The Experts below are selected from a list of 15387 Experts worldwide ranked by ideXlab platform
Jeffrey A. Canter - One of the best experts on this subject based on the ideXlab platform.
-
mitochondrial Haplogroup h and alzheimer s disease is there a connection
Neurobiology of Aging, 2009Co-Authors: Aleksandra Maruszak, Jeffrey A. Canter, Maria Styczynska, Cezary żekanowski, Maria BarcikowskaAbstract:Abstract We evaluated the involvement of the major Caucasian-specific mitochondrial Haplogroups (H, I, J, K, T, U, V, W and X), Haplogroup clusters (HV, UK, TJ, IWX) and two functional mtSNPs (4216, 4917) in the pathogenesis of Alzheimer's disease (AD) in the Polish population. The frequency distribution of mtDNA Haplogroups was non-randomly associated with APOE4 status ( χ 2 = 73.17, df = 1, p APOE4 allele influence was detected. Multivariate analysis suggested the opposite— APOE4 status could modulate the effect of mtDNA Haplogroups. We found that HV cluster is significantly associated with the risk of AD, regardless of the APOE4 status (OR = 1.59, 95% CI, 1.04–2.44, p = 0.032). Contrary to the previous studies, we report no evidence for the involvement of Haplogroup U, K, J or T in AD risk. We conclude that further analysis of subtypes of Haplogroup H would be necessary to decipher the relation of HV cluster with AD.
-
Mitochondrial Haplogroup H and Alzheimer's disease—Is there a connection?
Neurobiology of Aging, 2008Co-Authors: Aleksandra Maruszak, Jeffrey A. Canter, Maria Styczyńska, Cezary żekanowski, Maria BarcikowskaAbstract:Abstract We evaluated the involvement of the major Caucasian-specific mitochondrial Haplogroups (H, I, J, K, T, U, V, W and X), Haplogroup clusters (HV, UK, TJ, IWX) and two functional mtSNPs (4216, 4917) in the pathogenesis of Alzheimer's disease (AD) in the Polish population. The frequency distribution of mtDNA Haplogroups was non-randomly associated with APOE4 status ( χ 2 = 73.17, df = 1, p APOE4 allele influence was detected. Multivariate analysis suggested the opposite— APOE4 status could modulate the effect of mtDNA Haplogroups. We found that HV cluster is significantly associated with the risk of AD, regardless of the APOE4 status (OR = 1.59, 95% CI, 1.04–2.44, p = 0.032). Contrary to the previous studies, we report no evidence for the involvement of Haplogroup U, K, J or T in AD risk. We conclude that further analysis of subtypes of Haplogroup H would be necessary to decipher the relation of HV cluster with AD.
-
Mitochondrial Haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study.
AIDS, 2005Co-Authors: Todd Hulgan, Marylyn D. Ritchie, Gregory K. Robbins, Asha R. Kallianpur, Robert W. Shafer, Jonathan L Haines, Marshall L. Summar, David B. Clifford, David W Haas, Jeffrey A. CanterAbstract:Objective: HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define Haplogroups that may have functional implications. The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial Haplogroups. Design: Case–control study of Adult AIDS Clinical Trials Group (ACTG) study 384 and ACTG Human DNA Repository participants. Methods: ACTG study 384 was a treatment strategy trial of antiretroviral therapy with didanosine (ddI) plus stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir, or both. Subjects were followed for up to 3 years. Peripheral neuropathy was ascertained based on signs and symptoms. For this analysis, polymorphisms that define European mitochondrial Haplogroups were characterized in a majority of ACTG 384 participants, and associations with peripheral neuropathy were assessed using logistic regression. Results: A total of 509 subjects were included in this analysis of whom 250 (49%) were self-identified as white, non-Hispanic. Mitochondrial Haplogroup T was more frequent in subjects who developed peripheral neuropathy. Among 137 white subjects randomized to receive ddI plus d4T, 20.8% of those who developed peripheral neuropathy belonged to mitochondrial Haplogroup T compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval, 1.4–25.1; P = 0.009). Independent predictors of peripheral neuropathy were randomization to receive ddI plus d4T, older age, and mitochondrial Haplogroup T. Conclusions: A common European mitochondrial Haplogroup may predict NRTI-associated peripheral neuropathy. Future studies should validate this relationship, and evaluate non-European mitochondrial Haplogroups and other NRTI toxicities.
