title: Mitochondrial genome variations in advanced stage endometriosis: a study in South Indian population.
abstract: BACKGROUND
  Endometriosis is a chronic gynecological benign disease that shares several features similar to malignancy. Mitochondrial DNA (mtDNA) mutations have been reported in all most all types of tumors. However, it is not known as to whether mtDNA mutations are associated with endometriosis.
  
  
  METHODS
  We sequenced the entire mitochondrial genome of analogous ectopic and eutopic endometrial tissues along with blood samples from 32 advanced stage endometriosis patients to analyze the role of somatic and germ-line mtDNA variations in pathogenesis of endometriosis. All ectopic tissues were screened for tumor-specific mtDNA deletions and microsatellite instability (MSI). We also performed mtDNA haplogrouping in 128 patients and 90 controls to identify its possible association with endometriosis risk.
  
  
  RESULTS
  We identified 51 somatic (novel: 31; reported: 20) and 583 germ-line mtDNA variations (novel: 53; reported: 530) in endometriosis patients. The A13603G, a novel missense mutation which leads to a substitution from serine to glycine at the codon 423 of ND5 gene showed 100% incidence in ectopic tissues. Interestingly, eutopic endometrium and peripheral leukocytes of all the patients showed heteroplasmy (A/G; 40-80%) at this locus, while their ectopic endometrium showed homoplasmic mutant allele (G/G). Superimposition of native and mutant structures of ND5 generated by homology modeling revealed no structural differences. Tumor-specific deletions and MSI were not observed in any of the ectopic tissues. Haplogrouping analysis showed a significant association between haplogroup M5 and endometriosis risk (P: 0.00069) after bonferroni correction.
  
  
  CONCLUSIONS
  Our findings substantiate the rationale for exploring the mitochondrial genome as a biomarker for the diagnosis of endometriosis.
authors: Department of Biochemistry, Osmania University, Hyderabad, Andhra Pradesh, India.
authors: Suresh
authors: S
authors: Govatati
authors: Nageswara Rao
authors: NR
authors: Tipirisetti
authors: Shyam
authors: S
authors: Perugu
authors: Vijaya Lakshmi
authors: VL
authors: Kodati
authors: Mamata
authors: M
authors: Deenadayal
authors: Vishnupriya
authors: V
authors: Satti
authors: Manjula
authors: M
authors: Bhanoori
authors: S
authors: S
authors: Shivaji
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000737:chemistry / Q000235:genetics; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D054629:Genome, Mitochondrial / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D053842:Microsatellite Instability; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009367:Neoplasm Staging
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I