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Sample records for eurasian mitochondrial haplogroups

  1. Mitochondrial haplogroup C in ancient mitochondrial DNA from Ukraine extends the presence of East Eurasian genetic lineages in Neolithic Central and Eastern Europe.

    PubMed

    Nikitin, Alexey G; Newton, Jeremy R; Potekhina, Inna D

    2012-09-01

    Recent studies of ancient mitochondrial DNA (mtDNA) lineages have revealed the presence of East Eurasian mtDNA haplogroups in the Central European Neolithic. Here we report the finding of East Eurasian lineages in ancient mtDNA from two Neolithic cemeteries of the North Pontic Region (NPR) in Ukraine. In our study, comprehensive haplotyping information was obtained for 7 out of 18 specimens. Although the majority of identified mtDNA haplogroups belonged to the traditional West Eurasian lineages of H and U, three specimens were determined to belong to the lineages of mtDNA haplogroup C. This find extends the presence of East Eurasian lineages in Neolithic Europe from the Carpathian Mountains to the northern shores of the Black Sea and provides the first genetic account of Neolithic mtDNA lineages from the NPR. PMID:22673688

  2. Complete Mitochondrial DNA Analysis of Eastern Eurasian Haplogroups Rarely Found in Populations of Northern Asia and Eastern Europe

    PubMed Central

    Derenko, Miroslava; Malyarchuk, Boris; Denisova, Galina; Perkova, Maria; Rogalla, Urszula; Grzybowski, Tomasz; Khusnutdinova, Elza; Dambueva, Irina; Zakharov, Ilia

    2012-01-01

    With the aim of uncovering all of the most basal variation in the northern Asian mitochondrial DNA (mtDNA) haplogroups, we have analyzed mtDNA control region and coding region sequence variation in 98 Altaian Kazakhs from southern Siberia and 149 Barghuts from Inner Mongolia, China. Both populations exhibit the prevalence of eastern Eurasian lineages accounting for 91.9% in Barghuts and 60.2% in Altaian Kazakhs. The strong affinity of Altaian Kazakhs and populations of northern and central Asia has been revealed, reflecting both influences of central Asian inhabitants and essential genetic interaction with the Altai region indigenous populations. Statistical analyses data demonstrate a close positioning of all Mongolic-speaking populations (Mongolians, Buryats, Khamnigans, Kalmyks as well as Barghuts studied here) and Turkic-speaking Sojots, thus suggesting their origin from a common maternal ancestral gene pool. In order to achieve a thorough coverage of DNA lineages revealed in the northern Asian matrilineal gene pool, we have completely sequenced the mtDNA of 55 samples representing haplogroups R11b, B4, B5, F2, M9, M10, M11, M13, N9a and R9c1, which were pinpointed from a massive collection (over 5000 individuals) of northern and eastern Asian, as well as European control region mtDNA sequences. Applying the newly updated mtDNA tree to the previously reported northern Asian and eastern Asian mtDNA data sets has resolved the status of the poorly classified mtDNA types and allowed us to obtain the coalescence age estimates of the nodes of interest using different calibrated rates. Our findings confirm our previous conclusion that northern Asian maternal gene pool consists of predominantly post-LGM components of eastern Asian ancestry, though some genetic lineages may have a pre-LGM/LGM origin. PMID:22363811

  3. Mutation Rate Switch inside Eurasian Mitochondrial Haplogroups: Impact of Selection and Consequences for Dating Settlement in Europe

    PubMed Central

    Pierron, Denis; Chang, Ivan; Arachiche, Amal; Heiske, Margit; Thomas, Olivier; Borlin, Marine; Pennarun, Erwan; Murail, Pacal; Thoraval, Didier; Rocher, Christophe; Letellier, Thierry

    2011-01-01

    R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America). This lineage played a major role in migration “out of Africa” and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years, as well as several limitations of standard dating methods, likely to lead to false interpretations. These findings highlight the association of a striking under-accumulation of synonymous mutations, an over-accumulation of non-synonymous mutations, and the phenotypic effect on haplogroup J. Consequently, haplogroup J is apparently not a Neolithic group but an older haplogroup (Paleolithic) that was subjected to an underestimated selective force. These findings also indicated an under-accumulation of synonymous and non-synonymous mutations localized on coding and non-coding (HVS1) sequences for haplogroup R0, which contains the major haplogroups H and V. These new dates are likely to impact the present colonization model for Europe and confirm the late glacial resettlement scenario. PMID:21738700

  4. The history of the North African mitochondrial DNA haplogroup U6 gene flow into the African, Eurasian and American continents

    PubMed Central

    2014-01-01

    Background Complete mitochondrial DNA (mtDNA) genome analyses have greatly improved the phylogeny and phylogeography of human mtDNA. Human mitochondrial DNA haplogroup U6 has been considered as a molecular signal of a Paleolithic return to North Africa of modern humans from southwestern Asia. Results Using 230 complete sequences we have refined the U6 phylogeny, and improved the phylogeographic information by the analysis of 761 partial sequences. This approach provides chronological limits for its arrival to Africa, followed by its spreads there according to climatic fluctuations, and its secondary prehistoric and historic migrations out of Africa colonizing Europe, the Canary Islands and the American Continent. Conclusions The U6 expansions and contractions inside Africa faithfully reflect the climatic fluctuations that occurred in this Continent affecting also the Canary Islands. Mediterranean contacts drove these lineages to Europe, at least since the Neolithic. In turn, the European colonization brought different U6 lineages throughout the American Continent leaving the specific sign of the colonizers origin. PMID:24885141

  5. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    PubMed

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed; Erzurum, Serpil C; Aldred, Micheala A

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  6. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension

    PubMed Central

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  7. Association between mitochondrial DNA haplogroup and myelodysplastic syndromes.

    PubMed

    Poynter, Jenny N; Richardson, Michaela; Langer, Erica; Hooten, Anthony J; Roesler, Michelle; Hirsch, Betsy; Nguyen, Phuong L; Cioc, Adina; Warlick, Erica; Ross, Julie A

    2016-09-01

    Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non-Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS-R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population-based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc. PMID:27121678

  8. Mitochondrial DNA haplogroups may influence Fabry disease phenotype.

    PubMed

    Simoncini, C; Chico, L; Concolino, D; Sestito, S; Fancellu, L; Boadu, W; Sechi, G P; Feliciani, C; Gnarra, M; Zampetti, A; Salviati, A; Scarpelli, M; Orsucci, D; Bonuccelli, U; Siciliano, G; Mancuso, M

    2016-08-26

    While the genetic origin of Fabry disease (FD) is well known, it is still unclear why the disease presents a wide heterogeneity of clinical presentation and progression, even within the same family. Emerging observations reveal that mitochondrial impairment and oxidative stress may be implicated in the pathogenesis of FD. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of FD, we have genotyped European mtDNA haplogroups in 77 Italian FD patients and 151 healthy controls. Haplogroups H and I, and haplogroup cluster HV were significantly more frequent in patients than controls. However, no correlation with gender, age of onset, organ involvement was observed. Our study seems to provide some evidence of a contribution of mitochondrial variation in FD pathogenesis, at least in Italy. PMID:27365132

  9. Traces of early Eurasians in the Mansi of northwest Siberia revealed by mitochondrial DNA analysis.

    PubMed

    Derbeneva, Olga A; Starikovskaya, Elena B; Wallace, Douglas C; Sukernik, Rem I

    2002-04-01

    The mitochondrial DNA (mtDNA) of 98 Mansi, an ancient group (formerly known as "Vogul") of Uralic-speaking fishers and hunters on the eastern slope of the northern Ural Mountains, were analyzed for sequence variants by restriction fragment--length polymorphism analysis, control-region sequencing, and sequencing of additional informative sites in the coding region. Although 63.3% of the mtDNA detected in the Mansi falls into western Eurasian lineages (e.g., haplogroups UK, TJ, and HV), the remaining 36.7% encompass a subset of eastern Eurasian lineages (e.g., haplogroups A, C, D, F, G, and M). Among the western Eurasian lineages, subhaplogroup U4 was found at a remarkable frequency of 16.3%, along with lineages U5, U7, and J2. This suggests that the aboriginal populations residing immediately to the east of the Ural Mountains may encompass remnants of the early Upper Paleolithic expansion from the Middle East/southeastern Europe. The added presence of eastern Eurasian mtDNA lineages in the Mansi introduces the possibilities that proto-Eurasians encompassed a range of macrohaplogroup M and N lineages that subsequently became geographically distributed and that the Paleolithic expansion may have reached this part of Siberia before it split into western and eastern human groups. PMID:11845409

  10. Mitochondrial DNA haplogroups modify the risk of osteoarthritis by altering mitochondrial function and intracellular mitochondrial signals.

    PubMed

    Fang, Hezhi; Zhang, Fengjiao; Li, Fengjie; Shi, Hao; Ma, Lin; Du, Miaomiao; You, Yanting; Qiu, Ruyi; Nie, Hezhongrong; Shen, Lijun; Bai, Yidong; Lyu, Jianxin

    2016-04-01

    Haplogroup G predisposes one to an increased risk of osteoarthritis (OA) occurrence, while haplogroup B4 is a protective factor against OA onset. However, the underlying mechanism is not known. Here, by using trans-mitochondrial technology, we demonstrate that the activity levels of mitochondrial respiratory chain complex I and III are higher in G cybrids than in haplogroup B4. Increased mitochondrial oxidative phosphorylation (OXPHOS) promotes mitochondrial-related ATP generation in G cybrids, thereby shifting the ATP generation from glycolysis to OXPHOS. Furthermore, we found that lower glycolysis in G cybrids decreased cell viability under hypoxia (1% O2) compared with B4 cybrids. In contrast, G cybrids have a lower NAD(+)/NADH ratio and less generation of reactive oxygen species (ROS) under both hypoxic (1% O2) and normoxic (20% O2) conditions than B4 cybrids, indicating that mitochondrial-mediated signaling pathways (retrograde signaling) differ between these cybrids. Gene expression profiling of G and B4 cybrids using next-generation sequencing technology showed that 404 of 575 differentially expressed genes (DEGs) between G and B4 cybrids are enriched in 17 pathways, of which 11 pathways participate in OA. Quantitative reverse transcription PCR (qRT-PCR) analyses confirmed that G cybrids had lower glycolysis activity than B4 cybrids. In addition, we confirmed that the rheumatoid arthritis pathway was over-activated in G cybrids, although the remaining 9 pathways were not further tested by qRT-PCR. In conclusion, our findings indicate that mtDNA haplogroup G may increase the risk of OA by shifting the metabolic profile from glycolysis to OXPHOS and by over-activating OA-related signaling pathways. PMID:26705675

  11. Sephardic signature in haplogroup T mitochondrial DNA

    PubMed Central

    Bedford, Felice L

    2012-01-01

    A rare combination of mutations within mitochondrial DNA subhaplogroup T2e is identified as affiliated with Sephardic Jews, a group that has received relatively little attention. Four investigations were pursued: Search of the motif in 250 000 control region records across 8 databases, comparison of frequencies of T subhaplogroups (T1, T2b, T2c, T2e, T4, T*) across 11 diverse populations, creation of a phylogenic median-joining network from public T2e control region entries, and analysis of one Sephardic mitochondrial full genomic sequence with the motif. It was found that the rare motif belonged only to Sephardic descendents (Turkey, Bulgaria), to inhabitants of North American regions known for secret Spanish–Jewish colonization, or were consistent with Sephardic ancestry. The incidence of subhaplogroup T2e decreased from the Western Arabian Peninsula to Italy to Spain and into Western Europe. The ratio of sister subhaplogroups T2e to T2b was found to vary 40-fold across populations from a low in the British Isles to a high in Saudi Arabia with the ratio in Sephardim more similar to Saudi Arabia, Egypt, and Italy than to hosts Spain and Portugal. Coding region mutations of 2308G and 14499T may locate the Sephardic signature within T2e, but additional samples and reworking of current T2e phylogenetic branch structure is needed. The Sephardic Turkish community has a less pronounced founder effect than some Ashkenazi groups considered singly (eg, Polish), but other comparisons of interest await comparable averaging. Registries of signatures will benefit the study of populations with a large number of smaller-size founders. PMID:22108605

  12. Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

    PubMed Central

    Yunis, Juan J.; Yunis, Emilio J.

    2013-01-01

    The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest. PMID:24130438

  13. Mitochondrial Haplogroups Modify the Risk of Developing Hypertrophic Cardiomyopathy in a Danish Population

    PubMed Central

    Hagen, Christian M.; Aidt, Frederik H.; Hedley, Paula L.; Jensen, Morten K.; Havndrup, Ole; Kanters, Jørgen K.; Moolman-Smook, Johanna C.; Larsen, Severin O.; Bundgaard, Henning; Christiansen, Michael

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from blood, was sequenced and haplogroups identified in 91 probands with HCM. The association with HCM was ascertained using two Danish control populations. Haplogroup H was more prevalent in HCM patients, 60% versus 46% (p = 0.006) and 41% (p = 0.003), in the two control populations. Haplogroup J was less prevalent, 3% vs. 12.4% (p = 0.017) and 9.1%, (p = 0.06). Likewise, the UK haplogroup cluster was less prevalent in HCM, 11% vs. 22.1% (p = 0.02) and 22.8% (p = 0.04). These results indicate that haplogroup H constitutes a susceptibility factor and that haplogroup J and haplogroup cluster UK are protective factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy suggests that mtDNA haplotypes may be of significance in determining whether a physiological hypertrophy develops into myopathy. mtDNA haplotypes may have the potential of becoming significant biomarkers in cardiomyopathy. PMID:23940792

  14. Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

    PubMed Central

    Chen, Ya-Fang; Chen, Wan-Jin; Lin, Xiao-Zhen; Zhang, Qi-Jie; Cai, Jiang-Ping; Liou, Chia-Wei; Wang, Ning

    2015-01-01

    Background: Mitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Methods: Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population. Results: Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082–0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030–0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112–11.523, P = 0.033), other haplogroups also did not show significant differences in the group. Conclusions: Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese. PMID:26112715

  15. Neolithic mitochondrial haplogroup H genomes and the genetic origins of Europeans.

    PubMed

    Brotherton, Paul; Haak, Wolfgang; Templeton, Jennifer; Brandt, Guido; Soubrier, Julien; Jane Adler, Christina; Richards, Stephen M; Sarkissian, Clio Der; Ganslmeier, Robert; Friederich, Susanne; Dresely, Veit; van Oven, Mannis; Kenyon, Rosalie; Van der Hoek, Mark B; Korlach, Jonas; Luong, Khai; Ho, Simon Y W; Quintana-Murci, Lluis; Behar, Doron M; Meller, Harald; Alt, Kurt W; Cooper, Alan; Adhikarla, Syama; Ganesh Prasad, Arun Kumar; Pitchappan, Ramasamy; Varatharajan Santhakumari, Arun; Balanovska, Elena; Balanovsky, Oleg; Bertranpetit, Jaume; Comas, David; Martínez-Cruz, Begoña; Melé, Marta; Clarke, Andrew C; Matisoo-Smith, Elizabeth A; Dulik, Matthew C; Gaieski, Jill B; Owings, Amanda C; Schurr, Theodore G; Vilar, Miguel G; Hobbs, Angela; Soodyall, Himla; Javed, Asif; Parida, Laxmi; Platt, Daniel E; Royyuru, Ajay K; Jin, Li; Li, Shilin; Kaplan, Matthew E; Merchant, Nirav C; John Mitchell, R; Renfrew, Colin; Lacerda, Daniela R; Santos, Fabrício R; Soria Hernanz, David F; Spencer Wells, R; Swamikrishnan, Pandikumar; Tyler-Smith, Chris; Paulo Vieira, Pedro; Ziegle, Janet S

    2013-01-01

    Haplogroup H dominates present-day Western European mitochondrial DNA variability (>40%), yet was less common (~19%) among Early Neolithic farmers (~5450 BC) and virtually absent in Mesolithic hunter-gatherers. Here we investigate this major component of the maternal population history of modern Europeans and sequence 39 complete haplogroup H mitochondrial genomes from ancient human remains. We then compare this 'real-time' genetic data with cultural changes taking place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. Our results reveal that the current diversity and distribution of haplogroup H were largely established by the Mid Neolithic (~4000 BC), but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers expanding out of Iberia in the Late Neolithic (~2800 BC). Dated haplogroup H genomes allow us to reconstruct the recent evolutionary history of haplogroup H and reveal a mutation rate 45% higher than current estimates for human mitochondria. PMID:23612305

  16. Characterization of mitochondrial haplogroups in a large population-based sample from the United States.

    PubMed

    Mitchell, Sabrina L; Goodloe, Robert; Brown-Gentry, Kristin; Pendergrass, Sarah A; Murdock, Deborah G; Crawford, Dana C

    2014-07-01

    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. PMID:24488180

  17. Analysis of mitochondrial haplogroups associated with TTR Val30Ala familial amyloidotic polyneuropathy in Chinese patients.

    PubMed

    Liu, Jing-Yao; Jiang, Xin-Mei; Zhang, Min; Guo, Ying-Jie

    2012-12-01

    Extracellular deposition of abnormal transthyretin (TTR) amyloid fibrils leads to familial amyloidotic polyneuropathy (FAP), an inherited autsomal dominant disease. A large number of protein variants, each caused by a different point mutation in the TTR gene have been identified, including TTR Val30Ala. Since the age of onset, organ involvement, and disease progression are highly variable in FAP, even among individuals with the same TTR genetic variation. it is likely that other genetic and environmental factors influence FAP disease phenotype. One study has found a relationship between mitochondrial haplogroups and age of onset of FAP. In this study, we wondered whether certain mitochondrial haplogroups were associated with the cases of TTR Val30Ala FAP in a Chinese population. Mitochondrial haplogroup analysis was performed on a group of patients and their relatives and on a group of healthy controls. All FAP probands were unrelated in their maternal lineages. The chi-squared test for independence found no difference in mitochondrial haplogroup distribution between FAP and control groups. This is the first study reporting frequency and distribution of different haplogroups in FAP in a Chinese population. Although the study group was small, TTR Val30Ala FAP in China seems unrelated to mitochondrial haplogroup. PMID:22784244

  18. Mitochondrial DNA of ancient Cumanians: culturally Asian steppe nomadic immigrants with substantially more western Eurasian mitochondrial DNA lineages.

    PubMed

    Bogácsi-Szabó, Erika; Kalmár, Tibor; Csányi, Bernadett; Tömöry, Gyöngyvér; Czibula, Agnes; Priskin, Katalin; Horváth, Ferenc; Downes, Christopher Stephen; Raskó, István

    2005-10-01

    The Cumanians were originally Asian pastoral nomads who in the 13th century migrated to Hungary. We have examined mitochondrial DNA from members of the earliest Cumanian population in Hungary from two archeologically well-documented excavations and from 74 modern Hungarians from different rural locations in Hungary. Haplogroups were defined based on HVS I sequences and examinations of haplogroup-associated polymorphic sites of the protein coding region and of HVS II. To exclude contamination, some ancient DNA samples were cloned. A database was created from previously published mtDNA HVS I sequences (representing 2,615 individuals from different Asian and European populations) and 74 modem Hungarian sequences from the present study. This database was used to determine the relationships between the ancient Cumanians, modern Hungarians, and Eurasian populations and to estimate the genetic distances between these populations. We attempted to deduce the genetic trace of the migration of Cumanians. This study is the first ancient DNA characterization of an eastern pastoral nomad population that migrated into Europe. The results indicate that, while still possessing a Central Asian steppe culture, the Cumanians received a large admixture of maternal genes from more westerly populations before arriving in Hungary. A similar dilution of genetic, but not cultural, factors may have accompanied the settlement of other Asian nomads in Europe. PMID:16596944

  19. Mitochondrial haplogroups and hypervariable region polymorphisms in schizophrenia: a case-control study.

    PubMed

    Wang, Guo-xia; Zhang, Yong; Zhang, Yun-tao; Dong, Yu-shu; Lv, Zhuang-wei; Sun, Mao; Wu, Dan; Wu, Yuan-ming

    2013-10-30

    Previous studies have detected associations between mitochondrial haplogroups and schizophrenia (SZ). However, no study has examined the relationship between major mitochondrial DNA (mtDNA) haplogroups and SZ in the Chinese population. The aim of this study was to assess the association between mtDNA haplogroups and SZ genesis in the Chinese Han population. We used a case-control study and sequenced the mtDNA hypervariable regions (HVR1, HVR2, and HVR3) in the Han population. We analyzed mtDNA haplogroups and HVR polymorphisms in 298 SZ patients and 298 controls. The haplotypes were classified into 10 major haplogroups: A, B, CZ, D, F, G, M, N, N9a, and R. Statistical analysis revealed that only N9a showed a nominally significant association with protection from SZ [1.68% vs. 6.38%, p=0.004, OR=0.251 (0.092-0.680); after adjustment for age and sex: p=0.006, OR=0.246 (0.090-0.669)]. Three HVR polymorphisms were found to be nominally significantly different between subjects with SZ and controls, and all except one (m.204T>C) are linked to the N9a haplogroup. Our results indicate that mtDNA haplogroup N9a might be a protective factor for SZ. PMID:23374981

  20. Ashkenazi Jewish Centenarians Do Not Demonstrate Enrichment in Mitochondrial Haplogroup J

    PubMed Central

    Shlush, Liran I.; Atzmon, Gil; Weisshof, Roni; Behar, Doron; Yudkovsky, Guenady; Barzilai, Nir; Skorecki, Karl

    2008-01-01

    Background Association of mitochondrial haplogroup J with longevity has been reported in several population subgroups. While studies from northern Italy and Finland, have described a higher frequency of haplogroup J among centenarians in comparison to non-centenarian, several other studies could not replicate these results and suggested various explanations for the discrepancy. Methodology/Principal Findings We have evaluated haplogroup frequencies among Ashkenazi Jewish centenarians using two different sets of matched controls. No difference was observed in the haplogroup J frequencies between the centenarians or either matched control group, despite adequate statistical power to detect such a difference. Furthermore, the lack of association was robust to population substructure in the Ashkenazi Jewish population. Given this discrepancy with the previous reported associations in the northern Italian and the Finnish populations, we conducted re-analysis of these previously published data, which supported one of several possible explanations: i) inadequate matching of cases and controls; ii) inadequate adjustment for multiple comparison testing; iii) cryptic population stratification. Conclusions/Significance There does not exist a universal association of mitochondrial haplogroup J with longevity across all population groups. Reported associations in specialized populations may reflect genetic or other interactions specific to those populations or else cryptic confounding influences, such as inadequate matching attributable to population substructure, which are of general relevance to all studies of the possible association of mitochondrial DNA haplogroups with common complex phenotypes. PMID:18923645

  1. Mitochondrial Haplogroup X is Associated with Successful Aging in the Amish

    PubMed Central

    Courtenay, Monique D.; Gilbert, John R.; Jiang, Lan; Cummings, Anna C.; Gallins, Paul J.; Caywood, Laura; Reinhart-Mercer, Lori; Fuzzell, Denise; Knebusch, Claire; Laux, Renee; McCauley, Jacob L.; Jackson, Charles E.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Scott, William K.