-
Mitochondrial Haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study.
AIDS, 2005Co-Authors: Todd Hulgan, Marylyn D. Ritchie, Gregory K. Robbins, Asha R. Kallianpur, Robert W. Shafer, Jonathan L Haines, Marshall L. Summar, David B. Clifford, David W Haas, Jeffrey A. CanterAbstract:Objective: HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define Haplogroups that may have functional implications. The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial Haplogroups. Design: Case–control study of Adult AIDS Clinical Trials Group (ACTG) study 384 and ACTG Human DNA Repository participants. Methods: ACTG study 384 was a treatment strategy trial of antiretroviral therapy with didanosine (ddI) plus stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir, or both. Subjects were followed for up to 3 years. Peripheral neuropathy was ascertained based on signs and symptoms. For this analysis, polymorphisms that define European mitochondrial Haplogroups were characterized in a majority of ACTG 384 participants, and associations with peripheral neuropathy were assessed using logistic regression. Results: A total of 509 subjects were included in this analysis of whom 250 (49%) were self-identified as white, non-Hispanic. Mitochondrial Haplogroup T was more frequent in subjects who developed peripheral neuropathy. Among 137 white subjects randomized to receive ddI plus d4T, 20.8% of those who developed peripheral neuropathy belonged to mitochondrial Haplogroup T compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval, 1.4–25.1; P = 0.009). Independent predictors of peripheral neuropathy were randomization to receive ddI plus d4T, older age, and mitochondrial Haplogroup T. Conclusions: A common European mitochondrial Haplogroup may predict NRTI-associated peripheral neuropathy. Future studies should validate this relationship, and evaluate non-European mitochondrial Haplogroups and other NRTI toxicities.
Douglas C. Wallace - One of the best experts on this subject based on the ideXlab platform.
-
Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle Glaucoma.
Investigative ophthalmology & visual science, 2018Co-Authors: Larry N. Singh, Jonathan G. Crowston, M. Isabel G. Lopez Sanchez, Nicole J. Van Bergen, Lisa S. Kearns, Alex W. Hewitt, Seyhan Yazar, David A. Mackey, Douglas C. Wallace, Ian A. TrounceAbstract:Purpose: To determine whether mitochondrial DNA Haplogroups or rare variants associate with primary open-angle glaucoma in subjects of European descent. Methods: A case-control comparison of age- and sex-matched cohorts of 90 primary open-angle glaucoma patients and 95 population controls. Full mitochondrial DNA sequences from peripheral blood were generated by next-generation sequencing and compared to the revised Cambridge Reference Sequence to define mitochondrial Haplogroups and variants. Results: Most subjects were of the major European Haplogroups H, J, K, U, and T. Logistic regression analysis showed Haplogroup U to be significantly underrepresented in male primary open-angle glaucoma subjects (odds ratio 0.25; 95% confidence interval [CI] 0.09-0.67; P = 0.007; Bonferroni multiple testing P = 0.022). Variants in the mitochondrial DNA gene MT-ND2 were overrepresented in the control group (P = 0.005; Bonferroni multiple testing correction P = 0.015). Conclusions: Mitochondrial DNA ancestral lineages modulate the risk for primary open-angle glaucoma in populations of European descent. Haplogroup U and rare variants in the mitochondrial DNA-encoded MT-ND2 gene may be protective against primary open-angle glaucoma. Larger studies are warranted to explore Haplogroup associations with disease risk in different ethnic groups and define biomarkers of primary open-angle glaucoma endophenotypes to target therapeutic strategies.
