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

Autor: de Souza FG; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., da Silva MB; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Marituba, PA, 67105-290, Brazil., de Araújo GS; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., Silva CS; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., Pinheiro AHG; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., Cáceres-Durán MÁ; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., Santana-da-Silva MN; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., Pinto P; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil., Gobbo AR; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Marituba, PA, 67105-290, Brazil., da Costa PF; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Marituba, PA, 67105-290, Brazil., Salgado CG; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Marituba, PA, 67105-290, Brazil., Ribeiro-Dos-Santos Â; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil. akelyufpa@gmail.com., Cavalcante GC; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil. giovannaccavalcante@gmail.com.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2023 Dec 08; Vol. 17 (1), pp. 110. Date of Electronic Publication: 2023 Dec 08.
DOI: 10.1186/s40246-023-00555-8
Abstrakt: Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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