    2016-01-01

    Avoiding disease, maintaining physical and cognitive function, and continued social engagement in long-lived individuals describe successful aging (SA). Mitochondrial lineages described by patterns of common genetic variants (“haplogroups”) have been associated with increased longevity in different populations. We investigated the influence of mitochondrial haplogroups on SA in an Amish community sample. Cognitively intact volunteers aged ≥80 (n=261) were enrolled in a door-to-door survey of Amish communities in Indiana and Ohio. Individuals scoring in the top third for lower extremity function, needing little assistance with self-care tasks, having no depression symptoms, and expressing high life satisfaction were considered SA (n=74). The remainder (n=187) were retained as controls. These individuals descend from 51 matrilines in a single 13 generation pedigree. Mitochondrial haplogroups were assigned using the 10 mitochondrial single nucleotide polymorphisms (mtSNPs) defining the nine most common European haplogroups. An additional 17 mtSNPs from a genome-wide association panel were also investigated. Associations between haplogroups, mtSNPs, and SA were determined by logistic regression models accounting for sex, age, body mass index, and matriline via generalized estimating equations. SA cases were more likely to carry Haplogroup X (OR=7.56, p=0.0015), and less likely to carry Haplogroup J (OR=0.40, p=0.0003). Our results represent a novel association of Haplogroup X with SA and suggest that variants in the mitochondrial genome may promote maintenance of both physical and cognitive function in older adults. PMID:21750925

  2. Origin and Post-Glacial Dispersal of Mitochondrial DNA Haplogroups C and D in Northern Asia

    PubMed Central

    Derenko, Miroslava; Malyarchuk, Boris; Grzybowski, Tomasz; Denisova, Galina; Rogalla, Urszula; Perkova, Maria; Dambueva, Irina; Zakharov, Ilia

    2010-01-01

    More than a half of the northern Asian pool of human mitochondrial DNA (mtDNA) is fragmented into a number of subclades of haplogroups C and D, two of the most frequent haplogroups throughout northern, eastern, central Asia and America. While there has been considerable recent progress in studying mitochondrial variation in eastern Asia and America at the complete genome resolution, little comparable data is available for regions such as southern Siberia – the area where most of northern Asian haplogroups, including C and D, likely diversified. This gap in our knowledge causes a serious barrier for progress in understanding the demographic pre-history of northern Eurasia in general. Here we describe the phylogeography of haplogroups C and D in the populations of northern and eastern Asia. We have analyzed 770 samples from haplogroups C and D (174 and 596, respectively) at high resolution, including 182 novel complete mtDNA sequences representing haplogroups C and D (83 and 99, respectively). The present-day variation of haplogroups C and D suggests that these mtDNA clades expanded before the Last Glacial Maximum (LGM), with their oldest lineages being present in the eastern Asia. Unlike in eastern Asia, most of the northern Asian variants of haplogroups C and D began the expansion after the LGM, thus pointing to post-glacial re-colonization of northern Asia. Our results show that both haplogroups were involved in migrations, from eastern Asia and southern Siberia to eastern and northeastern Europe, likely during the middle Holocene. PMID:21203537

  3. Relationship between mitochondrial haplogroup and physiological responses to hypobaric hypoxia.

    PubMed

    Motoi, Midori; Nishimura, Takayuki; Egashira, Yuka; Kishida, Fumi; Watanuki, Shigeki

    2016-01-01

    We aimed to investigate the relationship between mtDNA polymorphism and physiological responses to hypobaric hypoxia. The study included 28 healthy male students, consisting of 18 students in haplogroup D and 10 in haplogroup M7+G. Measurement sensors were attached to the participants for approximately 30 min in an environment with a temperature of 28 °C. After resting for 15 min, the programmed operation of the hypobaric chamber decreased the atmospheric pressure by 11.9 Torr every minute to simulate an increase in altitude of 150 m until 9.7 Torr (equivalent to 2500 m) and then decreased 9.7 Torr every minute until 465 Torr (equivalent to 4000 m). At each altitude, the pressure was maintained for 15 min and various measurements were taken. Haplogroup D showed higher SpO2 (p < 0.05) and significantly higher SpO2 during the pressure recovery period when compared with haplogroup M7+G. The distal skin temperature was higher in haplogroup D when compared with M7+G. These results suggested that haplogroup D maintained SpO2 at a higher level with higher peripheral blood flow during acute hypobaric exposure. PMID:27130215

  4. Large-Scale Mitochondrial DNA Analysis of the Domestic Goat Reveals Six Haplogroups with High Diversity

    PubMed Central

    Naderi, Saeid; Rezaei, Hamid-Reza; Taberlet, Pierre; Zundel, Stéphanie; Rafat, Seyed-Abbas; Naghash, Hamid-Reza; El-Barody, Mohamed A. A.; Ertugrul, Okan; Pompanon, François

    2007-01-01

    Background From the beginning of domestication, the transportation of domestic animals resulted in genetic and demographic processes that explain their present distribution and genetic structure. Thus studying the present genetic diversity helps to better understand the history of domestic species. Methodology/Principal Findings The genetic diversity of domestic goats has been characterized with 2430 individuals from all over the old world, including 946 new individuals from regions poorly studied until now (mainly the Fertile Crescent). These individuals represented 1540 haplotypes for the HVI segment of the mitochondrial DNA (mtDNA) control region. This large-scale study allowed the establishment of a clear nomenclature of the goat maternal haplogroups. Only five of the six previously defined groups of haplotypes were divergent enough to be considered as different haplogroups. Moreover a new mitochondrial group has been localized around the Fertile Crescent. All groups showed very high haplotype diversity. Most of this diversity was distributed among groups and within geographic regions. The weak geographic structure may result from the worldwide distribution of the dominant A haplogroup (more than 90% of the individuals). The large-scale distribution of other haplogroups (except one), may be related to human migration. The recent fragmentation of local goat populations into discrete breeds is not detectable with mitochondrial markers. The estimation of demographic parameters from mismatch analyses showed that all groups had a recent demographic expansion corresponding roughly to the period when domestication took place. But even with a large data set it remains difficult to give relative dates of expansion for different haplogroups because of large confidence intervals. Conclusions/Significance We propose standard criteria for the definition of the different haplogroups based on the result of mismatch analysis and on the use of sequences of reference. Such a

  5. Mitochondrial DNA Haplogroups influence lipoatrophy after Highly Active Anti-retroviral Therapy

    PubMed Central

    Hendrickson, Sher L.; Kingsley, Lawrence A.; Ruiz-Pesini, Eduardo; Poole, Jason C.; Jacobson, Lisa P.; Palella, Frank J.; Bream, Jay H.; Wallace, Douglas C.; O’Brien, Stephen J.

    2009-01-01

    Although highly active retroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggests that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV-infected European American patients on HAART in the Multicenter AIDS cohort Study (MACS) and found that mitochondrial haplogroup H was strongly associated with increased atrophy (arms: p = 0.007, OR = 1.77, 95% CI = 1.17–2.69 legs: p = 0.037, OR = 1.54 95% CI = 1.03–2.31, and buttocks: p = 0.10, OR = 1.41 95% CI = 0.94–2.12). We also saw borderline significance for haplogroup T as protective against lipoatrophy (p = 0.05, OR = 0.52, 95% CI = 0.20–1.00). These data suggest that mitochondrial DNA haplogroup may influence the propensity for lipoatrophy in patients receiving NRTIs. PMID:19339895

  6. Mitochondrial haplogroups and control region polymorphisms in Kaposi's sarcoma patients.

    PubMed

    Jalilvand, Somayeh; Shoja, Zabihollah; Marashi, Sayed Mahdi; Shahmahmoodi, Shohreh; Safaie-Naraghi, Zahra; Nourijelyani, Keramat; Nesheli, Asgar Baghernejad; Mokhtari-Azad, Talat

    2015-09-01

    Inflammation and reactive oxygen species (ROS) production have recently considered as key mechanisms in the pathogenesis of Kaposi's sarcoma (KS). Since mitochondria are the major source of ROS production, this organelle may play a main role in KS development. However, there are no studies on mtDNA variations and haplogroups in this area. The focus of this study was to investigate the mtDNA variants and haplogroups in KS patients and their relationship to tumor development. To address this, we have genotyped mtDNA in 45 Iranian KS patients and 48 age and sex-matched Iranian controls. A strong positive correlation was observed between UK cluster and decreased risk of KS. Our results suggest that the UK cluster might be a protective haplogroup for KS development. It is probably superhaplogroup UK, with lower ATP and ROS production, may prevent KSHV reactivation from latent to lytic phase that is essential for KS development. PMID:25879916

  7. The complete mitochondrial genome of Eurasian water shrew (Neomys fodiens).

    PubMed

    Liu, Zhitao; Zhao, Wenge; Liu, Peng; Li, Shulan; Xu, Chunzhu

    2016-07-01

    The complete mitogenome sequence of Eurasian water shrew (Neomys fodiens) was determined using long PCR. The genome was 17,260 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region. The overall base composition of the heavy strand is A (33.0%), C (23.2%), T (30.9%) and G (12.9%). The base compositions present clearly the A-T skew, which is most obviously in the control region and protein-coding genes. The extended termination-associated sequence domain, the central conserved domain and the conserved sequence block domain are defined in the mitochondrial genome control region of Eurasian water shrew. Mitochondrial genomes analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. Neomys elegans, Soriculus fumidus, and N. fodiens formed a monophyletic group with the high bootstrap value (100%) in all examinations. This clade with the Anourosorex squamipes as the sister taxon to Sorex. PMID:26006281

  8. Generation of a human control iPSC line with a European mitochondrial haplogroup U background.

    PubMed

    Galera, Teresa; Zurita, Francisco; González-Páramos, Cristina; Moreno-Izquierdo, Ana; Fraga, Mario F; Fernández, Agustin F; Garesse, Rafael; Gallardo, M Esther

    2016-01-01

    Human iPSC line N44SV.5 was generated from primary normal human dermal fibroblasts belonging to the European mitochondrial haplogroup U. For this purpose, reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus. PMID:27345790

  9. Relationship between European Mitochondrial Haplogroups and Chronic Renal Allograft Rejection in Patients with Kidney Transplant

    PubMed Central

    JIMÉNEZ-SOUSA, María Angeles; TAMAYO, Eduardo; GUZMÁN-FULGENCIO, María; FERNÁNDEZ-RODRÍGUEZ, Amanda; HEREDIA-RODRIGUEZ, María; GARCÍA-ÁLVAREZ, Mónica; BERMEJO-MARTIN, Jesús F; PINEDA-TENOR, Daniel; RUIZ-GRANADO, Patricia; ALVAREZ-FUENTE, Elisa; GÓMEZ-SANCHEZ, Esther; GÓMEZ-HERRERAS, José I; RESINO, Salvador

    2014-01-01

    Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom's MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction. PMID:25170295

  10. Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment

    PubMed Central

    2014-01-01

    Background Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995–2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant’s address. Results Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects. PMID:24884505

  11. A mitochondrial haplogroup is associated with decreased longevity in a historic new world population.

    PubMed

    Castri, Loredana; Luiselli, Donata; Pettener, Davide; Melendez-Obando, Mauricio; Villegas-Palma, Ramón; Barrantes, Ramiro; Madrigal, Lorena

    2014-01-01

    Interest in mitochondrial influences on extended longevity has been mounting, as evidenced by a growing literature. Such work has demonstrated that some haplogroups are associated with increased longevity and that such associations are population specific. Most previous work, however, suffers from the methodological shortcoming that long-lived individuals are compared with "controls" who are born decades after the aged individuals. The only true controls of the elderly are people who were born in the same time period but who did not have extended longevity. Here we present results of a study in which we are able to test whether longevity is independent of haplogroup type, controlling for time period, by using mtDNA genealogies. Since mtDNA does not recombine, we know the mtDNA haplogroup of the maternal ancestors of our living participants. Thus, we can compare the haplogroup of people with and without extended longevity who were born during the same time period. Our sample is an admixed New World population that has haplogroups of Amerindian, European, and African origin. We show that women who belong to Amerindian, European, and African haplogroups do not differ in their mean longevity. Therefore, to the extent that ethnicity was tied in this population to mtDNA make-up, such ethnicity did not impact longevity. In support of previous suggestions that the link between mtDNA haplogroups and longevity is specific to the population being studied, we found an association between haplogroup C and decreased longevity. Interestingly, the lifetime reproductive success and the number of grandchildren produced via a daughter of women with haplogroup C are not reduced. Our diachronic approach to the mtDNA and longevity link allowed us to determine that the same haplogroup is associated with decreased longevity during different time periods and allowed us to compare the haplogroup of short- and long-lived individuals born during the same time period. By controlling for time

  12. Sisters' curse: sexually antagonistic effects constrain the spread of a mitochondrial haplogroup superior in sperm competition.

    PubMed

    Padua, Michael V; Zeh, David W; Bonilla, Melvin M; Zeh, Jeanne A

    2014-12-22

    Maternal inheritance of mitochondria creates a sex-specific selective sieve with implications for male longevity, disease susceptibility and infertility. Because males are an evolutionary dead end for mitochondria, mitochondrial mutations that are harmful or beneficial to males but not females cannot respond directly to selection. Although the importance of this male/female asymmetry in evolutionary response depends on the extent to which mitochondrial mutations exert antagonistic effects on male and female fitness, few studies have documented sex-specific selection acting on mitochondria. Here, we exploited the discovery of two highly divergent mitochondrial haplogroups (A and B2) in central Panamanian populations of the pseudoscorpion Cordylochernes scorpioides. Next-generation sequencing and phylogenetic analyses suggest that selection on the ND4 and ND4L mitochondrial genes may partially explain sexually antagonistic mitochondrial effects on reproduction. Males carrying the rare B2 mitochondrial haplogroup enjoy a marked advantage in sperm competition, but B2 females are significantly less sexually receptive at second mating than A females. This reduced propensity for polyandry is likely to significantly reduce female lifetime reproductive success, thereby limiting the spread of the male beneficial B2 haplogroup. Our findings suggest that maternal inheritance of mitochondria and sexually antagonistic selection can constrain male adaptation and sexual selection in nature. PMID:25377452

  13. Mitochondrial DNA haplogroups and susceptibility to prostate cancer in a colombian population.

    PubMed

    Cano, D; Gomez, C F; Ospina, N; Cajigas, J A; Groot, H; Andrade, R E; Torres, M M

    2014-01-01

    Prostate cancer (PC) is one of the most common cancers and the second leading cause of mortality from cancer in Colombian men. Mitochondrial DNA (mtDNA) haplogroups have been associated with the risk of PC. Several studies have demonstrated dramatic differences regarding the risk of PC among men from different ethnic backgrounds. The present study was aimed at assessing the relationship between mtDNA haplogroups and PC. The mitochondrial DNA hypervariable segment I (HSV-1) was sequenced in a population-based study covering 168 cases (CA) and 140 unrelated healthy individuals as a control group (CG). A total of 92 different mtDNA sequences were found in CA and 59 were found in the CG. According to the geographical origin attributed to each mtDNA haplogroup, 82% of the mtDNA sequences found in both groups were Native Americans (A, B, C, and D). The most frequent was A (41.1%CA-42.1%CG), followed by B (22.0%CA-21.4%CG), C (12.0%CA-11.4%CG), and D (6%CA-10.0%CG). A lower percentage of European haplogroups (U, H, K, J, M, T, and HV) were also found (13.1%CA-12.9%CG), likewise African haplogroups (L0, L1, L2, and L3) (6.5%CA-2.1%CG). There were no statistically significant differences between the distribution of mtDNA haplogroups in CA and the CG in this study. PMID:24616820

  14. Mitochondrial DNA Haplogroups and Susceptibility to Prostate Cancer in a Colombian Population

    PubMed Central

    Cano, D.; Gomez, C. F.; Ospina, N.; Cajigas, J. A.; Groot, H.; Andrade, R. E.; Torres, M. M.

    2014-01-01

    Prostate cancer (PC) is one of the most common cancers and the second leading cause of mortality from cancer in Colombian men. Mitochondrial DNA (mtDNA) haplogroups have been associated with the risk of PC. Several studies have demonstrated dramatic differences regarding the risk of PC among men from different ethnic backgrounds. The present study was aimed at assessing the relationship between mtDNA haplogroups and PC. The mitochondrial DNA hypervariable segment I (HSV-1) was sequenced in a population-based study covering 168 cases (CA) and 140 unrelated healthy individuals as a control group (CG). A total of 92 different mtDNA sequences were found in CA and 59 were found in the CG. According to the geographical origin attributed to each mtDNA haplogroup, 82% of the mtDNA sequences found in both groups were Native Americans (A, B, C, and D). The most frequent was A (41.1%CA–42.1%CG), followed by B (22.0%CA–21.4%CG), C (12.0%CA–11.4%CG), and D (6%CA–10.0%CG). A lower percentage of European haplogroups (U, H, K, J, M, T, and HV) were also found (13.1%CA–12.9%CG), likewise African haplogroups (L0, L1, L2, and L3) (6.5%CA–2.1%CG). There were no statistically significant differences between the distribution of mtDNA haplogroups in CA and the CG in this study. PMID:24616820

  15. Fine Dissection of Human Mitochondrial DNA Haplogroup HV Lineages Reveals Paleolithic Signatures from European Glacial Refugia

    PubMed Central

    Sarno, Stefania; Sevini, Federica; Vianello, Dario; Tamm, Erika; Metspalu, Ene; van Oven, Mannis; Hübner, Alexander; Sazzini, Marco; Franceschi, Claudio; Pettener, Davide; Luiselli, Donata

    2015-01-01

    Genetic signatures from the Paleolithic inhabitants of Eurasia can be traced from the early divergent mitochondrial DNA lineages still present in contemporary human populations. Previous studies already suggested a pre-Neolithic diffusion of mitochondrial haplogroup HV*(xH,V) lineages, a relatively rare class of mtDNA types that includes parallel branches mainly distributed across Europe and West Asia with a certain degree of structure. Up till now, variation within haplogroup HV was addressed mainly by analyzing sequence data from the mtDNA control region, except for specific sub-branches, such as HV4 or the widely distributed haplogroups H and V. In this study, we present a revised HV topology based on full mtDNA genome data, and we include a comprehensive dataset consisting of 316 complete mtDNA sequences including 60 new samples from the Italian peninsula, a previously underrepresented geographic area. We highlight points of instability in the particular topology of this haplogroup, reconstructed with BEAST-generated trees and networks. We also confirm a major lineage expansion that probably followed the Late Glacial Maximum and preceded Neolithic population movements. We finally observe that Italy harbors a reservoir of mtDNA diversity, with deep-rooting HV lineages often related to sequences present in the Caucasus and the Middle East. The resulting hypothesis of a glacial refugium in Southern Italy has implications for the understanding of late Paleolithic population movements and is discussed within the archaeological cultural shifts occurred over the entire continent. PMID:26640946

  16. Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults

    PubMed Central

    Ebner, Sabine; Mangge, Harald; Langhof, Helmut; Halle, Martin; Siegrist, Monika; Aigner, Elmar; Paulmichl, Katharina; Paulweber, Bernhard; Datz, Christian; Sperl, Wolfgang; Kofler, Barbara; Weghuber, Daniel

    2015-01-01

    Background Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians. Methodology and Principal Findings Using SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2–2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects. Conclusions and Significance By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor. PMID:26322975

  17. Origin and Spread of Bos taurus: New Clues from Mitochondrial Genomes Belonging to Haplogroup T1

    PubMed Central

    Bonfiglio, Silvia; Ginja, Catarina; De Gaetano, Anna; Achilli, Alessandro; Olivieri, Anna; Colli, Licia; Tesfaye, Kassahun; Agha, Saif Hassan; Gama, Luis T.; Cattonaro, Federica; Penedo, M. Cecilia T; Ajmone-Marsan, Paolo; Torroni, Antonio; Ferretti, Luca

    2012-01-01

    Background Most genetic studies on modern cattle have established a common origin for all taurine breeds in the Near East, during the Neolithic transition about 10 thousand years (ka) ago. Yet, the possibility of independent and/or secondary domestication events is still debated and is fostered by the finding of rare mitochondrial DNA (mtDNA) haplogroups like P, Q and R. Haplogroup T1, because of its geographic distribution, has been the subject of several investigations pointing to a possible independent domestication event in Africa and suggesting a genetic contribution of African cattle to the formation of Iberian and Creole cattle. Whole mitochondrial genome sequence analysis, with its proven effectiveness in improving the resolution of phylogeographic studies, is the most appropriate tool to investigate the origin and structure of haplogroup T1. Methodology A survey of >2200 bovine mtDNA control regions representing 28 breeds (15 European, 10 African, 3 American) identified 281 subjects belonging to haplogroup T1. Fifty-four were selected for whole mtDNA genome sequencing, and combined with ten T1 complete sequences from previous studies into the most detailed T1 phylogenetic tree available to date. Conclusions Phylogenetic analysis of the 64 T1 mitochondrial complete genomes revealed six distinct sub-haplogroups (T1a–T1f). Our data support the overall scenario of a Near Eastern origin of the T1 sub-haplogroups from as much as eight founding T1 haplotypes. However, the possibility that one sub-haplogroup (T1d) arose in North Africa, in domesticated stocks, shortly after their arrival from the Near East, can not be ruled out. Finally, the previously identified “African-derived American" (AA) haplotype turned out to be a sub-clade of T1c (T1c1a1). This haplotype was found here for the first time in Africa (Egypt), indicating that it probably originated in North Africa, reached the Iberian Peninsula and sailed to America, with the first European settlers

  18. Association of mitochondrial DNA haplogroups and vascular complications of diabetes mellitus: A population-based study.

