Variations Analysis of Mitochondrial Cytochrome b (MT-CYB) Gene in Malnourished Children from Senegal

Abstract

Introduction: Child malnutrition is a major cause of infant morbidity and mortality
worldwide and thus a major public health problem. The study of interactions between
nutrition and genes— nutritional genomics—encompasses two domains: nutrigenetics and
nutrigenomics. Malnutrition (deficiency or excess) can thus affect gene expression and
genome stability. Objective: The objective of this work is to investigate mutations of interest
of Mitochondrial Cytochrome b (MT-CYB) that may be related to child malnutrition and to
study the genetic diversity of MT-CYB. Materials and methods: We analyzed the variability
of MT-CYB in 23 malnourished children and six healthy children via PCR-sequencing. The
search of mutations in the MT-CYB gene was conducted using Surveyor Mutation software.
Nine prediction software programs (i.e., SIFT, PROVEAN, POLYPHEN-2, DEOGEN,
SNPs & go, PREDICTSNP, MUTATIONTASTER, PANTHER, and FATHMM) were used
to determine the functional impact of mutations. The various parameters of the genetic
variety as well as the genetic differentiation of MT-CYB were obtained using DNAsp Version
5.1001, Harlequin Version 3.1 and Mega X. Results: A total of 24 mutations (Z-score ≥ 20)
were identified in malnourished and healthy children. Among the non-synonym mutations
present in malnourished children, mutations p.N206N/I, p.T336H, p.Y345A, p.T348T/N,
and p.L357L/V were predicted pathogenic by at least five predictive software programs.
The amino acids Ile, Lys, Arg and Asn demonstrate significant differences between normal
and malnourished children. There is a predominance of T+A (53.72%) compared to C+G
(46.28%). Our results show high haplotypic diversity (1.000+/-0.013) and low nucleotide
diversity (0.10545+/- 0.00488). Conclusion: Our results allowed us to detect mutations in the
MT-CYB gene that could be linked to childhood malnutrition. A decrease in isoleucine (Ile),
asparagine (Asn), and arginine (Arg) may be correlated with the risk of malnutrition. This
study will allow to readjust the strategies to fight against malnutrition.