02661nas a2200349   4500000000100000008004100001260001200042653001600054653001200070653001500082653001500097653001000112100001500122700001500137700001700152700001200169700001500181700002200196700002300218700001200241700001200253700001500265700001400280700002500294700001700319245010900336856008500445300000900530490000700539520175100546022001402297       2023                            d  c12/202310aHaplogroups10aleprosy10aMitogenome10atratamento10amtDNA1 ade Souza F1 ada Silva M1 ade Araújo G1 aSilva C1 aPinheiro A1 aCáceres-Durán M1 aSantana-da-Silva M1 aPinto P1 aGobbo A1 ada Costa P1 aSalgado C1 aRibeiro-Dos-Santos A1 aCavalcante G00aWhole mitogenome sequencing uncovers a relation between mitochondrial heteroplasmy and leprosy severity.  uhttps://humgenomics.biomedcentral.com/counter/pdf/10.1186/s40246-023-00555-8.pdf  a1-150 v173 a<p><strong>Background: </strong>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.</p>

<p><strong>Methods: </strong>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.</p>

<p><strong>Results: </strong>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 &gt; C in MT-ND1, m.5317C &gt; A in MT-ND2, m.8545G &gt; A in MT-ATP8, m.9044T &gt; C in MT-ATP6 and m.15837T &gt; C in MT-CYB). In addition, we found 26 variants shared only by leprosy poles, of which two are characterized as missense (m.4248T &gt; C in MT-ND1 and m.8027G &gt; A in MT-CO2).</p>

<p><strong>Conclusion: </strong>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.</p>
  a1479-7364