    PubMed

    Martikainen, Mika H; Rönnemaa, Tapani; Majamaa, Kari

    2015-07-01

    We investigated whether mitochondrial (mtDNA) haplogroups and maternal family history of diabetes mellitus were associated with vascular diabetes mellitus complications in a population-based cohort of 299 Finnish diabetes mellitus patients with disease onset in young adult age. We found that haplogroup U was more prevalent among patients with no vascular diabetes mellitus complications than among those with at least one complication (p = 0.038). Haplogroup U was also more prevalent among the patients who reported maternal family history of diabetes mellitus than among those who did not (p = 0.0013). Furthermore, haplogroup U was more prevalent among patients with maternal family history of diabetes mellitus but no vascular diabetes mellitus complications than among those with at least one vascular diabetes mellitus complication but no maternal family history of diabetes mellitus (p = 0.0003 for difference). These findings suggest that different mtDNA-related factors may influence the risk of diabetes mellitus per se and the risk of vascular diabetes mellitus complications. Further studies are, however, warranted to replicate and elaborate on these results. PMID:25920916

  19. Association of primary open-angle glaucoma with mitochondrial variants and haplogroups common in African Americans

    PubMed Central

    Gudiseva, Harini V.; Trachtman, Benjamin; Bowman, Anita S.; Sagaser, Anna; Sankar, Prithvi; Miller-Ellis, Eydie; Lehman, Amanda; Addis, Victoria; O'Brien, Joan M.

    2016-01-01

    Purpose To estimate the population frequencies of all common mitochondrial variants and ancestral haplogroups among 1,999 subjects recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study, including 1,217 primary open-angle glaucoma (POAG) cases and 782 controls, and to identify ancestral subpopulations and mitochondrial mutations as potential risk factors for POAG susceptibility. Methods Subject classification by characteristic glaucomatous optic nerve findings and corresponding visual field defects, as defined by enrolling glaucoma specialists, stereo disc photography, phlebotomy, extraction of total DNA from peripheral blood or saliva, DNA quantification and normalization, PCR amplification of whole mitochondrial genomes, Ion Torrent deep semiconductor DNA sequencing on DNA pools (“Pool-seq”), Sanger sequencing of 3,479 individual mitochondrial DNAs, and bioinformatic analysis. Results The distribution of common African haplogroups within the POAAGG study population was broadly similar to prior surveys of African Americans. However, the POAG case population was found to be enriched in L1c2 haplogroups, which are defined in part by missense mutations m.6150G>A (Val83Ile, odds ratio [OR] 1.8, p=0.01), m.6253C>T (Met117Thr, rs200165736, OR 1.6, p=0.04), and m.6480G>A (Val193Ile, rs199476128, OR 4.6, p=0.04) in the cytochrome c oxidase subunit 1 (MT-CO1) gene and by a variant, m.2220A>G (OR 2.0, p=0.01), in MT-RNR2, which encodes the mitochondrial ribosomal 16s RNA gene. L2 haplogroups were predicted to be overrepresented in the POAG case population by Pool-seq, and the difference was confirmed to be significant with Sanger sequencing, that targeted the L2-associated variants m.2416T>C (rs28358580, OR 1.2, p=0.02) and m.2332C>T (OR 1.2, p=.02) in MT-RNR2. Another variant within MT-RNR2, m.3010G>A (rs3928306), previously implicated in sensitivity to the optic neuropathy-associated antibiotic linezolid, and arising on D4 and J1

  20. Mitochondrial DNA Haplogroup A may confer a genetic susceptibility to AIDS group from Southwest China.

    PubMed

    Wang, Hua-Wei; Xu, Yu; Miao, Ying-Lei; Luo, Hua-You; Wang, Kun-Hua

    2016-05-01

    The acquired immunodeficiency syndrome (AIDS) in humans was one of the chronic infections caused by human immunodeficiency virus (HIV), and the interactions between viral infection and mitochondrial energetic implicated that mitochondrial DNA (mtDNA) variation(s) may effect genetic susceptibility to AIDS. Thus, to illustrate the maternal genetic structure and further identify whether mtDNA variation(s) can effect HIV infection among southwest Chinese AIDS group, the whole mtDNA control region sequences of 70 AIDS patients and 480 health individuals from southwest China were analyzed here. Our results indicated the plausible recent genetic admixture results of AIDS group; comparison of matrilineal components between AIDS and matched Han groups showed that mtDNA haplogroup A (p = 0.048, OR = 3.006, 95% CI = 1.109-8.145) has a significant higher difference between the two groups; further comparison illustrated that mtDNA mutations 16,209 (p = 0.046, OR = 2.607, 95% CI = 0.988-6.876) and 16,319 (p = 0.009, OR = 2.965, 95% CI = 1.278-6.876) have significant differences between AIDS and matched control groups, and both of which were the defining variations of mtDNA haplogroup A, they further confirmed that mtDNA haplogroup A may confer genetic susceptibility to AIDS. Our results suggested that haplogroup A may confer a genetic susceptibility to AIDS group from Southwest China. PMID:25431816

  1. Multiplex APLP System for High-Resolution Haplogrouping of Extremely Degraded East-Asian Mitochondrial DNAs.

    PubMed

    Kakuda, Tsuneo; Shojo, Hideki; Tanaka, Mayumi; Nambiar, Phrabhakaran; Minaguchi, Kiyoshi; Umetsu, Kazuo; Adachi, Noboru

    2016-01-01

    Mitochondrial DNA (mtDNA) serves as a powerful tool for exploring matrilineal phylogeographic ancestry, as well as for analyzing highly degraded samples, because of its polymorphic nature and high copy numbers per cell. The recent advent of complete mitochondrial genome sequencing has led to improved techniques for phylogenetic analyses based on mtDNA, and many multiplex genotyping methods have been developed for the hierarchical analysis of phylogenetically important mutations. However, few high-resolution multiplex genotyping systems for analyzing East-Asian mtDNA can be applied to extremely degraded samples. Here, we present a multiplex system for analyzing mitochondrial single nucleotide polymorphisms (mtSNPs), which relies on a novel amplified product-length polymorphisms (APLP) method that uses inosine-flapped primers and is specifically designed for the detailed haplogrouping of extremely degraded East-Asian mtDNAs. We used fourteen 6-plex polymerase chain reactions (PCRs) and subsequent electrophoresis to examine 81 haplogroup-defining SNPs and 3 insertion/deletion sites, and we were able to securely assign the studied mtDNAs to relevant haplogroups. Our system requires only 1×10-13 g (100 fg) of crude DNA to obtain a full profile. Owing to its small amplicon size (<110 bp), this new APLP system was successfully applied to extremely degraded samples for which direct sequencing of hypervariable segments using mini-primer sets was unsuccessful, and proved to be more robust than conventional APLP analysis. Thus, our new APLP system is effective for retrieving reliable data from extremely degraded East-Asian mtDNAs. PMID:27355212

  2. Multiplex APLP System for High-Resolution Haplogrouping of Extremely Degraded East-Asian Mitochondrial DNAs

    PubMed Central

    Kakuda, Tsuneo; Shojo, Hideki; Tanaka, Mayumi; Nambiar, Phrabhakaran; Minaguchi, Kiyoshi; Umetsu, Kazuo; Adachi, Noboru

    2016-01-01

    Mitochondrial DNA (mtDNA) serves as a powerful tool for exploring matrilineal phylogeographic ancestry, as well as for analyzing highly degraded samples, because of its polymorphic nature and high copy numbers per cell. The recent advent of complete mitochondrial genome sequencing has led to improved techniques for phylogenetic analyses based on mtDNA, and many multiplex genotyping methods have been developed for the hierarchical analysis of phylogenetically important mutations. However, few high-resolution multiplex genotyping systems for analyzing East-Asian mtDNA can be applied to extremely degraded samples. Here, we present a multiplex system for analyzing mitochondrial single nucleotide polymorphisms (mtSNPs), which relies on a novel amplified product-length polymorphisms (APLP) method that uses inosine-flapped primers and is specifically designed for the detailed haplogrouping of extremely degraded East-Asian mtDNAs. We used fourteen 6-plex polymerase chain reactions (PCRs) and subsequent electrophoresis to examine 81 haplogroup-defining SNPs and 3 insertion/deletion sites, and we were able to securely assign the studied mtDNAs to relevant haplogroups. Our system requires only 1×10−13 g (100 fg) of crude DNA to obtain a full profile. Owing to its small amplicon size (<110 bp), this new APLP system was successfully applied to extremely degraded samples for which direct sequencing of hypervariable segments using mini-primer sets was unsuccessful, and proved to be more robust than conventional APLP analysis. Thus, our new APLP system is effective for retrieving reliable data from extremely degraded East-Asian mtDNAs. PMID:27355212

  3. HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing

    PubMed Central

    Weissensteiner, Hansi; Pacher, Dominic; Kloss-Brandstätter, Anita; Forer, Lukas; Specht, Günther; Bandelt, Hans-Jürgen; Kronenberg, Florian; Salas, Antonio; Schönherr, Sebastian

    2016-01-01

    Mitochondrial DNA (mtDNA) profiles can be classified into phylogenetic clusters (haplogroups), which is of great relevance for evolutionary, forensic and medical genetics. With the extensive growth of the underlying phylogenetic tree summarizing the published mtDNA sequences, the manual process of haplogroup classification would be too time-consuming. The previously published classification tool HaploGrep provided an automatic way to address this issue. Here, we present the completely updated version HaploGrep 2 offering several advanced features, including a generic rule-based system for immediate quality control (QC). This allows detecting artificial recombinants and missing variants as well as annotating rare and phantom mutations. Furthermore, the handling of high-throughput data in form of VCF files is now directly supported. For data output, several graphical reports are generated in real time, such as a multiple sequence alignment format, a VCF format and extended haplogroup QC reports, all viewable directly within the application. In addition, HaploGrep 2 generates a publication-ready phylogenetic tree of all input samples encoded relative to the revised Cambridge Reference Sequence. Finally, new distance measures and optimizations of the algorithm increase accuracy and speed-up the application. HaploGrep 2 can be accessed freely and without any registration at http://haplogrep.uibk.ac.at. PMID:27084951

  4. HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing.

    PubMed

    Weissensteiner, Hansi; Pacher, Dominic; Kloss-Brandstätter, Anita; Forer, Lukas; Specht, Günther; Bandelt, Hans-Jürgen; Kronenberg, Florian; Salas, Antonio; Schönherr, Sebastian

    2016-07-01

    Mitochondrial DNA (mtDNA) profiles can be classified into phylogenetic clusters (haplogroups), which is of great relevance for evolutionary, forensic and medical genetics. With the extensive growth of the underlying phylogenetic tree summarizing the published mtDNA sequences, the manual process of haplogroup classification would be too time-consuming. The previously published classification tool HaploGrep provided an automatic way to address this issue. Here, we present the completely updated version HaploGrep 2 offering several advanced features, including a generic rule-based system for immediate quality control (QC). This allows detecting artificial recombinants and missing variants as well as annotating rare and phantom mutations. Furthermore, the handling of high-throughput data in form of VCF files is now directly supported. For data output, several graphical reports are generated in real time, such as a multiple sequence alignment format, a VCF format and extended haplogroup QC reports, all viewable directly within the application. In addition, HaploGrep 2 generates a publication-ready phylogenetic tree of all input samples encoded relative to the revised Cambridge Reference Sequence. Finally, new distance measures and optimizations of the algorithm increase accuracy and speed-up the application. HaploGrep 2 can be accessed freely and without any registration at http://haplogrep.uibk.ac.at. PMID:27084951

  5. Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010 controls

    PubMed Central

    Chinnery, P F; Mowbray, C; Patel, S K; Elson, J L; Sampson, M; Hitman, G A; McCarthy, M I; Hattersley, A T; Walker, M

    2007-01-01

    Mitochondria play a central role in the secretion of insulin by pancreatic β‐cells, and pathogenic mutations of mitochondrial DNA (mtDNA) can cause diabetes. The aetiology of type 2 diabetes has a strong genetic component, raising the possibility that genetic variants of mtDNA alter the risk of developing the disorder. Recent studies have produced conflicting results. By studying 897 UK cases of type 2 diabetes and 1010 population‐matched controls, it is shown that European mtDNA haplogroups are unlikely to play a major role in the risk of developing the disorder. PMID:17551080

  6. The Structure of Diversity within New World Mitochondrial DNA Haplogroups: Implications for the Prehistory of North America

    PubMed Central

    Malhi, Ripan S.; Eshleman, Jason A.; Greenberg, Jonathan A.; Weiss, Deborah A.; Shook, Beth A. Schultz; Kaestle, Frederika A.; Lorenz, Joseph G.; Kemp, Brian M.; Johnson, John R.; Smith, David Glenn

    2002-01-01

    The mitochondrial DNA haplogroups and hypervariable segment I (HVSI) sequences of 1,612 and 395 Native North Americans, respectively, were analyzed to identify major prehistoric population events in North America. Gene maps and spatial autocorrelation analyses suggest that populations with high frequencies of haplogroups A, B, and X experienced prehistoric population expansions in the North, Southwest, and Great Lakes region, respectively. Haplotype networks showing high levels of reticulation and high frequencies of nodal haplotypes support these results. The haplotype networks suggest the existence of additional founding lineages within haplogroups B and C; however, because of the hypervariability exhibited by the HVSI data set, similar haplotypes exhibited in Asia and America could be due to convergence rather than common ancestry. The hypervariability and reticulation preclude the use of estimates of genetic diversity within haplogroups to argue for the number of migrations to the Americas. PMID:11845406

  7. Mitochondrial DNA haplogroup phylogeny of the dog: Proposal for a cladistic nomenclature.

    PubMed

    Fregel, Rosa; Suárez, Nicolás M; Betancor, Eva; González, Ana M; Cabrera, Vicente M; Pestano, José

    2015-05-01

    Canis lupus familiaris mitochondrial DNA analysis has increased in recent years, not only for the purpose of deciphering dog domestication but also for forensic genetic studies or breed characterization. The resultant accumulation of data has increased the need for a normalized and phylogenetic-based nomenclature like those provided for human maternal lineages. Although a standardized classification has been proposed, haplotype names within clades have been assigned gradually without considering the evolutionary history of dog mtDNA. Moreover, this classification is based only on the D-loop region, proven to be insufficient for phylogenetic purposes due to its high number of recurrent mutations and the lack of relevant information present in the coding region. In this study, we design 1) a refined mtDNA cladistic nomenclature from a phylogenetic tree based on complete sequences, classifying dog maternal lineages into haplogroups defined by specific diagnostic mutations, and 2) a coding region SNP analysis that allows a more accurate classification into haplogroups when combined with D-loop sequencing, thus improving the phylogenetic information obtained in dog mitochondrial DNA studies. PMID:25869968

  8. The Peopling of Europe from the Mitochondrial Haplogroup U5 Perspective

    PubMed Central

    Malyarchuk, Boris; Derenko, Miroslava; Grzybowski, Tomasz; Perkova, Maria; Rogalla, Urszula; Vanecek, Tomas; Tsybovsky, Iosif

    2010-01-01

    It is generally accepted that the most ancient European mitochondrial haplogroup, U5, has evolved essentially in Europe. To resolve the phylogeny of this haplogroup, we completely sequenced 113 mitochondrial genomes (79 U5a and 34 U5b) of central and eastern Europeans (Czechs, Slovaks, Poles, Russians and Belorussians), and reconstructed a detailed phylogenetic tree, that incorporates previously published data. Molecular dating suggests that the coalescence time estimate for the U5 is ∼25–30 thousand years (ky), and ∼16–20 and ∼20–24 ky for its subhaplogroups U5a and U5b, respectively. Phylogeographic analysis reveals that expansions of U5 subclusters started earlier in central and southern Europe, than in eastern Europe. In addition, during the Last Glacial Maximum central Europe (probably, the Carpathian Basin) apparently represented the area of intermingling between human flows from refugial zones in the Balkans, the Mediterranean coastline and the Pyrenees. Age estimations amounting for many U5 subclusters in eastern Europeans to ∼15 ky ago and less are consistent with the view that during the Ice Age eastern Europe was an inhospitable place for modern humans. PMID:20422015

  9. Timing and deciphering mitochondrial DNA macro-haplogroup R0 variability in Central Europe and Middle East

    PubMed Central

    2008-01-01

    Background Nearly half of the West Eurasian assemblage of human mitochondrial DNA (mtDNA) is fractioned into numerous sub-lineages of the predominant haplogroup (hg) R0. Several hypotheses have been proposed on the origin and the expansion times of some R0 sub-lineages, which were partially inconsistent with each other. Here we describe the phylogenetic structure and genetic variety of hg R0 in five European populations and one population from the Middle East. Results Our analysis of 1,350 mtDNA haplotypes belonging to R0, including entire control region sequences and 45 single nucleotide polymorphisms from the coding region, revealed significant differences in the distribution of different sub-hgs even between geographically closely located regions. Estimates of coalescence times that were derived using diverse algorithmic approaches consistently affirmed that the major expansions of the different R0 hgs occurred in the terminal Pleistocene and early Holocene. Conclusion Given an estimated coalescence time of the distinct lineages of 10 – 18 kya, the differences in the distributions could hint to either limited maternal gene flow after the Last Glacial Maximum due to the alpine nature of the regions involved or to a stochastic loss of diversity due to environmental events and/or disease episodes occurred at different times and in distinctive regions. Our comparison of two different ways of obtaining the timing of the most recent common ancestor confirms that the time of a sudden expansion can be adequately recovered from control region data with valid confidence intervals. For reliable estimates, both procedures should be applied in order to cross-check the results for validity and soundness. PMID:18601722

  10. Altered mitochondrial dynamics and response to insulin in cybrid cells harboring a diabetes-susceptible mitochondrial DNA haplogroup.

    PubMed

    Kuo, Hsiao-Mei; Weng, Shao-Wen; Chang, Alice Y W; Huang, Hung-Tu; Lin, Hung-Yu; Chuang, Jiin-Haur; Lin, Tsu-Kung; Liou, Chia-Wei; Tai, Ming-Hong; Lin, Ching-Yi; Wang, Pei-Wen

    2016-07-01

    The advantage of using a cytoplasmic hybrid (cybrid) model to study the genetic effects of mitochondria is that the cells have the same nuclear genomic background. We previously demonstrated the independent role of mitochondria in the pathogenesis of insulin resistance (IR) and pro-inflammation in type 2 diabetes. In this study, we compared mitochondrial dynamics and related physiological functions between cybrid cells harboring diabetes-susceptible (B4) and diabetes-protective (D4) mitochondrial haplogroups, especially the responses before and after insulin stimulation. Cybrid B4 showed a more fragmented mitochondrial network, impaired mitochondrial biogenesis and bioenergetics, increased apoptosis and ineffective mitophagy and a low expression of fusion-related molecules. Upon insulin stimulation, increases in network formation, mitochondrial DNA (mtDNA) content, and ATP production were observed only in cybrid D4. Insulin promoted a pro-fusion dynamic status in both cybrids, but the trend was greater in cybrid D4. In cybrid B4, the imbalance of mitochondrial dynamics and impaired biogenesis and bioenergetics, and increased apoptosis were significantly improved in response to antioxidant treatment. We concluded that diabetes-susceptible mtDNA variants are themselves resistant to insulin. PMID:27107769

  11. Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: implications for population susceptibility to diseases.

