The Experts below are selected from a list of 1461 Experts worldwide ranked by ideXlab platform

Jianxin Lu - One of the best experts on this subject based on the ideXlab platform.

  • the trna gly t10003c mutation in Mitochondrial Haplogroup m11b in a chinese family with diabetes decreases the steady state level of trna gly increases aberrant reactive oxygen species production and reduces Mitochondrial membrane potential
    Molecular and Cellular Biochemistry, 2015
    Co-Authors: Wei Li, Weixing Li, Hailing Wang, Xiaomin Guan, Wanlin Zhang, Wei Ye, Jianxin Lu
    Abstract:

    Mitochondrial diabetes originates mainly from mutations located in maternally transmitted, Mitochondrial tRNA-coding genes. In a genetic screening program of type 2 diabetes conducted with a Chinese Han population, we found one family with suggestive maternally transmitted diabetes. The proband’s Mitochondrial genome was analyzed using DNA sequencing. Total 42 known nucleoside changes and 1 novel variant were identified, and the entire Mitochondrial DNA sequence was assigned to Haplogroup M11b. Phylogenetic analysis showed that a homoplasmic mutation, 10003T>C transition, occurred at the highly conserved site in the gene encoding tRNAGly. Using a transMitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNAGly significantly affected and the amount of tRNAGly decreased by 97 %, production of reactive oxygen species was enhanced, and Mitochondrial membrane potential, mtDNA copy number and cellular oxygen consumption rate were remarkably decreased compared with wild-type cybrid cells. The homoplasmic 10003T>C mutation in the Mitochondrial tRNAGly gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family.

  • the 12s rrna a1555g mutation in the Mitochondrial Haplogroup d5a is responsible for maternally inherited hypertension and hearing loss in two chinese pedigrees
    European Journal of Human Genetics, 2012
    Co-Authors: Hong Chen, Zhongqiu Lu, Yanzi Meng, Yan Wang, Jun Qin Mo, Jing Zheng, Bingjiao Zheng, Fang Fang, Pingping Jiang, Jianxin Lu
    Abstract:

    We reported here clinical, genetic evaluations and molecular analysis of Mitochondrial DNA (mtDNA) in two Han Chinese families carrying the known Mitochondrial 12S rRNA A1555G mutation. In contrast with the previous data that hearing loss as a sole phenotype was present in the maternal lineage of other families carrying the A1555G mutation, matrilineal relatives among these two Chinese families exhibited both hearing loss and hypertension. Of 21 matrilineal relatives, 9 subjects exhibited both hearing loss and hypertension, 2 individuals suffered from only hypertension and 1 member had only hearing loss. The average age at onset of hypertension in the affected matrilineal relatives of these families was 60 and 46 years, respectively, whereas those of hearing loss in these two families were 33 and 55 years, respectively. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian Haplogroup D5a. In contrast, the A1555G mutation occurred among other mtDNA Haplogroups D, B, R, F, G, Y, M and N, respectively. Our data further support that the A1555G mutation is necessary but by itself insufficient to produce the clinical phenotype. The other modifiers are responsible for the phenotypic variability of matrilineal relatives within and among these families carrying the A1555G mutation. Our investigation provides the first evidence that the 12S rRNA A1555G mutation leads to both of hearing loss and hypertension. Thus, our findings may provide the new insights into the understanding of pathophysiology and valuable information for management and treatment of maternally inherited hearing loss and hypertension.

Dana C Crawford - One of the best experts on this subject based on the ideXlab platform.

  • hi mc a novel method for high throughput Mitochondrial Haplogroup classification
    PeerJ, 2018
    Co-Authors: Sandra Smieszek, Sabrina L Mitchell, Olivia J Veatch, Robert J Goodloe, Quinn S Wells, Deborah G Murdock, Eric Farbereger, Nicholas R Wheeler, Dana C Crawford
    Abstract:

    : Effective approaches for assessing Mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial Haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for Mitochondrial Haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for Mitochondrial Haplogroup classification that is cost effective and applicable to large sample sizes making Mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms that allows for accurate classification of European, African, and Native American Mitochondrial Haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. Hi-MC is available in the CRAN repository and the source code is freely available at https://github.com/vserch/himc.

