Related Experiment Videos
Aberrant one-carbon metabolism and ancestral genetics underlie edematous severe acute malnutrition
Natasha C Lie1,2, Yixing Han2, Qing Li2
1Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, USA.
Abstract:
Edematous severe childhood malnutrition is distinct from the non-edematous form of malnutrition and remains a major cause of under-five mortality. Its etiology remains unclear, although aberrant one-carbon metabolism has emerged as a potential contributor. Here, we assess genetic variants at loci known to influence one-carbon metabolism, and determine their association with edematous malnutrition in Jamaica and Malawi. Six loci show evidence of association, including four related to homocysteine and folate metabolism - AHCYL1, PRICKLE2, GABBR2, and PLD2, with SNPs at the latter three also having direct effects on homocysteine-related metabolites in Mendelian Randomization. Collectively, one-carbon metabolism-related variants were significantly associated with edematous malnutrition (z = 3.2), with population differences linked to a shared East African genetic ancestry and distinct signatures of selection. These findings strengthen evidence implicating aberrant one-carbon metabolism in edematous malnutrition and highlight the utility of cell-free DNA, intra-continental admixture, and population genetics for mapping disease risk.
Related Concept Videos
Overview of Protein Metabolism
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
Inborn Errors of Metabolism
Anorexia Nervosa
Symptoms and Physical Effects
Individuals with anorexia nervosa commonly exhibit extreme...
Metabolic States of the Body: Fasting and Starvation
Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Overview of Carbohydrate Metabolism
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...