    PubMed

    Kenney, M Cristina; Chwa, Marilyn; Atilano, Shari R; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Tarek, Mohamed; Del Carpio, Javier Cáceres; Nesburn, Anthony B; Boyer, David S; Kuppermann, Baruch D; Vawter, Marquis P; Jazwinski, S Michal; Miceli, Michael V; Wallace, Douglas C; Udar, Nitin

    2014-02-01

    The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 (chemokine, CC motif, receptor 3) signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases. PMID:24200652

  12. Molecular and Bioenergetic Differences between Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Implications for Population Susceptibility to Diseases

    PubMed Central

    Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Tarek, Mohamed; Cáceres del Carpio, Javier; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Vawter, Marquis P.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin

    2015-01-01

    The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP turnover rates and lower levels of ROS production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases. PMID:24200652

  13. The Mitochondrial DNA Northeast Asia CZD Haplogroup Is Associated with Good Disease-Free Survival among Male Oral Squamous Cell Carcinoma Patients

    PubMed Central

    Lai, Chih-Hsiung; Huang, Shiang-Fu; Chen, I-How; Liao, Chun-Ta; Wang, Hung-Ming; Hsieh, Ling-Ling

    2012-01-01

    Reprogramming of energy metabolism in cancer cells has been directly/indirectly linked to mitochondria and mitochondrial functional defects and these changes seem to contribute to the development and progression of cancer. Studies have indicated that mitochondrial DNA haplogroups are associated with risk in relation to various diseases including cancer. However, few studies have examined the effect of haplogroups on cancer prognosis outcome. In order to explore the role of haplogroups on oral squamous cell carcinoma (OSCC) prognosis, the mitochondrial genomes of 300 male OSCC patients were comprehensively analyzed by direct sequencing. They were then haplotyped and grouped into four major geographic haplogroups, namely the East Asia AN, Southeast Asia RBF, East Asia MGE and Northeast Asia CZD groups. The Kaplan-Meier plot analysis indicated that individuals who were members of the CZD haplogroup showed a significant association with better disease-free survival (DFS) than the other three haplogroups and this phenomenon still existed after adjusting for tumor stage, differentiation and age at diagnosis (hazard ratio = 0.55; 95% CI = 0.36–0.84). In addition, an interaction between membership of the RBF haplogroup and radiotherapy/chemo-radiotherapy in DFS was also identified. The results strongly support the hypothesis that an individual’s haplogroup, by defining their genomic background, plays an important role in tumor behavior and mitochondrially-targeted anticancer drugs are promising future therapeutic approaches. PMID:23185408

  14. Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan

    PubMed Central

    Bilal, Erhan; Rabadan, Raul; Alexe, Gabriela; Fuku, Noriyuki; Ueno, Hitomi; Nishigaki, Yutaka; Fujita, Yasunori; Ito, Masafumi; Arai, Yasumichi; Hirose, Nobuyoshi; Ruckenstein, Andrei; Bhanot, Gyan; Tanaka, Masashi

    2008-01-01

    We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99–105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain “beneficial” patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations. PMID:18545700

  15. Population expansion in the North African Late Pleistocene signalled by mitochondrial DNA haplogroup U6

    PubMed Central

    2010-01-01

    Background The archaeology of North Africa remains enigmatic, with questions of population continuity versus discontinuity taking centre-stage. Debates have focused on population transitions between the bearers of the Middle Palaeolithic Aterian industry and the later Upper Palaeolithic populations of the Maghreb, as well as between the late Pleistocene and Holocene. Results Improved resolution of the mitochondrial DNA (mtDNA) haplogroup U6 phylogeny, by the screening of 39 new complete sequences, has enabled us to infer a signal of moderate population expansion using Bayesian coalescent methods. To ascertain the time for this expansion, we applied both a mutation rate accounting for purifying selection and one with an internal calibration based on four approximate archaeological dates: the settlement of the Canary Islands, the settlement of Sardinia and its internal population re-expansion, and the split between haplogroups U5 and U6 around the time of the first modern human settlement of the Near East. Conclusions A Bayesian skyline plot placed the main expansion in the time frame of the Late Pleistocene, around 20 ka, and spatial smoothing techniques suggested that the most probable geographic region for this demographic event was to the west of North Africa. A comparison with U6's European sister clade, U5, revealed a stronger population expansion at around this time in Europe. Also in contrast with U5, a weak signal of a recent population expansion in the last 5,000 years was observed in North Africa, pointing to a moderate impact of the late Neolithic on the local population size of the southern Mediterranean coast. PMID:21176127

  16. Neolithic mitochondrial haplogroup H genomes and the genetic origins of Europeans

    PubMed Central

    Templeton, Jennifer; Brandt, Guido; Soubrier, Julien; Jane Adler, Christina; Richards, Stephen M.; Der Sarkissian, Clio; Ganslmeier, Robert; Friederich, Susanne; Dresely, Veit; van Oven, Mannis; Kenyon, Rosalie; Van der Hoek, Mark B.; Korlach, Jonas; Luong, Khai; Ho, Simon Y. W.; Quintana-Murci, Lluis; Behar, Doron M.; Meller, Harald; Alt, Kurt W.; Cooper, Alan

    2014-01-01

    Haplogroup (hg) H dominates present-day Western European mitochondrial (mt) DNA variability (>40%), yet was less common (~19%) amongst Early Neolithic farmers (~5450 BC) and virtually absent in Mesolithic hunter-gatherers. Here we investigate this major component of the maternal population history of modern Europeans and sequence 39 complete hg H mitochondrial genomes from ancient human remains. We then compare this ‘real-time’ genetic data with cultural changes taking place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. Our results reveal that the current diversity and distribution of hg H were largely established by the Mid-Neolithic (~4000 BC), but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers expanding out of Iberia in the Late Neolithic (~2800 BC). Dated hg H genomes allow us to reconstruct the recent evolutionary history of hg H and reveal a mutation rate 45% higher than current estimates for human mitochondria. PMID:23612305

  17. The Genetic Diversity of the Nguni Breed of African Cattle (Bos spp.): Complete Mitochondrial Genomes of Haplogroup T1

    PubMed Central

    Horsburgh, K. Ann; Prost, Stefan; Gosling, Anna; Stanton, Jo-Ann; Rand, Christy; Matisoo-Smith, Elizabeth A.

    2013-01-01

    Domesticated cattle were commonplace in northern Africa by about 7,000 years ago. Archaeological evidence, however, suggests they were not established in southern Africa until much later, no earlier than 2,000 years ago. Genetic reconstructions have started to shed light on the movement of African cattle, but efforts have been frustrated by a lack of data south of Ethiopia and the nature of the mitochondrial haplogroup T1 which is almost fixed across the continent. We sequenced 35 complete mitochondrial genomes from a South African herd of Nguni cattle, a breed historically associated with Bantu speaking farmers who were among the first to bring cattle to southern Africa. As expected, all individuals in the study were found to be members of haplogroup T1. Only half of the sub-haplogroups of T1 (T1a-T1f) are represented in our sample and the overwhelming majority (94%) in this study belong to subhaplogroup T1b. A previous study of African cattle found frequencies of T1b of 27% in Egypt and 69% in Ethiopia. These results are consistent with serial multiple founder effects significantly shaping the gene pool as cattle were moved from north to south across the continent. Interestingly, these mitochondrial data give no indication that the impacts of the founder effects were ameliorated by gene flow from recently introduced Indian cattle breeds. PMID:23977187

  18. European Mitochondrial DNA Haplogroups and Metabolic Changes during Antiretroviral Therapy in AIDS Clinical Trials Group Study A5142

    PubMed Central

    Hulgan, Todd; Haubrich, Richard; Riddler, Sharon A.; Tebas, Pablo; Ritchie, Marylyn D.; McComsey, Grace A.; Haas, David W.; Canter, Jeffrey A.

    2010-01-01

    Background Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among A5142 participants. Methods 757 ART-naïve subjects were randomized to one of three class-sparing ART regimens including efavirenz and/or lopinavir/ritonavir with or without nucleoside reverse transcriptase inhibitors (NRTIs). Non-randomized NRTIs included stavudine, tenofovir, or zidovudine, each with lamivudine. Fasting lipid profiles and whole-body dual-energy X-ray absorptiometry (DEXA) were performed. Nine European mtDNA haplogroups were determined for 231 self-identified non-Hispanic white subjects. Metabolic changes from baseline to 96 weeks were analyzed by haplogroup. Results Median age was 39 years, 9% were female, and 37%, 32%, and 30% were randomized to NRTI-containing regimens with either efavirenz or lopinavir/ritonavir, and an NRTI-sparing regimen respectively. Among NRTI-containing regimens, 51% included zidovudine, 28% tenofovir, and 21% stavudine. Compared with other haplogroups, mtDNA haplogroup I (N=10) had higher baseline non-HDL cholesterol (160 mg/dL [interquartile range 137–171] vs. 120 mg/dL [104–136]; p=0.005), a decrease in non-HDL cholesterol over 96 weeks (−14% [−20-+6] vs. +25% [+8-+51]; p<0.001), tended to have more baseline extremity fat, and had more extremity fat loss by DEXA (−13% [−31-+12] vs. +9% [−13-+26]; p=0.08) and lipoatrophy (50% vs. 20%; p=0.04). Haplogroup W (N=5; all randomized to NRTI-sparing regimens) had the greatest increase in extremity fat (+35.5% [+26.8 - +54.9]; P=0.02). Conclusions Lipids and extremity fat were associated with European mtDNA haplogroups in this HIV-infected population. These preliminary results suggest that mitochondrial genomics may influence metabolic parameters before and during ART. PMID:20871389

  19. [The analysis of mitochondrial DNA haplogroups and variants for Leber's hereditary optic neuropathy in Chinese families carrying the m.14484T >C mutation].

    PubMed

    Meng, Xiangjuan; Zhu, Jinping; Gao, Min; Zhang, Sai; Zhao, Fuxin; Zhang, Juanjuan; Liu, Xiaoling; Wei, Qiping; Tong, Yi; Zhang, Minglian; Qu, Jia; Guan, Minxin

    2014-04-01

    The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber's hereditary optic neuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient's mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss. PMID:24846978

  20. Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts.

    PubMed

    Zhang, A-Mei; Hu, Qiu-Xiang; Liu, Feng-Liang; Bi, Rui; Yang, Bi-Qing; Zhang, Wen; Guo, Hao; Logan, Ian; Zheng, Yong-Tang; Yao, Yong-Gang

    2016-08-01

    Drug addiction is one of the most serious social problems in the world today and addicts are always at a high risk of acquiring HIV infection. Mitochondrial impairment has been reported in both drug addicts and in HIV patients undergoing treatment. In this study, we aimed to investigate whether mitochondrial DNA (mtDNA) haplogroup could affect the risk of drug addiction and HIV-1 infection in Chinese. We analyzed mtDNA sequence variations of 577 Chinese intravenous drug addicts (289 with HIV-1 infection and 288 without) and compared with 2 control populations (n = 362 and n = 850). We quantified the viral load in HIV-1-infected patients with and without haplogroup A status and investigated the potential effect of haplogroup A defining variants m.4824A > G and m.8794C > T on the cellular reactive oxygen species (ROS) levels by using an allotopic expression assay. mtDNA haplogroup A had a protective effect against drug addiction but appeared to confer an increased risk of HIV infection in addicts. HIV-1-infected addicts with haplogroup A had a trend for a higher viral load, although the mean viral load was similar between carriers of haplogroup A and those with other haplogroup. Hela cells overexpressing allele m.8794 T showed significantly decreased ROS levels as compared to cells with the allele m.8794C (P = 0.03). Our results suggested that mtDNA haplogroup A might protect against drug addiction but increase the risk of HIV-1 infection. The contradictory role of haplogroup A might be caused by an alteration in mitochondrial function due to a particular mtDNA ancestral variant. PMID:26162319

  1. In vitro embryo production efficiency in cattle and its association with oocyte adenosine triphosphate content, quantity of mitochondrial DNA, and mitochondrial DNA haplogroup.

    PubMed

    Tamassia, M; Nuttinck, F; May-Panloup, P; Reynier, P; Heyman, Y; Charpigny, G; Stojkovic, M; Hiendleder, S; Renard, J-P; Chastant-Maillard, S

    2004-08-01

    Mitochondria have a broad range of functions that affect reproduction, and structural as well as quantitative variation in mtDNA has been associated with gamete quality and reproductive success. To investigate the mitochondria effect on in vitro embryo production, we collected oocytes by ultrasound-guided follicular aspiration from donor cows known to differ in the developmental capacity, measured by the blastocyst formation rate, of their oocytes. To evaluate the potential effects of mtDNA and mitochondrial function on oocyte quality, the donor cows' mtDNA control region was sequenced and, after pairwise comparisons of polymorphisms, animals were grouped into two major haplogroups. The number of mtDNA molecules per oocyte was quantified by real-time PCR, and the adenosine triphosphate (ATP) content was measured in each oocyte to identify variations between haplogroups. Overall, ATP stocks in oocytes of the two haplogroups differed significantly (P < 0.05; means +/- SEM) both at the germinal vesicle and metaphase II stages (2.8 +/- 0.06 pmol vs. 2.6 +/- 0.07 pmol and 2.9 +/- 0.1 pmol vs. 2.3 +/- 0.06 pmol, respectively). The proportion of development to blastocyst was significantly different between haplogroups (22.3 +/- 2.1 % vs. 36.7 +/- 2.9 %). The number of mtDNA molecules per oocyte was highly variable (377 327 +/- 14 104, ranging from 2.0 x 10(3) to 1.2 x 10(6)) but not significantly different between the two haplogroups; significant differences were observed between animals without any apparent relationship to blastocyst production. These data suggest that mitochondria and mtDNA haplogroup affect the developmental capacity of bovine oocytes in vitro. PMID:15084486

  2. Reduced-Median-Network Analysis of Complete Mitochondrial DNA Coding-Region Sequences for the Major African, Asian, and European Haplogroups

    PubMed Central

    Herrnstadt, Corinna; Elson, Joanna L.; Fahy, Eoin; Preston, Gwen; Turnbull, Douglass M.; Anderson, Christen; Ghosh, Soumitra S.; Olefsky, Jerrold M.; Beal, M. Flint; Davis, Robert E.; Howell, Neil

    2002-01-01

    The evolution of the human mitochondrial genome is characterized by the emergence of ethnically distinct lineages or haplogroups. Nine European, seven Asian (including Native American), and three African mitochondrial DNA (mtDNA) haplogroups have been identified previously on the basis of the presence or absence of a relatively small number of restriction-enzyme recognition sites or on the basis of nucleotide sequences of the D-loop region. We have used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups. A total of 497 haplogroup-associated polymorphisms were identified, 323 (65%) of which were associated with one haplogroup and 174 (35%) of which were associated with two or more haplogroups. Approximately one-half of these polymorphisms are reported for the first time here. Our results confirm and substantially extend the phylogenetic relationships among mitochondrial genomes described elsewhere from the major human ethnic groups. Another important result is that there were numerous instances both of parallel mutations at the same site and of reversion (i.e., homoplasy). It is likely that homoplasy in the coding region will confound evolutionary analysis of small sequence sets. By a linkage-disequilibrium approach, additional evidence for the absence of human mtDNA recombination is presented here. PMID:11938495

  3. Mitochondrial haplogroup N1a phylogeography, with implication to the origin of European farmers

    PubMed Central

    2010-01-01

    Background Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations. Results The geographic origin and expansion of farmer lineages related N1a subclades have been deduced from combined analysis of 19 complete sequences with 166 N1a haplotypes. The phylogeographic analysis revealed that the central European farmer lineages have originated from different sources: from eastern Europe, local central Europe, and from the Near East via southern Europe. Conclusions The results obtained emphasize that the arrival of central European farmer lineages did not occur via a single demic diffusion event from the Near East at the onset of the Neolithic spread of agriculture into Europe. Indeed these results indicate that the Neolithic transition process was more complex in central Europe and possibly the farmer N1a lineages were a result of a 'leapfrog' colonization process. PMID:20939899

  4. Nuclear and mitochondrial genetic structure in the Eurasian beaver (Castor fiber) – implications for future reintroductions

    PubMed Central

    Senn, Helen; Ogden, Rob; Frosch, Christiane; Syrůčková, Alena; Campbell-Palmer, Roisin; Munclinger, Pavel; Durka, Walter; Kraus, Robert H S; Saveljev, Alexander P; Nowak, Carsten; Stubbe, Annegret; Stubbe, Michael; Michaux, Johan; Lavrov, Vladimir; Samiya, Ravchig; Ulevicius, Alius; Rosell, Frank

    2014-01-01

    Many reintroduction projects for conservation fail, and there are a large number of factors that may contribute to failure. Genetic analysis can be used to help stack the odds of a reintroduction in favour of success, by conducting assessment of source populations to evaluate the possibility of inbreeding and outbreeding depression and by conducting postrelease monitoring. In this study, we use a panel of 306 SNP (single nucleotide polymorphism) markers and 487–489 base pairs of mitochondrial DNA control region sequence data to examine 321 individuals from possible source populations of the Eurasian beaver for a reintroduction to Scotland. We use this information to reassess the phylogenetic history of the Eurasian beavers, to examine the genetic legacy of past reintroductions on the Eurasian landmass and to assess the future power of the genetic markers to conduct ongoing monitoring via parentage analysis and individual identification. We demonstrate the capacity of medium density genetic data (hundreds of SNPs) to provide information suitable for applied conservation and discuss the difficulty of balancing the need for high genetic diversity against phylogenetic best fit when choosing source population(s) for reintroduction. PMID:25067948

  5. Nuclear and mitochondrial genetic structure in the Eurasian beaver (Castor fiber) - implications for future reintroductions.

    PubMed

    Senn, Helen; Ogden, Rob; Frosch, Christiane; Syrůčková, Alena; Campbell-Palmer, Roisin; Munclinger, Pavel; Durka, Walter; Kraus, Robert H S; Saveljev, Alexander P; Nowak, Carsten; Stubbe, Annegret; Stubbe, Michael; Michaux, Johan; Lavrov, Vladimir; Samiya, Ravchig; Ulevicius, Alius; Rosell, Frank

    2014-06-01

    Many reintroduction projects for conservation fail, and there are a large number of factors that may contribute to failure. Genetic analysis can be used to help stack the odds of a reintroduction in favour of success, by conducting assessment of source populations to evaluate the possibility of inbreeding and outbreeding depression and by conducting postrelease monitoring. In this study, we use a panel of 306 SNP (single nucleotide polymorphism) markers and 487-489 base pairs of mitochondrial DNA control region sequence data to examine 321 individuals from possible source populations of the Eurasian beaver for a reintroduction to Scotland. We use this information to reassess the phylogenetic history of the Eurasian beavers, to examine the genetic legacy of past reintroductions on the Eurasian landmass and to assess the future power of the genetic markers to conduct ongoing monitoring via parentage analysis and individual identification. We demonstrate the capacity of medium density genetic data (hundreds of SNPs) to provide information suitable for applied conservation and discuss the difficulty of balancing the need for high genetic diversity against phylogenetic best fit when choosing source population(s) for reintroduction. PMID:25067948

  6. Merging and comparing three mitochondrial markers for phylogenetic studies of Eurasian reindeer (Rangifer tarandus).

    PubMed

    Kvie, Kjersti S; Heggenes, Jan; Røed, Knut H

    2016-07-01

    Phylogenetic analyses provide information that can be useful in the conservation of genetic variation by identifying intraspecific genetic structure. Reconstruction of phylogenetic relationships requires the use of markers with the appropriate amount of variation relative to the timeframe and purpose of the study. Here, genetic structure and clustering are inferred from comparative analyses of three widely used mitochondrial markers, the CR, cytb and the COI region, merged and separately, using Eurasian reindeer as a model. A Bayesian phylogeny and a MJ network, both based on the merged dataset, indicate several distinct maternal haplotype clusters within Eurasian reindeer. In addition to confirm previously described clusters, two new subclusters were found. When comparing the results from the merged dataset with the results from analyses of the three markers separately, similar clustering was found in the CR and COI phylogenies, whereas the cytb region showed poor resolution. Phylogenetic analyses of the merged dataset and the CR revealed congruent results, implying that single sequencing analysis of the CR is an applicable method for studying the haplotype structure in Eurasian reindeer. PMID:27386080

  7. Association of Genes, Pathways, and Haplogroups of the Mitochondrial Genome with the Risk of Colorectal Cancer: The Multiethnic Cohort

    PubMed Central

    Li, Yuqing; Beckman, Kenneth B.; Caberto, Christian; Kazma, Remi; Lum-Jones, Annette; Haiman, Christopher A.; Marchand, Loïc Le; Stram, Daniel O.; Saxena, Richa; Cheng, Iona

    2015-01-01

    The mitochondrial genome encodes for the synthesis of 13 proteins that are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process, and promoting the production of reactive oxidative species. To investigate the role of the OXPHOS pathway and mitochondrial genes in colorectal cancer (CRC) risk, we tested 185 mitochondrial SNPs (mtSNPs), located in 13 genes that comprise four complexes of the OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,453 colorectal cancer cases and 11,930 controls from the Multiethnic Cohort Study. Using the sequence kernel association test, we examined the collective set of 185 mtSNPs, as well as subsets of mtSNPs grouped by mitochondrial pathways, complexes, and genes, adjusting for age, sex, principal components of global ancestry, and self-reported maternal race/ethnicity. We also tested for haplogroup associations using unconditional logistic regression, adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with CRC risk (P = 0.04). In mtSNP-subset analysis, the NADH dehydrogenase 2 (MT-ND2) gene in Complex I was associated with CRC risk at a P-value of 0.001 (q = 0.015). In addition, haplogroup T was associated with CRC risk (OR = 1.66, 95% CI: 1.19–2.33, P = 0.003). No significant mitochondrial pathway and gene associations were observed in the remaining four racial/ethnic groups—African Americans, Asian Americans, Latinos, and Native Hawaiians. In summary, our findings suggest that variations in the mitochondrial genome and particularly in the MT-ND2 gene may play a role in CRC risk among European Americans, but not in other maternal racial/ethnic groups. Further replication is warranted and future

  8. Association of Genes, Pathways, and Haplogroups of the Mitochondrial Genome with the Risk of Colorectal Cancer: The Multiethnic Cohort.