-
mtdna Haplogroup x an ancient link between europe western asia and north america
American Journal of Human Genetics, 1998Co-Authors: Michael D. Brown, Seyed H. Hosseini, Antonio Torroni, Hans-jürgen Bandelt, Jon C. Allen, Theodore G. Schurr, Rosaria Scozzari, Fulvio Cruciani, Douglas C. WallaceAbstract:Summary On the basis of comprehensive RFLP analysis, it has been inferred that ∼97% of Native American mtDNAs belong to one of four major founding mtDNA lineages, designated Haplogroups "A"–"D." It has been proposed that a fifth mtDNA Haplogroup (Haplogroup X) represents a minor founding lineage in Native Americans. Unlike Haplogroups A–D, Haplogroup X is also found at low frequencies in modern European populations. To investigate the origins, diversity, and continental relationships of this Haplogroup, we performed mtDNA high-resolution RFLP and complete control region (CR) sequence analysis on 22 putative Native American Haplogroup X and 14 putative European Haplogroup X mtDNAs. The results identified a consensus Haplogroup X motif that characterizes our European and Native American samples. Among Native Americans, Haplogroup X appears to be essentially restricted to northern Amerindian groups, including the Ojibwa, the Nuu-Chah-Nulth, the Sioux, and the Yakima, although we also observed this Haplogroup in the Na-Dene–speaking Navajo. Median network analysis indicated that European and Native American Haplogroup X mtDNAs, although distinct, nevertheless are distantly related to each other. Time estimates for the arrival of X in North America are 12,000–36,000 years ago, depending on the number of assumed founders, thus supporting the conclusion that the peoples harboring Haplogroup X were among the original founders of Native American populations. To date, Haplogroup X has not been unambiguously identified in Asia, raising the possibility that some Native American founders were of Caucasian ancestry.
-
mtdna diversity in chukchi and siberian eskimos implications for the genetic history of ancient beringia and the peopling of the new world
American Journal of Human Genetics, 1998Co-Authors: Yelena B Starikovskaya, Theodore G. Schurr, R I Sukernik, Andreas M Kogelnik, Douglas C. WallaceAbstract:The mtDNAs of 145 individuals representing the aboriginal populations of Chukotka-the Chukchi and Siberian Eskimos-were subjected to RFLP analysis and control-region sequencing. This analysis showed that the core of the genetic makeup of the Chukchi and Siberian Eskimos consisted of three (A, C, and D) of the four primary mtDNA haplotype groups (Haplogroups) (A-D) observed in Native Americans, with Haplogroup A being the most prevalent in both Chukotkan populations. Two unique haplotypes belonging to Haplogroup G (formerly called "other" mtDNAs) were also observed in a few Chukchi, and these have apparently been acquired through gene flow from adjacent Kamchatka, where Haplogroup G is prevalent in the Koryak and Itel'men. In addition, a 16111C-->T transition appears to delineate an "American" enclave of Haplogroup A mtDNAs in northeastern Siberia, whereas the 16192C-->T transition demarcates a "northern Pacific Rim" cluster within this Haplogroup. Furthermore, the sequence-divergence estimates for Haplogroups A, C, and D of Siberian and Native American populations indicate that the earliest inhabitants of Beringia possessed a limited number of founding mtDNA haplotypes and that the first humans expanded into the New World approximately 34,000 years before present (YBP). Subsequent migration 16,000-13,000 YBP apparently brought a restricted number of Haplogroup B haplotypes to the Americas. For millennia, Beringia may have been the repository of the respective founding sequences that selectively penetrated into northern North America from western Alaska.
-
mtDNA Haplogroup X: An Ancient Link between Europe/Western Asia and North America?
American journal of human genetics, 1998Co-Authors: Michael D. Brown, Seyed H. Hosseini, Antonio Torroni, Hans-jürgen Bandelt, Jon C. Allen, Theodore G. Schurr, Rosaria Scozzari, Fulvio Cruciani, Douglas C. WallaceAbstract:Summary On the basis of comprehensive RFLP analysis, it has been inferred that ∼97% of Native American mtDNAs belong to one of four major founding mtDNA lineages, designated Haplogroups "A"–"D." It has been proposed that a fifth mtDNA Haplogroup (Haplogroup X) represents a minor founding lineage in Native Americans. Unlike Haplogroups A–D, Haplogroup X is also found at low frequencies in modern European populations. To investigate the origins, diversity, and continental relationships of this Haplogroup, we performed mtDNA high-resolution RFLP and complete control region (CR) sequence analysis on 22 putative Native American Haplogroup X and 14 putative European Haplogroup X mtDNAs. The results identified a consensus Haplogroup X motif that characterizes our European and Native American samples. Among Native Americans, Haplogroup X appears to be essentially restricted to northern Amerindian groups, including the Ojibwa, the Nuu-Chah-Nulth, the Sioux, and the Yakima, although we also observed this Haplogroup in the Na-Dene–speaking Navajo. Median network analysis indicated that European and Native American Haplogroup X mtDNAs, although distinct, nevertheless are distantly related to each other. Time estimates for the arrival of X in North America are 12,000–36,000 years ago, depending on the number of assumed founders, thus supporting the conclusion that the peoples harboring Haplogroup X were among the original founders of Native American populations. To date, Haplogroup X has not been unambiguously identified in Asia, raising the possibility that some Native American founders were of Caucasian ancestry.
