical variation of the soil.…”

Full species-wide leaf and seed ionomic diversity ofArabidopsis thaliana

“…The coupling of the analyses of the ionome with genome-enabled genetics is termed ionomics (Salt, Baxter and Lahner, 2008). Ionomics have been successfully applied in other organisms such as yeast (Eide et al ., 2005; Yu et al ., 2011, 2012), milk (Hadsell et al ., 2018), human serum (Konz et al ., 2017), mammalian organs (Ma et al ., 2015) and human cell lines (Malinouski et al ., 2014). Plants being sessile organisms, have evolved intricate regulatory mechanisms to balance uptake and distribution of mineral nutrients and trace elements in response to physical and chemical variation of the soil.…”