    PubMed

    Li, Yuqing; Beckman, Kenneth B; Caberto, Christian; Kazma, Remi; Lum-Jones, Annette; Haiman, Christopher A; Le Marchand, Loïc; Stram, Daniel O; Saxena, Richa; Cheng, Iona

    2015-01-01

    The mitochondrial genome encodes for the synthesis of 13 proteins that are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process, and promoting the production of reactive oxidative species. To investigate the role of the OXPHOS pathway and mitochondrial genes in colorectal cancer (CRC) risk, we tested 185 mitochondrial SNPs (mtSNPs), located in 13 genes that comprise four complexes of the OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,453 colorectal cancer cases and 11,930 controls from the Multiethnic Cohort Study. Using the sequence kernel association test, we examined the collective set of 185 mtSNPs, as well as subsets of mtSNPs grouped by mitochondrial pathways, complexes, and genes, adjusting for age, sex, principal components of global ancestry, and self-reported maternal race/ethnicity. We also tested for haplogroup associations using unconditional logistic regression, adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with CRC risk (P = 0.04). In mtSNP-subset analysis, the NADH dehydrogenase 2 (MT-ND2) gene in Complex I was associated with CRC risk at a P-value of 0.001 (q = 0.015). In addition, haplogroup T was associated with CRC risk (OR = 1.66, 95% CI: 1.19-2.33, P = 0.003). No significant mitochondrial pathway and gene associations were observed in the remaining four racial/ethnic groups--African Americans, Asian Americans, Latinos, and Native Hawaiians. In summary, our findings suggest that variations in the mitochondrial genome and particularly in the MT-ND2 gene may play a role in CRC risk among European Americans, but not in other maternal racial/ethnic groups. Further replication is warranted and future studies

  9. The analysis of mitochondrial DNA haplogroups and variants for in vitro fertilization failure in a Han Chinese population.

    PubMed

    Mao, Genhong; Lu, Ping; Huang, Xiao-Hui; Wang, Wu-Liang; Tao, Shi-Bo; Li, Qian; Wang, Xiao-Ling; Wang, Ya-Nan

    2016-07-01

    In this study, we aimed to investigate the associations of mitochondrial DNA (mtDNA) haplogroups and variants with in vitro fertilization (IVF) failure. A retrospective, comparative study of 260 fresh IVF cycles in a Han Chinese population was performed from July 2011 to April 2014. Seventy-three couples had low fertilization rates (≤30%) or total fertilization failure, and 187 controls with normal fertilization were included. Human sperm mtDNA haplogroups and variants were determined by polymerase chain reaction (PCR), nested PCR and direct sequencing. One unreported point variant, A15397G, and two novel deletions at positions 8270-8278 and 8276-8284 were found in this study. A homozygous variant, G9053A in MT-ATP6, was detected in 4 of the 73 cases with fertilization failure, whereas this substitution was not detected in the control group (p < 0.01). The frequency of the point 10397 homozygous variant in MT-ND3 in the IVF failure group was markedly lower than that in the control group (p < 0.05). Furthermore, this study showed that the frequencies of point 8701 and 8943 heterozygous variants in MT-ATP6 in the IVF failure group were also markedly lower than those in the control group (p < 0.05). In addition, the frequency of haplogroup Z was markedly higher in the IVF failure group than in the control group (p < 0.05). Our results suggested that MT-ATP6 variants might be possible causes of IVF failure, but the 10397 homozygous variant in MT-ND3 might help decrease the risk of developing IVF failure. Furthermore, this study indicated that men with haplogroup Z might inherit a higher risk of IVF failure in the Han Chinese population. PMID:26242719

  10. New Population and Phylogenetic Features of the Internal Variation within Mitochondrial DNA Macro-Haplogroup R0

    PubMed Central

    Cerezo, Maria; Quintáns, Beatriz; Zarrabeitia, Maria Teresa; Cuscó, Ivon; Lareu, Maria Victoria; García, Óscar; Pérez-Jurado, Luis; Carracedo, Ángel; Salas, Antonio

    2009-01-01

    Background R0 embraces the most common mitochondrial DNA (mtDNA) lineage in West Eurasia, namely, haplogroup H (∼40%). R0 sub-lineages are badly defined in the control region and therefore, the analysis of diagnostic coding region polymorphisms is needed in order to gain resolution in population and medical studies. Methodology/Principal Findings We sequenced the first hypervariable segment (HVS-I) of 518 individuals from different North Iberian regions. The mtDNAs belonging to R0 (∼57%) were further genotyped for a set of 71 coding region SNPs characterizing major and minor branches of R0. We found that the North Iberian Peninsula shows moderate levels of population stratification; for instance, haplogroup V reaches the highest frequency in Cantabria (north-central Iberia), but lower in Galicia (northwest Iberia) and Catalonia (northeast Iberia). When compared to other European and Middle East populations, haplogroups H1, H3 and H5a show frequency peaks in the Franco-Cantabrian region, declining from West towards the East and South Europe. In addition, we have characterized, by way of complete genome sequencing, a new autochthonous clade of haplogroup H in the Basque country, named H2a5. Its coalescence age, 15.6±8 thousand years ago (kya), dates to the period immediately after the Last Glacial Maximum (LGM). Conclusions/Significance In contrast to other H lineages that experienced re-expansion outside the Franco-Cantabrian refuge after the LGM (e.g. H1 and H3), H2a5 most likely remained confined to this area till present days. PMID:19340307

  11. Two families with Leber's hereditary optic neuropathy carrying G11778A and T14502C mutations with haplogroup H2a2a1 in mitochondrial DNA.

    PubMed

    Qiao, Chen; Wei, Tanwei; Hu, Bo; Peng, Chunyan; Qiu, Xueping; Wei, Li; Yan, Ming

    2015-08-01

    The mitochondrial haplogroup has been reported to affect the clinical expression of Leber's hereditary optic neuropathy (LHON). The present study aimed to investigate the interaction between mutations and the haplogroup of mitochondrial DNA (mtDNA) in families. Two unrelated families with LHON were enrolled in the study, and clinical, genetic and molecular characterizations were determined in the affected and unaffected family members. Polymerase chain reaction direct sequencing was performed using 24 pairs of overlapping primers for whole mtDNA to screen for mutations and haplogroup. Bioinformatics analysis was performed to evaluate the pathogenic effect of these mtDNA mutations and the haplogroup. The G11778A mutation was identified in the two families. In addition, the members of family 2 exhibited the T14502C mutation and those in family 1 exhibited the T3394C and T14502C mutations, which were regarded as secondary mutations. The penetrance of visual loss in families 1 and 2 were 30.8 and 33.3%, respectively. In addition, the two families were found to be in the H2a2a1 haplogroup. In this limited sample size, it was demonstrated that the H2a2a1 haplogroup had a possible protective effect against LHON. Additional modifying factors, including environmental factors, lifestyle, estrogen levels and nuclear genes may also be important in LHON. PMID:25936877

  12. Mitochondrial Genetic Diversity of Eurasian Red Squirrels (Sciurus vulgaris) from Denmark.

    PubMed

    Madsen, Corrie L; Vilstrup, Julia T; Fernández, Ruth; Marchi, Nina; Håkansson, Bo; Krog, Mogens; Asferg, Tommy; Baagøe, Hans; Orlando, Ludovic

    2015-01-01

    Melanistic Eurasian red squirrels Sciurus vulgaris are commonly found on the Danish island of Funen. They are thought to represent native Danish squirrel types and are presently under threat from admixture with introduced red squirrels. In response, a conservation program was started in 2009 that involves the translocation of melanistic squirrels from Funen to the squirrel-free island of Langeland. Using mitochondrial DNA of 101 historical and modern samples from throughout Denmark, we assess for the first time population structure and mitochondrial genetic diversity of Danish squirrels compared to its larger pan-Eurasian distribution. We find that Danish squirrels have low levels of genetic diversity, especially melanistic individuals. Bayesian skyline reconstructions show that Danish squirrels have most probably experienced a severe bottleneck within the last 200 years. Also, fine-scale genetic structure was found between squirrels from the regions of Funen, Zealand and Jutland, which mimics the insular geography of Denmark. Additional nuclear DNA analyses will be required to determine the precise admixture levels between original Danish and introduced squirrels and to locate unmixed candidate populations for specific conservation efforts. PMID:26519513

  13. Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

    PubMed Central

    Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

    2009-01-01

    Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants

  14. Phylogeography of the human mitochondrial haplogroup L3e: a snapshot of African prehistory and Atlantic slave trade.

    PubMed

    Bandelt, H J; Alves-Silva, J; Guimarães, P E; Santos, M S; Brehm, A; Pereira, L; Coppa, A; Larruga, J M; Rengo, C; Scozzari, R; Torroni, A; Prata, M J; Amorim, A; Prado, V F; Pena, S D

    2001-11-01

    The mtDNA haplogroup L3e, which is identified by the restriction site +2349 MboI within the Afro-Eurasian superhaplogroup L3 (-3592 HpaI), is omnipresent in Africa but virtually absent in Eurasia (except for neighbouring areas with limited genetic exchange). L3e was hitherto poorly characterised in terms of HVS-I motifs, as the ancestral HVS-I type of L3e cannot be distinguished from the putative HVS-I ancestor of the entire L3 (differing from the CRS by a transition at np 16223). An MboI screening at np 2349 of a large number of Brazilian and Caribbean mtDNAs (encompassing numerous mtDNAs of African ancestry), now reveals that L3e is subdivided into four principal clades, each characterised by a single mutation in HVS-I, with additional support coming from HVS-II and partial RFLP analysis. The apparently oldest of these clades (transition at np 16327) occurs mainly in central Africa and was probably carried to southern Africa with the Bantu expansion(s). The most frequent clade (transition at np 16320) testifies to a pronounced expansion event in the mid-Holocene and seems to be prominent in many Bantu groups from all of Africa. In contrast, one clade (transition at np 16264) is essentially restricted to Atlantic western Africa (including Cabo Verde). We propose a tentative L3e phylogeny that is based on 197 HVS-I sequences. We conclude that haplogroup L3e originated in central or eastern Africa about 46,000 (+/-14,000) years ago, and was a hitchhiker of much later dispersal and local expansion events, with the rise of food production and iron smelting. Enforced migration of African slaves to the Americas translocated L3e mitochondria, the descendants of which in Brazil and the Caribbean still reflect their different regional African ancestries. PMID:11851985

  15. Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

    PubMed Central

    Santoro, Aurelia; Balbi, Valentina; Balducci, Elisa; Pirazzini, Chiara; Rosini, Francesca; Tavano, Francesca; Achilli, Alessandro; Siviero, Paola; Minicuci, Nadia; Bellavista, Elena; Mishto, Michele; Salvioli, Stefano; Marchegiani, Francesca; Cardelli, Maurizio; Olivieri, Fabiola; Nacmias, Benedetta; Chiamenti, Andrea Maria; Benussi, Luisa; Ghidoni, Roberta; Rose, Giuseppina; Gabelli, Carlo; Binetti, Giuliano; Sorbi, Sandro; Crepaldi, Gaetano; Passarino, Giuseppe; Torroni, Antonio; Franceschi, Claudio

    2010-01-01

    Background Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. Methodology/Principal Findings We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR = 1.85, 95% CI:1.04–3.23) in particular for females (OR = 2.19, 95% CI:1.06–4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p = 0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p = 0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. Conclusions Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups

  16. Assessment of the Relationship between Self-Declared Ethnicity, Mitochondrial Haplogroups and Genomic Ancestry in Brazilian Individuals

    PubMed Central

    Cardena, Mari M. S. G.; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Mansur, Alfredo J.; Pereira, Alexandre C.; Fridman, Cintia

    2013-01-01

    In populations that have a high degree of admixture, such as in Brazil, the sole use of ethnicity self-declaration information is not a good method for classifying individuals regarding their ethnicity. Here, we evaluate the relationship of self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of the mitochondrial DNA (mtDNA), and the genomic ancestry was obtained using 48 autosomal insertion-deletion ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as White, 13.8% as Brown and 10.4% as Black. Classification of the mtDNA haplogroups showed that 46.3% had African mtDNA, and the genomic ancestry analysis showed that the main contribution was European (57.4%). When we looked at the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities from 367 individuals who self-declared as White, 37.6% showed African mtDNA, and they had a high contribution of European genomic ancestry (63.3%) but also a significant contribution of African ancestry (22.2%). Of the 68 individuals who self-declared as Brown, 25% showed Amerindian mtDNA and similar contribution of European and African genomic ancestries. Of the 51 subjects who self-declared as black, 80.4% had African mtDNA, and the main contribution of genomic ancestry was African (55.6%), but they also had a significant proportion of European ancestry (32.1%). The Brazilian population had a uniform degree of Amerindian genomic ancestry, and it was only with the use of genetic markers (autosomal or mitochondrial) that we were able to capture Amerindian ancestry information. Additionally, it was possible to observe a high degree of heterogeneity in the ancestry for both types of genetic markers, which shows the high genetic admixture that is present in the Brazilian population. We suggest that in epidemiological studies, the use

  17. Genetic differences between Chibcha and Non-Chibcha speaking tribes based on mitochondrial DNA (mtDNA) haplogroups from 21 Amerindian tribes from Colombia

    PubMed Central

    Usme-Romero, Solangy; Alonso, Milena; Hernandez-Cuervo, Helena; Yunis, Emilio J.; Yunis, Juan J.

    2013-01-01

    We analyzed the frequency of four mitochondrial DNA haplogroups in 424 individuals from 21 Colombian Amerindian tribes. Our results showed a high degree of mtDNA diversity and genetic heterogeneity. Frequencies of mtDNA haplogroups A and C were high in the majority of populations studied. The distribution of these four mtDNA haplogroups from Amerindian populations was different in the northern region of the country compared to those in the south. Haplogroup A was more frequently found among Amerindian tribes in northern Colombia, while haplogroup D was more frequent among tribes in the south. Haplogroups A, C and D have clinal tendencies in Colombia and South America in general. Populations belonging to the Chibcha linguistic family of Colombia and other countries nearby showed a strong genetic differentiation from the other populations tested, thus corroborating previous findings. Genetically, the Ingano, Paez and Guambiano populations are more closely related to other groups of south eastern Colombia, as also inferred from other genetic markers and from archeological data. Strong evidence for a correspondence between geographical and linguistic classification was found, and this is consistent with evidence that gene flow and the exchange of customs and knowledge and language elements between groups is facilitated by close proximity. PMID:23885195

  18. Mitochondrial haplogroup U5b3: a distant echo of the epipaleolithic in Italy and the legacy of the early Sardinians.

    PubMed

    Pala, Maria; Achilli, Alessandro; Olivieri, Anna; Hooshiar Kashani, Baharak; Perego, Ugo A; Sanna, Daria; Metspalu, Ene; Tambets, Kristiina; Tamm, Erika; Accetturo, Matteo; Carossa, Valeria; Lancioni, Hovirag; Panara, Fausto; Zimmermann, Bettina; Huber, Gabriela; Al-Zahery, Nadia; Brisighelli, Francesca; Woodward, Scott R; Francalacci, Paolo; Parson, Walther; Salas, Antonio; Behar, Doron M; Villems, Richard; Semino, Ornella; Bandelt, Hans-Jürgen; Torroni, Antonio

    2009-06-01

    There are extensive data indicating that some glacial refuge zones of southern Europe (Franco-Cantabria, Balkans, and Ukraine) were major genetic sources for the human recolonization of the continent at the beginning of the Holocene. Intriguingly, there is no genetic evidence that the refuge area located in the Italian Peninsula contributed to this process. Here we show, through phylogeographic analyses of mitochondrial DNA (mtDNA) variation performed at the highest level of molecular resolution (52 entire mitochondrial genomes), that the most likely homeland for U5b3-a haplogroup present at a very low frequency across Europe-was the Italian Peninsula. In contrast to mtDNA haplogroups that expanded from other refugia, the Holocene expansion of haplogroup U5b3 toward the North was restricted by the Alps and occurred only along the Mediterranean coasts, mainly toward nearby Provence (southern France). From there, approximately 7,000-9,000 years ago, a subclade of this haplogroup moved to Sardinia, possibly as a result of the obsidian trade that linked the two regions, leaving a distinctive signature in the modern people of the island. This scenario strikingly matches the age, distribution, and postulated geographic source of a Sardinian Y chromosome haplogroup (I2a2-M26), a paradigmatic case in the European context of a founder event marking both female and male lineages. PMID:19500771

  19. Mitochondrial Haplogroup U5b3: A Distant Echo of the Epipaleolithic in Italy and the Legacy of the Early Sardinians

    PubMed Central

    Pala, Maria; Achilli, Alessandro; Olivieri, Anna; Kashani, Baharak Hooshiar; Perego, Ugo A.; Sanna, Daria; Metspalu, Ene; Tambets, Kristiina; Tamm, Erika; Accetturo, Matteo; Carossa, Valeria; Lancioni, Hovirag; Panara, Fausto; Zimmermann, Bettina; Huber, Gabriela; Al-Zahery, Nadia; Brisighelli, Francesca; Woodward, Scott R.; Francalacci, Paolo; Parson, Walther; Salas, Antonio; Behar, Doron M.; Villems, Richard; Semino, Ornella; Bandelt, Hans-Jürgen; Torroni, Antonio

    2009-01-01

    There are extensive data indicating that some glacial refuge zones of southern Europe (Franco-Cantabria, Balkans, and Ukraine) were major genetic sources for the human recolonization of the continent at the beginning of the Holocene. Intriguingly, there is no genetic evidence that the refuge area located in the Italian Peninsula contributed to this process. Here we show, through phylogeographic analyses of mitochondrial DNA (mtDNA) variation performed at the highest level of molecular resolution (52 entire mitochondrial genomes), that the most likely homeland for U5b3—a haplogroup present at a very low frequency across Europe—was the Italian Peninsula. In contrast to mtDNA haplogroups that expanded from other refugia, the Holocene expansion of haplogroup U5b3 toward the North was restricted by the Alps and occurred only along the Mediterranean coasts, mainly toward nearby Provence (southern France). From there, ∼7,000–9,000 years ago, a subclade of this haplogroup moved to Sardinia, possibly as a result of the obsidian trade that linked the two regions, leaving a distinctive signature in the modern people of the island. This scenario strikingly matches the age, distribution, and postulated geographic source of a Sardinian Y chromosome haplogroup (I2a2-M26), a paradigmatic case in the European context of a founder event marking both female and male lineages. PMID:19500771

  20. An Alternative Model for the Early Peopling of Southern South America Revealed by Analyses of Three Mitochondrial DNA Haplogroups

    PubMed Central

    de Saint Pierre, Michelle; Bravi, Claudio M.; Motti, Josefina M. B.; Fuku, Noriyuki; Tanaka, Masashi; Llop, Elena; Bonatto, Sandro L.; Moraga, Mauricio

    2012-01-01

    After several years of research, there is now a consensus that America was populated from Asia through Beringia, probably at the end of the Pleistocene. But many details such as the timing, route(s), and origin of the first settlers remain uncertain. In the last decade genetic evidence has taken on a major role in elucidating the peopling of the Americas. To study the early peopling of South America, we sequenced the control region of mitochondrial DNA from 300 individuals belonging to indigenous populations of Chile and Argentina, and also obtained seven complete mitochondrial DNA sequences. We identified two novel mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together with the recently described D1g sub-haplogroup have locally high frequencies and are basically restricted to populations from the extreme south of South America. The estimated ages of D1g and B2l, about ∼15,000 years BP, together with their similar population dynamics and the high haplotype diversity shown by the networks, suggests that they probably appeared soon after the arrival of the first settlers and agrees with the dating of the earliest archaeological sites in South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup, D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces our hypothesis of the continuity of the current Patagonian populations with the initial founders. Our results indicate that the extant native populations inhabiting South Chile and Argentina are a group which had a common origin, and suggest a population break between the extreme south of South America and the more northern part of the continent. Thus the early colonization process was not just an expansion from north to south, but also included movements across the Andes. PMID:22970129