  • Hi-MC: A novel method for high-throughput Mitochondrial Haplogroup classification
    2017
    Co-Authors: Sabrina L Mitchell, Eric H Farber-eger, Olivia J Veatch, Robert J Goodloe, Quinn S Wells, Deborah G Murdock, Dana C Crawford
    Abstract:

    Effective approaches for assessing Mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial Haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for Mitochondrial Haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for Mitochondrial Haplogroup classification that is cost effective and applicable to large sample sizes making Mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms (SNPs) that allows for accurate classification of European, African, and Native American Mitochondrial Haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. The source code is freely available at https://github.com/vserch/himc .

  • Characterization of Mitochondrial Haplogroups in a large population-based sample from the United States
    Human Genetics, 2014
    Co-Authors: Sabrina L Mitchell, Deborah G Murdock, Robert Goodloe, Kristin Brown-gentry, Sarah A. Pendergrass, Dana C Crawford
    Abstract:

    Mitochondrial DNA (mtDNA) Haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian Mitochondrial Haplogroup lineages. Using these mtDNA markers, we constructed a Mitochondrial Haplogroup classification tree and classified 18,832 participants from the National Health and Nutrition Examination Surveys (NHANES). To our knowledge, this is the largest study to date characterizing Mitochondrial Haplogroups in a population-based sample from the United States, and the first study characterizing Mitochondrial Haplogroup distributions in self-identified Mexican Americans separately from Hispanic Americans of other descent. We observed clear differences in the distribution of maternal genetic ancestry consistent with proposed admixture models for these subpopulations, underscoring the genetic heterogeneity of the United States Hispanic population. The Mitochondrial Haplogroup distributions in the other self-identified racial/ethnic groups within NHANES were largely comparable to previous studies. Mitochondrial Haplogroup classification was highly concordant with self-identified race/ethnicity (SIRE) in non-Hispanic whites (94.8 %), but was considerably lower in admixed populations including non-Hispanic blacks (88.3 %), Mexican Americans (81.8 %), and other Hispanics (61.6 %), suggesting SIRE does not accurately reflect maternal genetic ancestry, particularly in populations with greater proportions of admixture. Thus, it is important to consider inconsistencies between SIRE and genetic ancestry when performing genetic association studies. The Mitochondrial Haplogroup data that we have generated, coupled with the epidemiologic variables in NHANES, is a valuable resource for future studies investigating the contribution of mtDNA variation to human health and disease.

Joan M Obrien - One of the best experts on this subject based on the ideXlab platform.

  • Mitochondrial Haplogroup l1c2 is associated with increased disease severity in african american patients with primary open angle glaucoma
    Journal of Clinical & Experimental Ophthalmology, 2019
    Co-Authors: Meera Ramakrishnan, Harini V Gudiseva, David W Collins, Maxwell Pistilli, Venkata M Chavali, Amanda Lehman, Victoria Addis, Joan M Obrien
    Abstract:

    Objective: The purpose of this study is to evaluate the role Mitochondrial inheritance plays in primary open-angle glaucoma (POAG) characteristics in African Americans. Methods: POAG cases from the L1c2 and L1b Mitochondrial Haplogroups were compared in a retrospective case-case study. Twenty-six pairs of self-identified African American POAG cases from L1c2 and L1b Mitochondrial Haplogroups matched on age (mean [SD] = 71.2 [9.6] and 71.3 [9.6] years, respectively; p = 0.97), sex (21 female and 5 male pairs), and family history of glaucoma (positive in 15/26 [58%] pairs) were included. Results: L1c2 subjects displayed higher vertical cup-to-disc ratio (0.75 [0.12] and 0.67 [0.16], respectively; p = 0.01, Bonferroni-corrected p = 0.08), worse pattern standard deviation on visual field (VF) testing (5.5 [3.5] and 3.5 [2.7]; p = 0.005, Bonferroni-corrected p = 0.02), and more severe glaucoma based on American Glaucoma Society staging criteria (p = 0.04, Bonferroni-corrected p = 0.32) compared to L1b subjects. L1c2 also trended towards worse mean deviation on VF compared to L1b (-8.2 [7.6] and -5.8 [6.8], respectively, p = 0.17). Best corrected visual acuity, central corneal thickness, maximum intraocular pressure (IOP), and cataract severity were comparable between L1c2 and L1b Haplogroups (p ≥ 0.49), as was retinal nerve fiber layer thickness on optical coherence tomography (75.1 [14.1] and 75.1 [13.0]; p = 0.99). Conclusion: Results demonstrated worse glaucomatous cupping and more severe VF loss in the L1c2 compared to the L1b Haplogroup despite comparable IOP. Findings implicate Mitochondrial inheritance as a factor affecting POAG severity and may ultimately contribute to stratifying POAG patients into phenotypically and genotypically distinct subgroups.