Todd Hulgan - One of the best experts on this subject based on the ideXlab platform.
-
Mitochondrial Haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study.
AIDS, 2005Co-Authors: Todd Hulgan, Marylyn D. Ritchie, Gregory K. Robbins, Asha R. Kallianpur, Robert W. Shafer, Jonathan L Haines, Marshall L. Summar, David B. Clifford, David W Haas, Jeffrey A. CanterAbstract:Objective: HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define Haplogroups that may have functional implications. The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial Haplogroups. Design: Case–control study of Adult AIDS Clinical Trials Group (ACTG) study 384 and ACTG Human DNA Repository participants. Methods: ACTG study 384 was a treatment strategy trial of antiretroviral therapy with didanosine (ddI) plus stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir, or both. Subjects were followed for up to 3 years. Peripheral neuropathy was ascertained based on signs and symptoms. For this analysis, polymorphisms that define European mitochondrial Haplogroups were characterized in a majority of ACTG 384 participants, and associations with peripheral neuropathy were assessed using logistic regression. Results: A total of 509 subjects were included in this analysis of whom 250 (49%) were self-identified as white, non-Hispanic. Mitochondrial Haplogroup T was more frequent in subjects who developed peripheral neuropathy. Among 137 white subjects randomized to receive ddI plus d4T, 20.8% of those who developed peripheral neuropathy belonged to mitochondrial Haplogroup T compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval, 1.4–25.1; P = 0.009). Independent predictors of peripheral neuropathy were randomization to receive ddI plus d4T, older age, and mitochondrial Haplogroup T. Conclusions: A common European mitochondrial Haplogroup may predict NRTI-associated peripheral neuropathy. Future studies should validate this relationship, and evaluate non-European mitochondrial Haplogroups and other NRTI toxicities.
-
Mitochondrial Haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study.
AIDS, 2005Co-Authors: Todd Hulgan, Marylyn D. Ritchie, Gregory K. Robbins, Asha R. Kallianpur, Robert W. Shafer, Jonathan L Haines, Marshall L. Summar, David B. Clifford, David W Haas, Jeffrey A. CanterAbstract:Objective: HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define Haplogroups that may have functional implications. The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial Haplogroups. Design: Case–control study of Adult AIDS Clinical Trials Group (ACTG) study 384 and ACTG Human DNA Repository participants. Methods: ACTG study 384 was a treatment strategy trial of antiretroviral therapy with didanosine (ddI) plus stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir, or both. Subjects were followed for up to 3 years. Peripheral neuropathy was ascertained based on signs and symptoms. For this analysis, polymorphisms that define European mitochondrial Haplogroups were characterized in a majority of ACTG 384 participants, and associations with peripheral neuropathy were assessed using logistic regression. Results: A total of 509 subjects were included in this analysis of whom 250 (49%) were self-identified as white, non-Hispanic. Mitochondrial Haplogroup T was more frequent in subjects who developed peripheral neuropathy. Among 137 white subjects randomized to receive ddI plus d4T, 20.8% of those who developed peripheral neuropathy belonged to mitochondrial Haplogroup T compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval, 1.4–25.1; P = 0.009). Independent predictors of peripheral neuropathy were randomization to receive ddI plus d4T, older age, and mitochondrial Haplogroup T. Conclusions: A common European mitochondrial Haplogroup may predict NRTI-associated peripheral neuropathy. Future studies should validate this relationship, and evaluate non-European mitochondrial Haplogroups and other NRTI toxicities.
David Glenn Smith - One of the best experts on this subject based on the ideXlab platform.
-
Distribution of mtDNA Haplogroup X among Native North Americans.
