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Maternal Genetic Risk Factors for Infant Zinc Deficiency
Author(s) -
Friel James,
Juan Sandra Castilo San,
Qasem Wafaa,
Leon Alejandra Serrano,
Yurkova Natasha,
Eck Peter
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.628.2
Subject(s) - secretion , biology , plasmid , single nucleotide polymorphism , zinc deficiency (plant disorder) , zinc , genotype , genetics , gene , biochemistry , chemistry , organic chemistry
Zinc is an essential constituent of catalytic sites of multiple enzymes. Since all of these enzymes are involved in cellular functions, zinc deficiency will have adverse effects on reproduction, normal growth and development. Zinc deficiency was reported in healthy term infants and attributed to a decrease in zinc secretion in maternal breast milk (BM). Two single nucleotide polymorphisms (SNPs) in the membrane transporter SLC30A2 (ZnT2) cause decreased zinc secretion into BM. Through bioinformatics analysis we identified 14 additional SNPs causing amino acid changes. We aim to identify the functional changes caused by these 14 SNPs, with the initial objective to identify possible cellular mislocalization. We subcloned the SLC30A2 open reading frames into the Gateway entry plasmid pDONR221 and introduced the 14 SNPs using site directed mutagenesis. During transfer into expression plasmid we tagged SLC30A2 with red and green fluorescent proteins (mCherry, tGFP). We transfected individual plasmids into mammary epithelial cells and observed cellular targeting using epifluorescent imaging. The most common variants locate to secreting endosomes in mammary epithelial cells. Incorrect targeting of SLC30A2 eliminates its role in zinc secretion, resulting in zinc depleted BM. Mothers carrying risk genotypes for infant zinc deficiency can be identified. Funded by CRC and CIHR