The search of ‘novel’ mtDNA mutations in hypertrophic cardiomyopathy: MITOMAPping as a risk factor

Bandelt, Hans‐Jürgen; Yao, Yong‐Gang; Salas, Antonio

doi:10.1016/j.ijcard.2007.02.049

Cited by 20 publications

(21 citation statements)

References 38 publications

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“…Although mtDNA mutations may be an underlying mechanism for developing schizophrenia, few studies have succeeded in attributing mtDNA variants to the risk of schizophrenia; in the cases where such associations were found, the results could not be replicated [Lindholm et al, 1997;Odawara et al, 1998;Gentry and Nimgaonkar 2000;Kazuno et al, 2005;Martorell et al, 2006;Bamne et al, 2008;Rollins et al, 2009;Ueno et al, 2009;Ichikawa et al, 2012;Sequeira et al, 2012]. As often observed in medical literature, most of these studies claimed to identify new variants; however, most of these variants had been previously identified in control subjects and incorporated into different databases (e.g., Mitomap; http://www.mitomap.org/ MITOMAP) [Bandelt et al, 2006[Bandelt et al, , 2008[Bandelt et al, , 2009. One explanation for the failure to identify changes in the mtDNA of schizophrenia patients might be the presence of tissue-specific mutations.…”

Section: Discussion Sequencing Analyses Of Mtdna In Maternal Schizophmentioning

confidence: 99%

Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia

Torrell

Salas

Abasolo

et al. 2014

American J of Med Genetics Pt B

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It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia.

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Section: Discussion Sequencing Analyses Of Mtdna In Maternal Schizophmentioning

confidence: 99%

Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia

Torrell

Salas

Abasolo

et al. 2014

American J of Med Genetics Pt B

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“…In any case, the strategy would be to screen PhyloTree for the mutational variants characterizing the sequence of interest and using the tools available in the preferred Web browser. The search strategies proposed here extend those previously used in [14,15] for finding articles in which certain mtDNA mutations were mentioned; see Table 1.…”

Section: Haplogroupingmentioning

confidence: 99%

Haplogrouping mitochondrial DNA sequences in Legal Medicine/Forensic Genetics

2012

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Haplogrouping refers to the classification of (partial) mitochondrial DNA (mtDNA) sequences into haplogroups using the current knowledge of the worldwide mtDNA phylogeny. Haplogroup assignment of mtDNA control-region sequences assists in the focused comparison with closely related complete mtDNA sequences and thus serves two main goals in forensic genetics: first is the a posteriori quality analysis of sequencing results and second is the prediction of relevant coding-region sites for confirmation or further refinement of haplogroup status. The latter may be important in forensic casework where discrimination power needs to be as high as possible. However, most articles published in forensic genetics perform haplogrouping only in a rudimentary or incorrect way. The present study features PhyloTree as the key tool for assigning control-region sequences to haplogroups and elaborates on additional Web-based searches for finding near-matches with complete mtDNA genomes in the databases. In contrast, none of the automated haplogrouping tools available can yet compete with manual haplogrouping using PhyloTree plus additional Web-based searches, especially when confronted with artificial recombinants still present in forensic mtDNA datasets. We review and classify the various attempts at haplogrouping by using a multiplex approach or relying on automated haplogrouping. Furthermore, we re-examine a few articles in forensic journals providing mtDNA population data where appropriate haplogrouping following PhyloTree immediately highlights several kinds of sequence errors.

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“…This variation was initially associated with a rare variety of hypertrophic cardiomyopathy in a 65-year-old Indian patient, 21 but subsequently suggested to be a polymorphism associated with the M5a haplogroup. 22 The second complex I variation, m.4160T4C missense variation in the MTND1 gene, has been reported several times before [23][24][25] and has been associated with LHON and the related neurological abnormalities involved. This variation substitutes a highly conserved amino-acid residue for another with the same polarity (p.Leu285Pro) and in silico analyses predicts it to have a detrimental impact.…”

Section: Non-haplogroup-associated Mtdna Variantsmentioning

confidence: 99%

Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease

et al. 2012

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Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by the diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in the muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81 ± 26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup-defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full-length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.

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The search of ‘novel’ mtDNA mutations in hypertrophic cardiomyopathy: MITOMAPping as a risk factor

Cited by 20 publications

References 38 publications

Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia

Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia

Haplogrouping mitochondrial DNA sequences in Legal Medicine/Forensic Genetics

Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease

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