Sabrina L Mitchell - One of the best experts on this subject based on the ideXlab platform.

  • hi mc a novel method for high throughput Mitochondrial Haplogroup classification
    PeerJ, 2018
    Co-Authors: Sandra Smieszek, Sabrina L Mitchell, Olivia J Veatch, Robert J Goodloe, Quinn S Wells, Deborah G Murdock, Eric Farbereger, Nicholas R Wheeler, Dana C Crawford
    Abstract:

    : Effective approaches for assessing Mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial Haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for Mitochondrial Haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for Mitochondrial Haplogroup classification that is cost effective and applicable to large sample sizes making Mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms that allows for accurate classification of European, African, and Native American Mitochondrial Haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. Hi-MC is available in the CRAN repository and the source code is freely available at https://github.com/vserch/himc.

  • Hi-MC: A novel method for high-throughput Mitochondrial Haplogroup classification
    2017
    Co-Authors: Sabrina L Mitchell, Eric H Farber-eger, Olivia J Veatch, Robert J Goodloe, Quinn S Wells, Deborah G Murdock, Dana C Crawford
    Abstract:

    Effective approaches for assessing Mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial Haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for Mitochondrial Haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for Mitochondrial Haplogroup classification that is cost effective and applicable to large sample sizes making Mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms (SNPs) that allows for accurate classification of European, African, and Native American Mitochondrial Haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. The source code is freely available at https://github.com/vserch/himc .

  • Characterization of Mitochondrial Haplogroups in a large population-based sample from the United States
    Human Genetics, 2014
    Co-Authors: Sabrina L Mitchell, Deborah G Murdock, Robert Goodloe, Kristin Brown-gentry, Sarah A. Pendergrass, Dana C Crawford
    Abstract:

    Mitochondrial DNA (mtDNA) Haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian Mitochondrial Haplogroup lineages. Using these mtDNA markers, we constructed a Mitochondrial Haplogroup classification tree and classified 18,832 participants from the National Health and Nutrition Examination Surveys (NHANES). To our knowledge, this is the largest study to date characterizing Mitochondrial Haplogroups in a population-based sample from the United States, and the first study characterizing Mitochondrial Haplogroup distributions in self-identified Mexican Americans separately from Hispanic Americans of other descent. We observed clear differences in the distribution of maternal genetic ancestry consistent with proposed admixture models for these subpopulations, underscoring the genetic heterogeneity of the United States Hispanic population. The Mitochondrial Haplogroup distributions in the other self-identified racial/ethnic groups within NHANES were largely comparable to previous studies. Mitochondrial Haplogroup classification was highly concordant with self-identified race/ethnicity (SIRE) in non-Hispanic whites (94.8 %), but was considerably lower in admixed populations including non-Hispanic blacks (88.3 %), Mexican Americans (81.8 %), and other Hispanics (61.6 %), suggesting SIRE does not accurately reflect maternal genetic ancestry, particularly in populations with greater proportions of admixture. Thus, it is important to consider inconsistencies between SIRE and genetic ancestry when performing genetic association studies. The Mitochondrial Haplogroup data that we have generated, coupled with the epidemiologic variables in NHANES, is a valuable resource for future studies investigating the contribution of mtDNA variation to human health and disease.

Nicole Weisschuh - One of the best experts on this subject based on the ideXlab platform.