  1. Mitochondrial Genome Sequencing in Mesolithic North East Europe Unearths a New Sub-Clade within the Broadly Distributed Human Haplogroup C1

    PubMed Central

    Der Sarkissian, Clio; Brotherton, Paul; Balanovsky, Oleg; Templeton, Jennifer E. L.; Llamas, Bastien; Soubrier, Julien; Moiseyev, Vyacheslav; Khartanovich, Valery; Cooper, Alan; Haak, Wolfgang

    2014-01-01

    The human mitochondrial haplogroup C1 has a broad global distribution but is extremely rare in Europe today. Recent ancient DNA evidence has demonstrated its presence in European Mesolithic individuals. Three individuals from the 7,500 year old Mesolithic site of Yuzhnyy Oleni Ostrov, Western Russia, could be assigned to haplogroup C1 based on mitochondrial hypervariable region I sequences. However, hypervariable region I data alone could not provide enough resolution to establish the phylogenetic relationship of these Mesolithic haplotypes with haplogroup C1 mitochondrial DNA sequences found today in populations of Europe, Asia and the Americas. In order to obtain high-resolution data and shed light on the origin of this European Mesolithic C1 haplotype, we target-enriched and sequenced the complete mitochondrial genome of one Yuzhnyy Oleni Ostrov C1 individual. The updated phylogeny of C1 haplogroups indicated that the Yuzhnyy Oleni Ostrov haplotype represents a new distinct clade, provisionally coined “C1f”. We show that all three C1 carriers of Yuzhnyy Oleni Ostrov belong to this clade. No haplotype closely related to the C1f sequence could be found in the large current database of ancient and present-day mitochondrial genomes. Hence, we have discovered past human mitochondrial diversity that has not been observed in modern-day populations so far. The lack of positive matches in modern populations may be explained by under-sampling of rare modern C1 carriers or by demographic processes, population extinction or replacement, that may have impacted on populations of Northeast Europe since prehistoric times. PMID:24503968

  2. The Background of Mitochondrial DNA Haplogroup J Increases the Sensitivity of Leber's Hereditary Optic Neuropathy Cells to 2,5-Hexanedione Toxicity

    PubMed Central

    Ghelli, Anna; Porcelli, Anna Maria; Zanna, Claudia; Vidoni, Sara; Mattioli, Stefano; Barbieri, Anna; Iommarini, Luisa; Pala, Maria; Achilli, Alessandro; Torroni, Antonio; Rugolo, Michela; Carelli, Valerio

    2009-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for

  3. 60,000 years of interactions between Central and Eastern Africa documented by major African mitochondrial haplogroup L2

    PubMed Central

    Silva, Marina; Alshamali, Farida; Silva, Paula; Carrilho, Carla; Mandlate, Flávio; Jesus Trovoada, Maria; Černý, Viktor; Pereira, Luísa; Soares, Pedro

    2015-01-01

    Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is nowadays spread across the entire continent. L2 movements were previously postulated to be related to the Bantu expansion, but L2 expansions eastwards probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new complete sequences) we provide insights on the complex net of within-African migrations in the last 60 thousand years (ka). Results show that lineages in Southern Africa cluster with Western/Central African lineages at a recent time scale, whereas, eastern lineages seem to be substantially more ancient. Three moments of expansion from a Central African source are associated to L2: (1) one migration at 70–50 ka into Eastern or Southern Africa, (2) postglacial movements (15–10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last 5 ka. The complementary population and L0a phylogeography analyses indicate no strong evidence of mtDNA gene flow between eastern and southern populations during the later movement, suggesting low admixture between Eastern African populations and the Bantu migrants. This implies that, at least in the early stages, the Bantu expansion was mainly a demic diffusion with little incorporation of local populations. PMID:26211407

  4. 60,000 years of interactions between Central and Eastern Africa documented by major African mitochondrial haplogroup L2.

    PubMed

    Silva, Marina; Alshamali, Farida; Silva, Paula; Carrilho, Carla; Mandlate, Flávio; Jesus Trovoada, Maria; Černý, Viktor; Pereira, Luísa; Soares, Pedro

    2015-01-01

    Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is nowadays spread across the entire continent. L2 movements were previously postulated to be related to the Bantu expansion, but L2 expansions eastwards probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new complete sequences) we provide insights on the complex net of within-African migrations in the last 60 thousand years (ka). Results show that lineages in Southern Africa cluster with Western/Central African lineages at a recent time scale, whereas, eastern lineages seem to be substantially more ancient. Three moments of expansion from a Central African source are associated to L2: (1) one migration at 70-50 ka into Eastern or Southern Africa, (2) postglacial movements (15-10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last 5 ka. The complementary population and L0a phylogeography analyses indicate no strong evidence of mtDNA gene flow between eastern and southern populations during the later movement, suggesting low admixture between Eastern African populations and the Bantu migrants. This implies that, at least in the early stages, the Bantu expansion was mainly a demic diffusion with little incorporation of local populations. PMID:26211407

  5. Mitochondrial DNA control region haplotype and haplogroup diversity in South Eastern Turkey.

    PubMed

    Serin, Ayse; Canan, Husniye; Alper, Behnan; Korkut Gulmen, Mete; Zimmermann, Bettina; Parson, Walther

    2016-09-01

    Despite its large geographic and population size only little is known about the mitochondrial (mt)DNA make up of Turkey.orensically relevant data are almost completely absent in the literature. We analyzed the mtDNA control region of 224 volunteers from South Eastern Turkey and compared the data to populations from neighboring countries. The haplotypes will be made available via the EMPOP database (EMP00670) and contribute to the body of forensic mtDNA data. PMID:27479879

  6. Mitochondrial DNA evidence of southward migration of Manchus in China.

    PubMed

    Zhao, Yong-Bin; Sun, Wen-Yi; Zhan, Yang; Di, Wang; Yu, Chang-Chun

    2011-01-01

    The Northeast area of China is a cross region between East Asia and Siberia. Although five populations from this area have been studied in maternal lineage, little is known about the genetics of other populations. In this study, forty-seven Manchu individuals were analyzed using a mitochondrial DNA marker, and fourteen mitochondrial DNA haplogroups, the representative haplogroups of east Eurasian, were identified. All analyses showed that Manchu were close to the neighboring populations such as Mongolian, Korean and northern Han Chinese, and were far from the other populations who lived in the cradle of Manchu, suggesting that the Manchu integrated gradually with natives following its southward migration. PMID:22393778

  7. Phylogenetic relationship of Eurasian lynx (Lynx lynx) revealed by complete mitochondrial genome.

    PubMed

    Ning, Yao; Liu, Hui; Jiang, Guangshun; Ma, Jianzhang

    2016-09-01

    The Eurasian lynx (Lynx lynx) is an Endangered species in northeast China. We first obtained muscle sample, extracted the sample DNA and sequenced the whole mtDNA genome of lynx from northeast China. We reconstructed the phylogenetic tree of Eurasian lynx and 10 other most closely related Felidae species. This lynx's complete mitogenome is 17 054bp in length, includes 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and one control region. The phylogenetic tree confirmed previous research results. PMID:26195214

  8. Population history of the Red Sea--genetic exchanges between the Arabian Peninsula and East Africa signaled in the mitochondrial DNA HV1 haplogroup.

    PubMed

    Musilová, Eliška; Fernandes, Verónica; Silva, Nuno M; Soares, Pedro; Alshamali, Farida; Harich, Nourdin; Cherni, Lotfi; Gaaied, Amel Ben Ammar El; Al-Meeri, Ali; Pereira, Luísa; Cerný, Viktor

    2011-08-01

    Archaeological studies have revealed cultural connections between the two sides of the Red Sea dating to prehistory. The issue has still not been properly addressed, however, by archaeogenetics. We focus our attention here on the mitochondrial haplogroup HV1 that is present in both the Arabian Peninsula and East Africa. The internal variation of 38 complete mitochondrial DNA sequences (20 of them presented here for the first time) affiliated into this haplogroup testify to its emergence during the late glacial maximum, most probably in the Near East, with subsequent dispersion via population expansions when climatic conditions improved. Detailed phylogeography of HV1 sequences shows that more recent demographic upheavals likely contributed to their spread from West Arabia to East Africa, a finding concordant with archaeological records suggesting intensive maritime trade in the Red Sea from the sixth millennium BC onwards. Closer genetic exchanges are apparent between the Horn of Africa and Yemen, while Egyptian HV1 haplotypes seem to be more similar to the Near Eastern ones. PMID:21660931

  9. Early Eurasian migration traces in the Tarim Basin revealed by mtDNA polymorphisms.

    PubMed

    Cui, Yinqiu; Li, Chunxiang; Gao, Shizhu; Xie, Chengzhi; Zhou, Hui

    2010-08-01

    The mitochondrial DNA (mtDNA) polymorphisms of 58 samples from the Daheyan village located in the central Taklamakan Desert of the Tarim Basin were determined in this study. Among the 58 samples, 29 haplotypes belonging to 18 different haplogroups were analyzed. Almost all the mtDNAs belong to a subset of either the defined Western or Eastern Eurasian pool. Extensive Eastern Eurasian lineages exist in the Daheyan population in which Northern-prevalent haplogroups present higher frequencies. In the limited existing Western Eurasian lineages, two sub-haplogroups, U3 and X2, that are rare in Central Asia were found in this study, which may be indicative of the remnants of an early immigrant population from the Near East and Caucasus regions preserved only in the Tarim Basin. The presence of U3 in modern and archeological samples in the Tarim Basin suggests that the immigration took place earlier than 2,000 years ago and points to human continuity in this area, with at least one Western lineage originating from the Near East and Caucasus regions. PMID:20091803

  10. Complete mitochondrial genome of the Eurasian flying squirrel Pteromys volans (Sciuromorpha, Sciuridae) and revision of rodent phylogeny.

    PubMed

    Ryu, Shi Hyun; Kwak, Min Jung; Hwang, Ui Wook

    2013-02-01

    In this study, the complete mitochondrial genome of the Eurasian flying squirrel Pteromys volans (Rodentia, Sciuromorpha, Sciuridae) was sequenced and characterized in detail. The entire mitochondrial genome of P. volans consisted of 16,513 bp and contained 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two non-coding regions. Its gene arrangement pattern was consistent with the mammalian ground pattern. The overall base composition and AT contents were similar to those of other rodent mitochondrial genomes. The light-strand origin generally identified between tRNA ( Asn ) and tRNA ( Cys ) consisted of a secondary structure with an 11-bp stem and an 11-bp loop. The large control region was constructed of three characteristic domains, ETAS, CD, and CSB without any repeat sequences. Each domain contained ETAS1, subsequences A, B, and C, and CSB1, respectively. In order to examine phylogenetic contentious issues of the monophyly of rodents and phylogenetic relationships among five rodent suborders, here, phylogenetic analyses based on nucleotide sequence data of the 35 rodent and 3 lagomorph mitochondrial genomes were performed using the Bayesian inference and maximum likelihood method. The result strongly supported the rodent monophyly with high node confidence values (BP 100 % in ML and BPP 1.00 in BI) and also monophylies of four rodent suborders (BP 85-100 % in ML and BPP 1.00 in BI), except for Anomalumorpha in which only one species was examined here. Also, phylogenetic relationships among the five rodent suborders were suggested and discussed in detail. PMID:23114915

  11. Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia

    PubMed Central

    Klütsch, C F C; Seppälä, E H; Fall, T; Uhlén, M; Hedhammar, Å; Lohi, H; Savolainen, P

    2011-01-01

    The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60–100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480–3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage. PMID:20497152

  12. The tRNAMet 4435A>G mutation in the mitochondrial haplogroup G2a1 is responsible for maternally inherited hypertension in a Chinese pedigree

    PubMed Central

    Lu, Zhongqiu; Chen, Hong; Meng, Yanzi; Wang, Yan; Xue, Ling; Zhi, Shaoce; Qiu, Qiaomeng; Yang, Li; Mo, Jun Qin; Guan, Min-Xin

    2011-01-01

    Mutations in mitochondrial DNA (mtDNA) have been associated with hypertension in several pedigrees with maternal inheritance. However, the pathophysiology of maternally inherited hypertension remains poorly understood. We reported here clinical, genetic evaluations and molecular analysis of mtDNA in a three-generation Han Chinese family with essential hypertension. Eight of 17 matrilineal relatives exhibited a wide range of severity in essential hypertension, whereas none of the offsprings of the affected father had hypertension. The age-at-onset of hypertension in the maternal kindred varied from 31 to 65 years, with an average of 52 years. Sequence analysis of mtDNA in this pedigree identified the known homoplasmic 4435A>G mutation, which is located at immediately 3′ end to the anticodon, corresponding to the conventional position 37 of tRNAMet, and 41 variants belonging to the Asian haplogroup G2a1. In contrast, the 4435A>G mutation occurred among mtDNA haplogroups B5a, D, M7a2 and J. The adenine (A37) at this position of tRNAMet is extraordinarily conserved from bacteria to human mitochondria. This modified A37 was shown to contribute to the high fidelity of codon recognition, structural formation and stabilization of functional tRNAs. However, 41 other mtDNA variants in this pedigree were the known polymorphisms. The occurrence of the 4435A>G mutation in two genetically unrelated families affected by hypertension indicates that this mutation is involved in hypertension. Our present investigations further supported our previous findings that the 4435A>G mutation acted as an inherited risk factor for the development of hypertension. Our findings will be helpful for counseling families of maternally inherited hypertension. PMID:21694735

  13. [Analysis of mitochondrial DNA haplotypes in yakut population].

    PubMed

    Fedorova, S A; Bermisheva, M A; Villems, R; Maksimova, N R; Khusnutdinova, E K

    2003-01-01

    To study the mitochondrial gene pool structure in Yakuts, polymorphism of mtDNA hypervariable segment I (16,024-16,390) was analyzed in 191 people sampled from the indigenous population of the Sakha Republic. In total, 67 haplotypes of 14 haplogroups were detected. Most (91.6%) haplotypes belonged to haplogroups A, B, C, D, F, G, M*, and Y, which are specific for East Eurasian ethnic groups; 8.4% haplotypes represented Caucasian haplogroups H, HV1, J, T, U, and W. A high frequency of mtDNA types belonging to Asian supercluster M was peculiar for Yakuts: mtDNA types belonging to haplogroup C, D, or G and undifferentiated mtDNA types of haplogroup M (M*) accounted for 81% of all haplotypes. The highest diversity was observed for haplogroups C and D, which comprised respectively 22 (44%) and 18 (30%) haplotypes. Yakuts showed the lowest genetic diversity (H = 0.964) among all Turkic ethnic groups. Phylogenetic analysis testified to a common genetic substrate of Yakuts, Mongols, and Central Asian (Kazakh, Kyrgyz, Uigur) populations. Yakuts proved to share 21 (55.5%) mtDNA haplogroups with the Central Asian ethnic groups and Mongols. Comparisons with modern paleo-Asian populations (Chukcha, Itelmen, Koryaks) revealed three (8.9%) haplotypes common for Yakuts and Koryaks. The results of mtDNA analysis disagree with the hypothesis of an appreciable paleo-Asian contribution to the modern Yakut gene pool. PMID:12942638

  14. Phylogeography of mitochondrial haplogroup D1: an early spread of subhaplogroup D1j from Central Argentina.

    PubMed

    García, Angelina; Pauro, Maia; Nores, Rodrigo; Bravi, Claudio M; Demarchi, Darío A

    2012-12-01

    We analyzed the patterns of variation of haplogroup D1 in central Argentina, including new data and published information from other populations of South America. Almost 28% (107/388) of the individuals sampled in the region belong to haplogroup D1, whereas more than 52% of them correspond to the recently described subhaplogroup D1j (Bodner et al.: Genome Res 22 (2012) 811-820), defined by the presence of additional transitions at np T152C-C16242T-T16311C to the nodal D1 motif. This lineage was found at high frequencies across a wide territory with marked geographical-ecological differences. Additionally, 12 individuals present the mutation C16187T that defines the recently named subhaplogroup D1g (Bodner et al.: Genome Res 22 (2012) 811-820), previously described in populations of Patagonia and Tierra del Fuego. Based on our results and additional data already published, we postulate that the most likely origin of subhaplogroup D1j is the region of Sierras Pampeanas, which occupies the center and part of the northwestern portion of Argentina. The extensive yet restricted geographical distribution, the relatively large internal diversity, and the absence or low incidence of D1j in other regions of South America suggest the existence of an ancient metapopulation covering the Sierras Pampeanas, being this lineage its genetic signature. Further support for a scenario of local origin for D1j in the Sierras Pampeanas stems from the fact that early derivatives from a putative ancestral lineage carrying the transitions T16311C-T152C have only been found in this region, supporting the hypothesis that it might represent an ancestral motif previous to the appearance of D1j-specific change C16242T. PMID:23114854

  15. Evolutionary and dispersal history of Eurasian house mice Mus musculus clarified by more extensive geographic sampling of mitochondrial DNA

    PubMed Central

    Suzuki, H; Nunome, M; Kinoshita, G; Aplin, K P; Vogel, P; Kryukov, A P; Jin, M-L; Han, S-H; Maryanto, I; Tsuchiya, K; Ikeda, H; Shiroishi, T; Yonekawa, H; Moriwaki, K

    2013-01-01

    We examined the sequence variation of mitochondrial DNA control region and cytochrome b gene of the house mouse (Mus musculus sensu lato) drawn from ca. 200 localities, with 286 new samples drawn primarily from previously unsampled portions of their Eurasian distribution and with the objective of further clarifying evolutionary episodes of this species before and after the onset of human-mediated long-distance dispersals. Phylogenetic analysis of the expanded data detected five equally distinct clades, with geographic ranges of northern Eurasia (musculus, MUS), India and Southeast Asia (castaneus, CAS), Nepal (unspecified, NEP), western Europe (domesticus, DOM) and Yemen (gentilulus). Our results confirm previous suggestions of Southwestern Asia as the likely place of origin of M. musculus and the region of Iran, Afghanistan, Pakistan, and northern India, specifically as the ancestral homeland of CAS. The divergence of the subspecies lineages and of internal sublineage differentiation within CAS were estimated to be 0.37–0.47 and 0.14–0.23 million years ago (mya), respectively, assuming a split of M. musculus and Mus spretus at 1.7 mya. Of the four CAS sublineages detected, only one extends to eastern parts of India, Southeast Asia, Indonesia, Philippines, South China, Northeast China, Primorye, Sakhalin and Japan, implying a dramatic range expansion of CAS out of its homeland during an evolutionary short time, perhaps associated with the spread of agricultural practices. Multiple and non-coincident eastward dispersal events of MUS sublineages to distant geographic areas, such as northern China, Russia and Korea, are inferred, with the possibility of several different routes. PMID:23820581

  16. Ancient mitochondrial genome reveals trace of prehistoric migration in the east Pamir by pastoralists.

    PubMed

    Ning, Chao; Gao, Shizhu; Deng, Boping; Zheng, Hongxiang; Wei, Dong; Lv, Haoze; Li, Hongjie; Song, Li; Wu, Yong; Zhou, Hui; Cui, Yinqiu

    2016-02-01

    The complete mitochondrial genome of one 700-year-old individual found in Tashkurgan, Xinjiang was target enriched and sequenced in order to shed light on the population history of Tashkurgan and determine the phylogenetic relationship of haplogroup U5a. The ancient sample was assigned to a subclade of haplogroup U5a2a1, which is defined by two rare and stable transversions at 16114A and 13928C. Phylogenetic analysis shows a distribution pattern for U5a2a that is indicative of an origin in the Volga-Ural region and exhibits a clear eastward geographical expansion that correlates with the pastoral culture also entering the Eurasian steppe. The haplogroup U5a2a present in the ancient Tashkurgan individual reveals prehistoric migration in the East Pamir by pastoralists. This study shows that studying an ancient mitochondrial genome is a useful approach for studying the evolutionary process and population history of Eastern Pamir. PMID:26511065

  17. Mitochondrial Genomic Analysis of Late Onset Alzheimer’s Disease Reveals Protective Haplogroups H6A1A/H6A1B: The Cache County Study on Memory in Aging

    PubMed Central

    Ridge, Perry G.; Maxwell, Taylor J.; Corcoran, Christopher D.; Norton, Maria C.; Tschanz, JoAnn T.; O’Brien, Elizabeth; Kerber, Richard A.; Cawthon, Richard M.; Munger, Ronald G.; Kauwe, John S. K.