American journal of physical anthropology, 1999Co-Authors: David Glenn Smith, Ripan S. Malhi, Jason Eshleman, Joseph G. Lorenz, Frederika A. KaestleAbstract:Mitochondrial DNA (mtDNA) samples of 70 Native Americans, most of whom had been found not to belong to any of the four common Native American Haplogroups (A, B, C, and D), were analyzed for the presence of Dde I site losses at np 1715 and np 10394. These two mutations are characteristic of Haplogroup X which might be of European origin. The first hypervariable segment (HVSI) of the non-coding control region (CR) of mtDNA of a representative selection of samples exhibiting these mutations was sequenced to confirm their assignment to Haplogroup X. Thirty-two of the samples exhibited the restriction site losses characteristic of Haplogroup X and, when sequenced, a representative selection (n = 11) of these exhibited the CR mutations commonly associated with Haplogroup X, C --> T transitions at np 16278 and 16223, in addition to as many as three other HVSI mutations. The wide distribution of this Haplogroup throughout North America, and its prehistoric presence there, are consistent with its being a fifth founding Haplogroup exhibited by about 3% of modern Native Americans. Its markedly nonrandom distribution with high frequency in certain regions, as for the other four major mtDNA Haplogroups, should facilitate establishing ancestor/descendant relationships between modern and prehistoric groups of Native Americans. The low frequency of Haplogroups other than A, B, C, D, and X among the samples studied suggests a paucity of both recent non-Native American maternal admixture in alleged fullblood Native Americans and mutations at the restriction sites that characterize the five Haplogroups as well as the absence of additional (undiscovered) founding Haplogroups.
-
Distribution of four founding mtDNA Haplogroups among Native North Americans.
American journal of physical anthropology, 1996Co-Authors: Joseph G. Lorenz, David Glenn SmithAbstract:The mtDNA of most Native Americans has been shown to cluster into four lineages, or Haplogroups. This study provides data on the Haplogroup affiliation of nearly 500 Native North Americans including members of many tribal groups not previously studied. Phenetic cluster analysis shows a fundamental difference among 1) Eskimos and northern Na-Dene groups, which are almost exclusively mtDNA Haplogroup A, 2) tribes of the Southwest and adjacent regions, predominantly Hokan and Uto-Aztecan speakers, which lack Haplogroup A but exhibit high frequencies of Haplogroup B, 3) tribes of the Southwest and Mexico lacking only Haplogroup D, and 4) a geographically heterogeneous group of tribes which exhibit varying frequencies of all four Haplogroups. There is some correspondence between language group affiliations and the frequencies of the mtDNA Haplogroups in certain tribes, while geographic proximity appears responsible for the genetic similarity among other tribes. Other instances of similarity among tribes suggest hypotheses for testing with more detailed studies. This study also provides a context for understanding the relationships between ancient and modern populations of Native Americans.
Giuseppe Attardi - One of the best experts on this subject based on the ideXlab platform.
-
Decreased reactive oxygen species production in cells with mitochondrial Haplogroups associated with longevity.
PloS one, 2012Co-Authors: Ai Chen, Nicola Raule, Anne Chomyn, Giuseppe AttardiAbstract:Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may contribute to individual differences in function. Zhang and colleagues found a strikingly higher frequency of a C150T transition in the D-loop of mtDNA from centenarians and twins of an Italian population, and also demonstrated that this base substitution causes a remodeling of the mtDNA 151 replication origin in human leukocytes and fibroblasts [1]. The C150T transition is a polymorphism associated with several Haplogroups. To determine whether Haplogroups that carry the C150T transition display any phenotype that may be advantageous for longevity, we analyzed cybrids carrying or not the C150T transition. These cybrids were obtained by fusing cytoplasts derived from human fibroblasts with human mtDNA-less cells (ρ0 cells). We chose for cybrid construction and analysis Haplogroup-matched pairs of fibroblast strains containing or not the C150T transition. In particular, we used, as one pair of mtDNA donors, a fibroblast strain of the U3a Haplogroup, carrying the C150T transition and a strain of the U-K2 Haplogroup, without the C150T transition, and as another pair, fibroblasts of the J2b Haplogroup, carrying the C150T transition and of the J1c Haplogroup, without the C150T transition. We have found no association of respiratory capacity, mtDNA level, mitochondrial gene expression level, or growth rate with the presence of the C150T transition. However, we have found that the cybrids with Haplogroups that include the C150T transition have in common a lower reactive oxygen species (ROS) production rate than the Haplogroup-matched cybrids without that transition. Thus, the lower ROS production rate may be a factor in the increased longevity associated with the U and the J2 Haplogroups. Of further interest, we found that cybrids with the U3a Haplogroup exhibited a higher respiration rate than the other cybrids examined.
