Whole mitogenome sequencing uncovers a relation between mitochondrial heteroplasmy and leprosy severity

• Published in: Human genomics Vol. 17; no. 1; pp. 110 - 15
• Main Authors: de Souza, Felipe Gouvea, da Silva, Moisés Batista, de Araújo, Gilderlanio S, Silva, Caio S, Pinheiro, Andrey Henrique Gama, Cáceres-Durán, Miguel Ángel, Santana-da-Silva, Mayara Natália, Pinto, Pablo, Gobbo, Angélica Rita, da Costa, Patrícia Fagundes, Salgado, Claudio Guedes, Ribeiro-Dos-Santos, Ândrea, Cavalcante, Giovanna C
• Format: Journal Article
• Language: English
• Published: England BioMed Central 08-12-2023; BMC
• Subjects: Bacterial infections; Bioinformatics; Carbon dioxide; Disease; Genome, Mitochondrial - genetics; Genomes; Haplogroups; Health care; Heteroplasmy; Humans; Immune system; Infections; Laboratories; Leprosy; Leprosy - genetics; Metabolism; Mitochondria; Mitochondria - genetics; Mitochondrial DNA; Mitogenome; mtDNA; Mutation; Mycobacterium leprae; Nervous system; Brazil; United States > US; Leprosy; Haplogroups; Mycobacterium leprae; Mitogenome; mtDNA
• ISSN: 1479-7364; 1473-9542; 1479-7364
• DOI: 10.1186/s40246-023-00555-8

In recent years, the mitochondria/immune system interaction has been proposed, so that variants of mitochondrial genome and levels of heteroplasmy might deregulate important metabolic processes in fighting infections, such as leprosy.
We sequenced the whole mitochondrial genome to investigate variants and heteroplasmy levels, considering patients with different clinical forms of leprosy and household contacts. After sequencing, a specific pipeline was used for preparation and bioinformatics analysis to select heteroplasmic variants.
We found 116 variants in at least two of the subtypes of the case group (Borderline Tuberculoid, Borderline Lepromatous, Lepromatous), suggesting a possible clinical significance to these variants. Notably, 15 variants were exclusively found in these three clinical forms, of which five variants stand out for being missense (m.3791T > C in MT-ND1, m.5317C > A in MT-ND2, m.8545G > A in MT-ATP8, m.9044T > C in MT-ATP6 and m.15837T > C in MT-CYB). In addition, we found 26 variants shared only by leprosy poles, of which two are characterized as missense (m.4248T > C in MT-ND1 and m.8027G > A in MT-CO2).
We found a significant number of variants and heteroplasmy levels in the leprosy patients from our cohort, as well as six genes that may influence leprosy susceptibility, suggesting for the first time that the mitogenome might be involved with the leprosy process, distinction of clinical forms and severity. Thus, future studies are needed to help understand the genetic consequences of these variants.