    2012-01-01

    Background Alzheimer’s disease (AD) is the most common cause of dementia and AD risk clusters within families. Part of the familial aggregation of AD is accounted for by excess maternal vs. paternal inheritance, a pattern consistent with mitochondrial inheritance. The role of specific mitochondrial DNA (mtDNA) variants and haplogroups in AD risk is uncertain. Methodology/Principal Findings We determined the complete mitochondrial genome sequence of 1007 participants in the Cache County Study on Memory in Aging, a population-based prospective cohort study of dementia in northern Utah. AD diagnoses were made with a multi-stage protocol that included clinical examination and review by a panel of clinical experts. We used TreeScanning, a statistically robust approach based on haplotype networks, to analyze the mtDNA sequence data. Participants with major mitochondrial haplotypes H6A1A and H6A1B showed a reduced risk of AD (p = 0.017, corrected for multiple comparisons). The protective haplotypes were defined by three variants: m.3915G>A, m.4727A>G, and m.9380G>A. These three variants characterize two different major haplogroups. Together m.4727A>G and m.9380G>A define H6A1, and it has been suggested m.3915G>A defines H6A. Additional variants differentiate H6A1A and H6A1B; however, none of these variants had a significant relationship with AD case-control status. Conclusions/Significance Our findings provide evidence of a reduced risk of AD for individuals with mtDNA haplotypes H6A1A and H6A1B. These findings are the results of the largest study to date with complete mtDNA genome sequence data, yet the functional significance of the associated haplotypes remains unknown and replication in others studies is necessary. PMID:23028804

  18. The 12S rRNA A1555G mutation in the mitochondrial haplogroup D5a is responsible for maternally inherited hypertension and hearing loss in two Chinese pedigrees

    PubMed Central

    Chen, Hong; Zheng, Jing; Xue, Ling; Meng, Yanzi; Wang, Yan; Zheng, Bingjiao; Fang, Fang; Shi, Suxue; Qiu, Qiaomeng; Jiang, Pingping; Lu, Zhongqiu; Mo, Jun Qin; Lu, Jianxin; Guan, Min-Xin

    2012-01-01

    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. PMID:22317974

  19. The 12S rRNA A1555G mutation in the mitochondrial haplogroup D5a is responsible for maternally inherited hypertension and hearing loss in two Chinese pedigrees.

    PubMed

    Chen, Hong; Zheng, Jing; Xue, Ling; Meng, Yanzi; Wang, Yan; Zheng, Bingjiao; Fang, Fang; Shi, Suxue; Qiu, Qiaomeng; Jiang, Pingping; Lu, Zhongqiu; Mo, Jun Qin; Lu, Jianxin; Guan, Min-Xin

    2012-06-01

    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. PMID:22317974

  20. The mitochondrial tRNA(Gln) T4353C mutation may not be associated with essential hypertension in Han Chinese population.

    PubMed

    Meng, Xing; Pei, Hui; Lan, Chao

    2016-09-01

    We reported here the possible role of a mitochondrial tRNA mutation: T4353C in clinical expression of essential hypertension in Chinese population. The human mammalian mitochondrial tRNA database was used to analyze the conservation index of this mutation between different species. Moreover, phylogenetic analysis showed that the T4353C mutation belonged to human mitochondrial haplogroup HV, a West Eurasian haplogroup found throughout Western Asia and Eastern European but was infrequent in China. In addition, structural prediction of the T4353C mutation indicated that this transition did not alter the secondary structure of tRNA(Gln). Together, our data indicated that the T4353C mutation occurred infrequent and may not be associated with essential hypertension in Han Chinese population. PMID:25693701

  1. The genetic impact of the lake chad basin population in North Africa as documented by mitochondrial diversity and internal variation of the L3e5 haplogroup.

    PubMed

    Podgorná, Eliška; Soares, Pedro; Pereira, Luísa; Cerný, Viktor

    2013-11-01

    The presence of sub-Saharan L-type mtDNA sequences in North Africa has traditionally been explained by the recent slave trade. However, gene flow between sub-Saharan and northern African populations would also have been made possible earlier through the greening of the Sahara resulting from Early Holocene climatic improvement. In this article, we examine human dispersals across the Sahara through the analysis of the sub-Saharan mtDNA haplogroup L3e5, which is not only commonly found in the Lake Chad Basin (∼17%), but which also attains nonnegligible frequencies (∼10%) in some Northwestern African populations. Age estimates point to its origin ∼10 ka, probably directly in the Lake Chad Basin, where the clade occurs across linguistic boundaries. The virtual absence of this specific haplogroup in Daza from Northern Chad and all West African populations suggests that its migration took place elsewhere, perhaps through Northern Niger. Interestingly, independent confirmation of Early Holocene contacts between North Africa and the Lake Chad Basin have been provided by craniofacial data from Central Niger, supporting our suggestion that the Early Holocene offered a suitable climatic window for genetic exchanges between North and sub-Saharan Africa. In view of its younger founder age in North Africa, the discontinuous distribution of L3e5 was probably caused by the Middle Holocene re-expansion of the Sahara desert, disrupting the clade's original continuous spread. PMID:25069842

  2. 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.

    PubMed

    Li, Wei; Wen, Chaowei; Li, Weixing; Wang, Hailing; Guan, Xiaomin; Zhang, Wanlin; Ye, Wei; Lu, Jianxin

    2015-10-01

    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 tRNA(Gly). Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNA(Gly) significantly affected and the amount of tRNA(Gly) 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 tRNA(Gly) gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family. PMID:26134044

  3. Cryptic crested newt diversity at the Eurasian transition: the mitochondrial DNA phylogeography of Near Eastern Triturus newts.

    PubMed

    Wielstra, B; Themudo, G Espregueira; Güçlü, O; Olgun, K; Poyarkov, N A; Arntzen, J W

    2010-09-01

    Crested newts of the Triturus karelinii group occur in a phylogeographically understudied region: the Near East. Controversy surrounds the systematic position of these newts within the complete crested newt assemblage (the Triturus cristatus superspecies). We explore the situation using mitochondrial sequence data (ND2 and ND4, approximately 1.7kb) and employing different methods of phylogenetic inference (Bayesian inference and Maximum Likelihood using mixed models) and molecular dating (r8s and BEAST). The T. karelinii group is monophyletic and constitutes one of four main lineages in the T. cristatus superspecies. The separation of the T. karelinii group from the remaining crested newts around 9Ma is related to the formation of the Mid-Aegean Trench, which separated the Balkan and Anatolian landmasses. The T. karelinii group comprises three geographically structured clades (eastern, central and western). The genetic divergence shown by these clades is comparable to that among recognized crested newt species. We suggest the uplift of the Armenian Plateau to be responsible for the separation of the eastern clade around 7Ma, and the re-establishment of a marine connection between the Black Sea and the Mediterranean at the end of the Messinian Salinity Crisis to have caused the split between the central and western clade around 5.5Ma. Genetic structuring within the three clades dates to the Quaternary Ice Age (<2.59Ma) and is associated with alternating periods of isolation and reconnection caused by periodic changes in sea level and surface runoff. PMID:20435147

  4. Helena, the hidden beauty: Resolving the most common West Eurasian mtDNA control region haplotype by massively parallel sequencing an Italian population sample.

    PubMed

    Bodner, Martin; Iuvaro, Alessandra; Strobl, Christina; Nagl, Simone; Huber, Gabriela; Pelotti, Susi; Pettener, Davide; Luiselli, Donata; Parson, Walther

    2015-03-01

    The analysis of mitochondrial (mt)DNA is a powerful tool in forensic genetics when nuclear markers fail to give results or maternal relatedness is investigated. The mtDNA control region (CR) contains highly condensed variation and is therefore routinely typed. Some samples exhibit an identical haplotype in this restricted range. Thus, they convey only weak evidence in forensic queries and limited phylogenetic information. However, a CR match does not imply that also the mtDNA coding regions are identical or samples belong to the same phylogenetic lineage. This is especially the case for the most frequent West Eurasian CR haplotype 263G 315.1C 16519C, which is observed in various clades within haplogroup H and occurs at a frequency of 3-4% in many European populations. In this study, we investigated the power of massively parallel complete mtGenome sequencing in 29 Italian samples displaying the most common West Eurasian CR haplotype - and found an unexpected high diversity. Twenty-eight different haplotypes falling into 19 described sub-clades of haplogroup H were revealed in the samples with identical CR sequences. This study demonstrates the benefit of complete mtGenome sequencing for forensic applications to enforce maximum discrimination, more comprehensive heteroplasmy detection, as well as highest phylogenetic resolution. PMID:25303789

  5. Ethiopian Mitochondrial DNA Heritage: Tracking Gene Flow Across and Around the Gate of Tears

    PubMed Central

    Kivisild, Toomas; Reidla, Maere; Metspalu, Ene; Rosa, Alexandra; Brehm, Antonio; Pennarun, Erwan; Parik, Jüri; Geberhiwot, Tarekegn; Usanga, Esien; Villems, Richard

    2004-01-01

    Approximately 10 miles separate the Horn of Africa from the Arabian Peninsula at Bab-el-Mandeb (the Gate of Tears). Both historic and archaeological evidence indicate tight cultural connections, over millennia, between these two regions. High-resolution phylogenetic analysis of 270 Ethiopian and 115 Yemeni mitochondrial DNAs was performed in a worldwide context, to explore gene flow across the Red and Arabian Seas. Nine distinct subclades, including three newly defined ones, were found to characterize entirely the variation of Ethiopian and Yemeni L3 lineages. Both Ethiopians and Yemenis contain an almost-equal proportion of Eurasian-specific M and N and African-specific lineages and therefore cluster together in a multidimensional scaling plot between Near Eastern and sub-Saharan African populations. Phylogeographic identification of potential founder haplotypes revealed that approximately one-half of haplogroup L0–L5 lineages in Yemenis have close or matching counterparts in southeastern Africans, compared with a minor share in Ethiopians. Newly defined clade L6, the most frequent haplogroup in Yemenis, showed no close matches among 3,000 African samples. These results highlight the complexity of Ethiopian and Yemeni genetic heritage and are consistent with the introduction of maternal lineages into the South Arabian gene pool from different source populations of East Africa. A high proportion of Ethiopian lineages, significantly more abundant in the northeast of that country, trace their western Eurasian origin in haplogroup N through assorted gene flow at different times and involving different source populations. PMID:15457403

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

    PubMed

    Torrell, Helena; Salas, Antonio; Abasolo, Nerea; Morén, Constanza; Garrabou, Glòria; Valero, Joaquín; Alonso, Yolanda; Vilella, Elisabet; Costas, Javier; Martorell, Lourdes

    2014-10-01

    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. PMID:25132006

  7. Mitochondrial phylogeny of the Eurasian/African reed warbler complex (Acrocephalus, Aves). Disagreement between morphological and molecular evidence and cryptic divergence: A case for resurrecting Calamoherpe ambigua Brehm 1857.

    PubMed

    Olsson, Urban; Rguibi-Idrissi, Hamid; Copete, José Luis; Arroyo Matos, José Luis; Provost, Pascal; Amezian, Mohamed; Alström, Per; Jiguet, Frédéric

    2016-09-01

    A tree based on the mitochondrial cyt b gene for 278 samples from throughout the range of the Eurasian Reed Warbler Acrocephalus scirpaceus - African Reed Warbler A. baeticatus complex shows well-supported geographically structured divergence for eight distinct lineages. The phylogenetic structuring together with the clarification of priority, provided by sequence data from seven type specimens, suggests that both taxonomy and distribution boundaries are in need of revision. The Iberian and Moroccan populations form a well-supported clade, and we propose that these are treated as taxonomically distinct, under the name ambiguus (Brehm, 1857). We propose that the names scirpaceus, fuscus, avicenniae, ambiguus, minor, cinnamomeus, hallae and baeticatus are used for the well supported clades in the complex, which we recommend to treat as one polytypic species, A. scirpaceus, pending studies of gene flow and assortative mating in the contact zones. PMID:27233439

  8. Study of the T16189C variant and mitochondrial lineages in Tunisian and overall Mediterranean region.

    PubMed

    Hsouna, Sana; Ben Halim, Nizar; Lasram, Khaled; Meiloud, Ghlana; Arfa, Imen; Kerkeni, Emna; Romdhane, Lilia; Jamoussi, Henda; Bahri, Sonia; Ben Ammar, Slim; Abid, Abdelmajid; Barakat, Abdelhamid; Houmeida, Ahmed; Abdelhak, Sonia; Kefi, Rym

    2016-01-01

    The mitochondrial DNA (mtDNA) variant T16189C has been investigated in several metabolic diseases. In this study, we aimed to estimate the frequency of the T16189C variant in Tunisian and other Mediterranean populations and to evaluate the impact of this variant on the phylogeny of Mediterranean populations. Blood sample of 240 unrelated Tunisian subjects were recruited from several Tunisian localities. The hypervariable region 1 of the mtDNA were amplified and sequenced. Additional sequences (N = 4921) from Mediterranean populations were compiled from previous studies. The average frequency of T16189C variant in Tunisia (29%) is similar to that observed in North African and Near Eastern populations. Our findings showed positive correlation of the T16189C variant with Sub-Saharan and North African lineages, while a negative correlation was found with the Eurasian haplogroups, reaching its maximum with the Eurasian haplogroup H. The principal component analyses showed a high internal heterogeneity between Tunisian localities. At the Mediterranean scale, Tunisians are closer to North African (Algerian and Moroccan) and Near Eastern populations (Syrians and Palestinians) than to Europeans. PMID:25208176

  9. The Western and Eastern Roots of the Saami—the Story of Genetic “Outliers” Told by Mitochondrial DNA and Y Chromosomes

    PubMed Central

    Tambets, Kristiina; Rootsi, Siiri; Kivisild, Toomas; Help, Hela; Serk, Piia; Loogväli, Eva-Liis; Tolk, Helle-Viivi; Reidla, Maere; Metspalu, Ene; Pliss, Liana; Balanovsky, Oleg; Pshenichnov, Andrey; Balanovska, Elena; Gubina, Marina; Zhadanov, Sergey; Osipova, Ludmila; Damba, Larisa; Voevoda, Mikhail; Kutuev, Ildus; Bermisheva, Marina; Khusnutdinova, Elza; Gusar, Vladislava; Grechanina, Elena; Parik, Jüri; Pennarun, Erwan; Richard, Christelle; Chaventre, Andre; Moisan, Jean-Paul; Barać, Lovorka; Peričić, Marijana; Rudan, Pavao; Terzić, Rifat; Mikerezi, Ilia; Krumina, Astrida; Baumanis, Viesturs; Koziel, Slawomir; Rickards, Olga; De Stefano, Gian Franco; Anagnou, Nicholas; Pappa, Kalliopi I.; Michalodimitrakis, Emmanuel; Ferák, Vladimir; Füredi, Sandor; Komel, Radovan; Beckman, Lars; Villems, Richard

    2004-01-01

    The Saami are regarded as extreme genetic outliers among European populations. In this study, a high-resolution phylogenetic analysis of Saami genetic heritage was undertaken in a comprehensive context, through use of maternally inherited mitochondrial DNA (mtDNA) and paternally inherited Y-chromosomal variation. DNA variants present in the Saami were compared with those found in Europe and Siberia, through use of both new and previously published data from 445 Saami and 17,096 western Eurasian and Siberian mtDNA samples, as well as 127 Saami and 2,840 western Eurasian and Siberian Y-chromosome samples. It was shown that the “Saami motif” variant of mtDNA haplogroup U5b is present in a large area outside Scandinavia. A detailed phylogeographic analysis of one of the predominant Saami mtDNA haplogroups, U5b1b, which also includes the lineages of the “Saami motif,” was undertaken in 31 populations. The results indicate that the origin of U5b1b, as for the other predominant Saami haplogroup, V, is most likely in western, rather than eastern, Europe. Furthermore, an additional haplogroup (H1) spread among the Saami was virtually absent in 781 Samoyed and Ob-Ugric Siberians but was present in western and central European populations. The Y-chromosomal variety in the Saami is also consistent with their European ancestry. It suggests that the large genetic separation of the Saami from other Europeans is best explained by assuming that the Saami are descendants of a narrow, distinctive subset of Europeans. In particular, no evidence of a significant directional gene flow from extant aboriginal Siberian populations into the haploid gene pools of the Saami was found. PMID:15024688

  10. The mitochondrial DNA makeup of Romanians: A forensic mtDNA control region database and phylogenetic characterization.

    PubMed

    Turchi, Chiara; Stanciu, Florin; Paselli, Giorgia; Buscemi, Loredana; Parson, Walther; Tagliabracci, Adriano

    2016-09-01

    To evaluate the pattern of Romanian population from a mitochondrial perspective and to establish an appropriate mtDNA forensic database, we generated a high-quality mtDNA control region dataset from 407 Romanian subjects belonging to four major historical regions: Moldavia, Transylvania, Wallachia and Dobruja. The entire control region (CR) was analyzed by Sanger-type sequencing assays and the resulting 306 different haplotypes were classified into haplogroups according to the most updated mtDNA phylogeny. The Romanian gene pool is mainly composed of West Eurasian lineages H (31.7%), U (12.8%), J (10.8%), R (10.1%), T (9.1%), N (8.1%), HV (5.4%),K (3.7%), HV0 (4.2%), with exceptions of East Asian haplogroup M (3.4%) and African haplogroup L (0.7%). The pattern of mtDNA variation observed in this study indicates that the mitochondrial DNA pool is geographically homogeneous across Romania and that the haplogroup composition reveals signals of admixture of populations of different origin. The PCA scatterplot supported this scenario, with Romania located in southeastern Europe area, close to Bulgaria and Hungary, and as a borderland with respect to east Mediterranean and other eastern European countries. High haplotype diversity (0.993) and nucleotide diversity indices (0.00838±0.00426), together with low random match probability (0.0087) suggest the usefulness of this control region dataset as a forensic database in routine forensic mtDNA analysis and in the investigation of maternal genetic lineages in the Romanian population. PMID:27414754

  11. Origin and Diffusion of mtDNA Haplogroup X

    PubMed Central

    Reidla, Maere; Kivisild, Toomas; Metspalu, Ene; Kaldma, Katrin; Tambets, Kristiina; Tolk, Helle-Viivi; Parik, Jüri; Loogväli, Eva-Liis; Derenko, Miroslava; Malyarchuk, Boris; Bermisheva, Marina; Zhadanov, Sergey; Pennarun, Erwan; Gubina, Marina; Golubenko, Maria; Damba, Larisa; Fedorova, Sardana; Gusar, Vladislava; Grechanina, Elena; Mikerezi, Ilia; Moisan, Jean-Paul; Chaventré, André; Khusnutdinova, Elsa; Osipova, Ludmila; Stepanov, Vadim; Voevoda, Mikhail; Achilli, Alessandro; Rengo, Chiara; Rickards, Olga; De Stefano, Gian Franco; Papiha, Surinder; Beckman, Lars; Janicijevic, Branka; Rudan, Pavao; Anagnou, Nicholas; Michalodimitrakis, Emmanuel; Koziel, Slawomir; Usanga, Esien; Geberhiwot, Tarekegn; Herrnstadt, Corinna; Howell, Neil; Torroni, Antonio; Villems, Richard

    2003-01-01

    A maximum parsimony tree of 21 complete mitochondrial DNA (mtDNA) sequences belonging to haplogroup X and the survey of the haplogroup-associated polymorphisms in 13,589 mtDNAs from Eurasia and Africa revealed that haplogroup X is subdivided into two major branches, here defined as “X1” and “X2.” The first is restricted to the populations of North and East Africa and the Near East, whereas X2 encompasses all X mtDNAs from Europe, western and Central Asia, Siberia, and the great majority of the Near East, as well as some North African samples. Subhaplogroup X1 diversity indicates an early coalescence time, whereas X2 has apparently undergone a more recent population expansion in Eurasia, most likely around or after the last glacial maximum. It is notable that X2 includes the two complete Native American X sequences that constitute the distinctive X2a clade, a clade that lacks close relatives in the entire Old World, including Siberia. The position of X2a in the phylogenetic tree suggests an early split from the other X2 clades, likely at the very beginning of their expansion and spread from the Near East. PMID:14574647

  12. A study of genetic polymorphisms in mitochondrial DNA hypervariable regions I and II of the five major ethnic groups and Vedda population in Sri Lanka.

    PubMed

    Ranasinghe, Ruwandi; Tennekoon, Kamani H; Karunanayake, Eric H; Lembring, Maria; Allen, Marie

    2015-11-01

    Diversity of the hypervariable regions (HV) I and II of the mitochondrial genome was studied in maternally unrelated Sri Lankans (N=202) from six ethnic groups (i.e.: Sinhalese, Sri Lankan Tamil, Muslim, Malay, Indian Tamil and Vedda). DNA was extracted from blood and buccal swabs and HVI and HVII regions were PCR amplified and sequenced. Resulting sequences were aligned and edited between 16024-16365 and 73-340 regions and compared with revised Cambridge reference sequences (rCRS). One hundred and thirty-five unique haplotypes and 22 shared haplotypes were observed. A total of 145 polymorphic sites and 158 polymorphisms were observed. Hypervariable region I showed a higher polymorphic variation than hypervariable region II. Nucleotide diversities were quite low and similar for all ethnicities apart from a slightly higher value for Indian Tamils and a much lower value for the Vedda population compared to the other groups. When the total population was considered South Asian (Indian) haplogroups were predominant, but there were differences in the distribution of phylo-geographical haplogroups between ethnic groups. Sinhalese, Sri Lankan Tamil and Vedda populations had a considerable presence of West Eurasian haplogroups. About 2/3rd of the Vedda population comprised of macro-haplogroup N or its subclades R and U, whereas macro-haplogroup M was predominant in all other populations. The Vedda population clustered separately from other groups and Sri Lankan Tamils showed a closer genetic affiliation to Sinhalese than to Indian Tamils. Thus this study provides useful information for forensic analysis and anthropological studies of Sri Lankans. PMID:26065620

  13. Comparative mitochondrial genetics of North American and Eurasian mergansers with an emphasis on the endangered scaly-sided merganser (Mergus squamatus)

    USGS Publications Warehouse

    Solovyeva, Diana V.; Pearce, John M.

    2011-01-01

    The scaly-sided merganser, Mergus squamatus, is considered one of the most threatened sea duck species in the Palearctic with limited breeding and wintering distribution in China and Russia. To provide information for future conservation efforts, we sequenced a portion of the mitochondrial (mt) DNA control region in four species of mergansers and three additional sea duck taxa to characterize the evolutionary history of the scaly-sided merganser, infer population trends that may have led to its limited geographic distribution, and to compare indices of genetic diversity among species of mergansers. Scaly-sided mergansers exhibit substantially lower levels of mtDNA genetic diversity (h = 0.292, π= 0.0007) than other closely related sea ducks and many other avian taxa. The four haplotypes observed differed by a single base pair suggesting that the species has not experienced a recent population decline but has instead been at a low population level for some time. A phylogenetic analysis placed the scaly-sided merganser basal to North American and European forms of the common merganser, M. merganser. Our inclusion of a small number of male samples doubled the number of mtDNA haplotypes observed, suggesting that additional genetic variation likely exists within the global population if there is immigration of males from unsampled breeding areas.

  14. Comparative mitochondrial genetics of North American and Eurasian mergansers with an emphasis on the endangered scaly-sided merganser (Mergus squamatus)

    USGS Publications Warehouse

    Solovyeva, D.V.; Pearce, J.M.

    2011-01-01

    The scaly-sided merganser, Mergus squamatus, is considered one of the most threatened sea duck species in the Palearctic with limited breeding and wintering distribution in China and Russia. To provide information for future conservation efforts, we sequenced a portion of the mitochondrial (mt) DNA control region in four species of mergansers and three additional sea duck taxa to characterize the evolutionary history of the scaly-sided merganser, infer population trends that may have led to its limited geographic distribution, and to compare indices of genetic diversity among species of mergansers. Scaly-sided mergansers exhibit substantially lower levels of mtDNA genetic diversity (h = 0.292, ?? = 0.0007) than other closely related sea ducks and many other avian taxa. The four haplotypes observed differed by a single base pair suggesting that the species has not experienced a recent population decline but has instead been at a low population level for some time. A phylogenetic analysis placed the scaly-sided merganser basal to North American and European forms of the common merganser, M. merganser. Our inclusion of a small number of male samples doubled the number of mtDNA haplotypes observed, suggesting that additional genetic variation likely exists within the global population if there is immigration of males from unsampled breeding areas. ?? 2011 US Government.

  15. Tracing the Austronesian footprint in Mainland Southeast Asia: a perspective from mitochondrial DNA.

    PubMed

    Peng, Min-Sheng; Quang, Huy Ho; Dang, Khoa Pham; Trieu, An Vu; Wang, Hua-Wei; Yao, Yong-Gang; Kong, Qing-Peng; Zhang, Ya-Ping

    2010-10-01

    As the relic of the ancient Champa Kingdom, the Cham people represent the major Austronesian speakers in Mainland Southeast Asia (MSEA) and their origin is evidently associated with the Austronesian diffusion in MSEA. Hitherto, hypotheses stemming mainly from linguistic and cultural viewpoints on the origin of the Cham people remain a welter of controversies. Among the points of dissension is the muddled issue of whether the Cham people arose from demic or cultural diffusion from the Austronesians. Addressing this issue also helps elucidate the dispersal mode of the Austronesian language. In the present study, we have analyzed mitochondrial DNA (mtDNA) control-region and coding-region sequence variations in 168 Cham and 139 Kinh individuals from Vietnam. Around 77% and 95% matrilineal components in the Chams and the Kinhs, respectively, could be assigned into the defined mtDNA haplogroups. Additionally, three common East Eurasian haplogroups B, R9, and M7 account for the majority (>60%) of maternal components in both populations. Entire sequencing of 20 representative mtDNAs selected from the thus far unclassified lineages, together with four new mtDNA genome sequences from Thailand, led to the identification of one new haplogroup M77 and helped to re-evaluate several haplogroups determined previously. Comparing the Chams with other Southeast Asian populations reveals that the Chams had a closer affinity with the Mon-Khmer populations in MSEA than with the Austronesian populations from Island Southeast Asia (ISEA). Further analyses failed to detect the potential homelands of the Chams in ISEA. Therefore, our results suggested that the origin of the Cham was likely a process of assimilation of massive local Mon-Khmer populations accompanied with language shift, thus indicating that the Austronesian diffusion in MSEA was mainly mediated by cultural diffusion, at least from the matrilineal genetic perspective, an observation in agreement with the hypothesis of the

  16. Mitochondrial lineage M1 traces an early human backflow to Africa

    PubMed Central

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-01-01

    Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance. PMID:17620140

  17. Pan-American mDNA haplogroups in Chilean patients with Leber’s hereditary optic neuropathy

    PubMed Central

    Romero, Pablo; Fernández, Verónica; Slabaugh, Mark; Seleme, Nicolás; Reyes, Nury; Gallardo, Patricia; Herrera, Luisa; Peña, Luis; Pezo, Patricio; Moraga, Mauricio

    2014-01-01

    Purpose The clinical impact of mDNA mutations on the development of Leber hereditary optic neuropathy (LHON) may be modulated by mitochondrial haplogroups, which vary across populations. The aim of this research was to determine the clinical spectrum and molecular characteristics, including the haplogroup, of 15 South American families with LHON. Methods This study was a prospective, observational study conducted between March 2006 and August 2012. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular studies were conducted at the Biomedical Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were identified with molecular analysis after initial neuroophthalmic examination at different centers throughout Chile. Clinical features of patients with LHON and maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or m.14484T>C) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplogroups were determined with direct sequencing of two hypervariable regions (HV1 and HV2) and compared with reference sequences. Results The m.11778G>A mutation was found in 59 subjects (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had Amerindian haplogroups: One family had the A2 haplogroup, four families had the B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g haplogroup. Conclusions In this limited sample size, the Amerindian haplogroup A2 was associated with delayed onset of disease in this population. Patients with haplogroup C retained better vision

  18. Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

    PubMed Central

    Kushniarevich, Alena; Sivitskaya, Larysa; Danilenko, Nina; Novogrodskii, Tadeush; Tsybovsky, Iosif; Kiseleva, Anna; Kotova, Svetlana; Chaubey, Gyaneshwer; Metspalu, Ene; Sahakyan, Hovhannes; Bahmanimehr, Ardeshir; Reidla, Maere; Rootsi, Siiri; Parik, Jüri; Reisberg, Tuuli; Achilli, Alessandro; Hooshiar Kashani, Baharak; Gandini, Francesca; Olivieri, Anna; Behar, Doron M.; Torroni, Antonio; Davydenko, Oleg; Villems, Richard

    2013-01-01

    Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively. PMID:23785503

  19. Mitochondrial DNA studies show asymmetrical Amerindian admixture in Afro-Colombian and Mestizo populations.

    PubMed

    Rodas, Clemencia; Gelvez, Nancy; Keyeux, Genoveva

    2003-02-01

    The origin of the African populations that arrived on the Colombian coasts at the time of the Spanish conquest and their subsequent settlement throughout the country and interaction with Amerindian and Spanish populations are features that can be analyzed through the study of mitochondrial DNA (mtDNA) markers. For this purpose, the present study investigates the admixture between these populations by analyzing the markers defining the main (A, B, C, D) and minor (X) founder haplogroups in Native Americans, the principal African haplogroup (L), and additional generic markers present in Caucasian (I, J, K, H, T, U, V, W) and minor African lineages (L3). As part of an interdisciplinary research program (the Expedición Humana, furthered by the Universidad Javeriana and directed by J.E. Bernal V.), 159 Afro-Colombians from five populations in which they are the majority and 91 urban Mestizos were studied. No Amerindian haplogroups (A-D, X) were detected in 81% of the Afro-Colombians. In those samples with Amerindian lineages (average 18.8%, with a range from 10% to 43%), haplogroup B predominated. When analyzed for the presence of African haplotypes, Afro-Colombians showed an overall frequency of 35.8% for haplogroup L mtDNAs, although with broad differences between populations. A few Afro-Colombian samples (1.9%) had mutations that have not been described before, and might therefore be considered as previously unsampled African variants or as new mutations arising in the American continent. Conversely, in Mestizos less than 22% of their mtDNAs belonged to non-Amerindian lineages, of which most were likely to be West Eurasian in origin. Haplogroup L mtDNAs were found in only one Mestizo (1.1%), indicating that, if present, admixture with African women would bring in other, rarer African lineages. On the other hand, in an accompanying paper (Keyeux et al. 2002) we have shown that Amerindians from Colombia have experienced little or no matrilineal admixture with

  20. Comparison of mtDNA haplogroups in Hungarians with four other European populations: a small incidence of descents with Asian origin.

    PubMed

    Nadasi, Edit; Gyurus, P; Czakó, Márta; Bene, Judit; Kosztolányi, Sz; Fazekas, Sz; Dömösi, P; Melegh, B

    2007-06-01

    Hungarians are unique among the other European populations because according to history, the ancient Magyars had come from the eastern side of the Ural Mountains and settled down in the Carpathian basin in the 9th century AD. Since variations in the human mitochondrial genome (mtDNA) are routinely used to infer the histories of different populations, we examined the distribution of restriction fragment length polymorphism (RFLP) sites of the mtDNA in apparently healthy, unrelated Hungarian subjects in order to collect data on the genetic origin of the Hungarian population. Among the 55 samples analyzed, the large majority belonged to haplogroups common in other European populations, however, three samples fulfilled the requirements of haplogroup M. Since haplogroup M is classified as a haplogroup characteristic mainly for Asian populations, the presence of haplogroup M found in approximately 5% of the total suggests that an Asian matrilineal ancestry, even if in a small incidence, can be detected among modern Hungarians. PMID:17585514

  1. Severity of cardiomyopathy associated with adenine nucleotide translocator-1 deficiency correlates with mtDNA haplogroup.

    PubMed

    Strauss, Kevin A; DuBiner, Lauren; Simon, Mariella; Zaragoza, Michael; Sengupta, Partho P; Li, Peng; Narula, Navneet; Dreike, Sandra; Platt, Julia; Procaccio, Vincent; Ortiz-González, Xilma R; Puffenberger, Erik G; Kelley, Richard I; Morton, D Holmes; Narula, Jagat; Wallace, Douglas C

    2013-02-26

    Mutations of both nuclear and mitochondrial DNA (mtDNA)-encoded mitochondrial proteins can cause cardiomyopathy associated with mitochondrial dysfunction. Hence, the cardiac phenotype of nuclear DNA mitochondrial mutations might be modulated by mtDNA variation. We studied a 13-generation Mennonite pedigree with autosomal recessive myopathy and cardiomyopathy due to an SLC25A4 frameshift null mutation (c.523delC, p.Q175RfsX38), which codes for the heart-muscle isoform of the adenine nucleotide translocator-1. Ten homozygous null (adenine nucleotide translocator-1(-/-)) patients monitored over a median of 6 years had a phenotype of progressive myocardial thickening, hyperalaninemia, lactic acidosis, exercise intolerance, and persistent adrenergic activation. Electrocardiography and echocardiography with velocity vector imaging revealed abnormal contractile mechanics, myocardial repolarization abnormalities, and impaired left ventricular relaxation. End-stage heart disease was characterized by massive, symmetric, concentric cardiac hypertrophy; widespread cardiomyocyte degeneration; overabundant and structurally abnormal mitochondria; extensive subendocardial interstitial fibrosis; and marked hypertrophy of arteriolar smooth muscle. Substantial variability in the progression and severity of heart disease segregated with maternal lineage, and sequencing of mtDNA from five maternal lineages revealed two major European haplogroups, U and H. Patients with the haplogroup U mtDNAs had more rapid and severe cardiomyopathy than those with haplogroup H. PMID:23401503

  2. mtDNA analysis of 174 Eurasian populations using a new iterative rank correlation method.

    PubMed

    Juhász, Zoltán; Fehér, Tibor; Németh, Endre; Pamjav, Horolma

    2016-02-01

    In this study, we analyse 27-dimensional mtDNA haplogroup distributions of 174 Eurasian, North-African and American populations, including numerous ancient data as well. The main contribution of this work was the description of the haplogroup distribution of recent and ancient populations as compounds of certain hypothetic ancient core populations immediately or indirectly determining the migration processes in Eurasia for a long time. To identify these core populations, we developed a new iterative algorithm determining clusters of the 27 mtDNA haplogroups studied having strong rank correlation among each other within a definite subset of the populations. Based on this study, the current Eurasian populations can be considered as compounds of three early core populations regarding to maternal lineages. We wanted to show that a simultaneous analysis of ancient and recent data using a new iterative rank correlation algorithm and the weighted SOC learning technique may reveal the most important and deterministic migration processes in the past. This technique allowed us to determine geographically, historically and linguistically well-interpretable clusters of our dataset having a very specific, hardly classifiable structure. The method was validated using a 2-dimensional stepping stone model. PMID:26142878

  3. Y-chromosome and mitochondrial DNA studies on the population structure of the Christmas Island community.

    PubMed

    Wise, Cheryl A; Sullivan, Sheena G; Black, Michael L; Erber, Wendy N; Bittles, Alan H

    2005-11-01

    Christmas Island is a remote Australian territory located close to the main Indonesian island of Java. Y-chromosome and mitochondrial DNA (mtDNA) markers were used to investigate the genetic structure of the population, which comprises communities of mixed ethnic origin. Analysis of 12 Y-chromosome biallelic polymorphisms revealed a high level of gene diversity and haplotype frequencies that were consistent with source populations in southern China and Southeast Asia. mtDNA hypervariable segment I (HVS-I) sequences displayed high levels of haplotype diversity and nucleotide diversity that were comparable to various Asian populations. Genetic distances revealed extremely low mtDNA differentiation among Christmas Islanders and Asian populations. This was supported by the relatively high proportion of sequence types shared among these populations. The most common mtDNA haplogroups were M* and B, followed by D and F, which are prevalent in East/Southeast Asia. Christmas Islanders of European descent were characterized by the Eurasian haplogroup R*, and a limited degree of admixture was observed. In general, analysis of the genetic data indicated population affinities to southern Chinese (in particular from the Yunnan Province) and Southeast Asia (Thailand, Malaysia, and Cambodia), which was consistent with historical records of settlement. The combined use of these different marker systems provides a useful and appropriate model for the study of contemporary populations derived from different ethnic origins. PMID:15864813

  4. Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region

    PubMed Central

    2014-01-01

    Background The archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region. Results The mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population. Conclusions The maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to

  5. Introducing the Algerian Mitochondrial DNA and Y-Chromosome Profiles into the North African Landscape

    PubMed Central

    Bekada, Asmahan; Fregel, Rosa; Cabrera, Vicente M.; Larruga, José M.; Pestano, José; Benhamamouch, Soraya; González, Ana M.

    2013-01-01

    North Africa is considered a distinct geographic and ethnic entity within Africa. Although modern humans originated in this Continent, studies of mitochondrial DNA (mtDNA) and Y-chromosome genealogical markers provide evidence that the North African gene pool has been shaped by the back-migration of several Eurasian lineages in Paleolithic and Neolithic times. More recent influences from sub-Saharan Africa and Mediterranean Europe are also evident. The presence of East-West and North-South haplogroup frequency gradients strongly reinforces the genetic complexity of this region. However, this genetic scenario is beset with a notable gap, which is the lack of consistent information for Algeria, the largest country in the Maghreb. To fill this gap, we analyzed a sample of 240 unrelated subjects from a northwest Algeria cosmopolitan population using mtDNA sequences and Y-chromosome biallelic polymorphisms, focusing on the fine dissection of haplogroups E and R, which are the most prevalent in North Africa and Europe respectively. The Eurasian component in Algeria reached 80% for mtDNA and 90% for Y-chromosome. However, within them, the North African genetic component for mtDNA (U6 and M1; 20%) is significantly smaller than the paternal (E-M81 and E-V65; 70%). The unexpected presence of the European-derived Y-chromosome lineages R-M412, R-S116, R-U152 and R-M529 in Algeria and the rest of the Maghreb could be the counterparts of the mtDNA H1, H3 and V subgroups, pointing to direct maritime contacts between the European and North African sides of the western Mediterranean. Female influx of sub-Saharan Africans into Algeria (20%) is also significantly greater than the male (10%). In spite of these sexual asymmetries, the Algerian uniparental profiles faithfully correlate between each other and with the geography. PMID:23431392

  6. [Mitochondrial DNA polymorphism in populations of aboriginal residents of the Far East].

    PubMed

    Gubina, M A; Girgol'kau, L A; Babenko, V N; Damba, L D; Maksimov, V N; Voevoda, M I

    2013-07-01

    An analysis of mtDNA polymorphism in eight populations of aboriginal residents (N = 519) of the Far East has been performed. The majority of haplogroups revealed in the examined groups were of East Eurasian origin. Haplogroup D was revealed in seven populations and its frequency varied from 2.8% in Koryaks to 28.3 and 28.9% in Nanaians and Evenks, respectively. Chukchi and Koryak populations, which belong to the same language family, exhibited haplogroup G, which has the same motive and indicates the genetic kinship of both populations. The presence of East Eurasian haplogroups A and D with a strong predominance of haplogroup A in Chukchi indicates the closer relationship of this population both with Asian and Canadian Eskimos and northern Atapasks on the other side of Bering Strait. The high level of genetic variability was revealed in populations belonging to the Tungus-Manjur group. The high frequency of east Eurasian haplogroups in Nanaians could result from close historical associations with Siberian Evenks. PMID:24450156

  7. mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

    SciTech Connect

    Wang Chengye; Kong Qingpeng; Yao Yonggang . E-mail: ygyaozh@yahoo.com; Zhang Yaping

    2006-09-22

    Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL.

  8. The mitochondrial landscape of African Americans: An examination of more than 2500 control region haplotypes from 22 U.S. locations.

    PubMed

    Scheible, M; Just, R; Sturk-Andreaggi, K; Saunier, J; Parson, W; Parsons, T; Coble, M; Irwin, J

    2016-05-01

    The mitochondrial DNA (mtDNA) control region (16024-576) was Sanger-sequenced for a total of 2563 self-identified African Americans, using automated processing techniques and data review standards exceeding guidelines for forensic applications. Genetic diversity ranged from 0.9952 to 0.9998 in 22 population samples from 20 different states. Haplogroups of African ancestry, found in 82.48% of individuals overall, were most concentrated in the Southeast U.S. and decreased to the north and west. West African and West Central African haplotypes were well-represented in the population samples, especially in the southern U.S. states, while East African haplogroups were observed in low-frequency clusters in a handful of locations across the country. East Asian, Native American, and West Eurasian admixture was present in 3.16%, 2.93%, and 11.43% of samples, respectively. While some geographic substructure was detected across the population samples as clines in admixture frequencies, 20 of the 22 population samples were found to be statistically indistinguishable by pairwise comparisons and AMOVA calculations. Datasets from Hawaii and Idaho, however, were clear outliers. Overall, these more than 2500 control region sequences represent the most comprehensive regional sampling of African American mtDNA diversity to date, and are suitable for use in a forensic mtDNA database. The population data are made available via EMPOP (www.empop.org) and GenBank. PMID:26919661

  9. The Role of the Mitochondrial Genome in Ageing and Carcinogenesis

    PubMed Central

    Czarnecka, Anna M.; Bartnik, Ewa

    2011-01-01

    Mitochondrial DNA mutations and polymorphisms have been the focus of intensive investigations for well over a decade in an attempt to understand how they affect fundamental processes such as cancer and aging. Initial interest in mutations occurring in mitochondrial DNA of cancer cells diminished when most were found to be the same mutations which occurred during the evolution of human mitochondrial haplogroups. However, increasingly correlations are being found between various mitochondrial haplogroups and susceptibility to cancer or diseases in some cases and successful aging in others. PMID:21403887

  10. MtDNA Haplogroup A10 Lineages in Bronze Age Samples Suggest That Ancient Autochthonous Human Groups Contributed to the Specificity of the Indigenous West Siberian Population

    PubMed Central

    Pilipenko, Aleksandr S.; Trapezov, Rostislav O.; Zhuravlev, Anton A.; Molodin, Vyacheslav I.; Romaschenko, Aida G.

    2015-01-01

    Background The craniometric specificity of the indigenous West Siberian human populations cannot be completely explained by the genetic interactions of the western and eastern Eurasian groups recorded in the archaeology of the area from the beginning of the 2nd millennium BC. Anthropologists have proposed another probable explanation: contribution to the genetic structure of West Siberian indigenous populations by ancient human groups, which separated from western and eastern Eurasian populations before the final formation of their phenotypic and genetic features and evolved independently in the region over a long period of time. This hypothesis remains untested. From the genetic point of view, it could be confirmed by the presence in the gene pool of indigenous populations of autochthonous components that evolved in the region over long time periods. The detection of such components, particularly in the mtDNA gene pool, is crucial for further clarification of early regional genetic history. Results and Conclusion We present the results of analysis of mtDNA samples (n = 10) belonging to the A10 haplogroup, from Bronze Age populations of West Siberian forest-steppe (V—I millennium BC), that were identified in a screening study of a large diachronic sample (n = 96). A10 lineages, which are very rare in modern Eurasian populations, were found in all the Bronze Age groups under study. Data on the A10 lineages’ phylogeny and phylogeography in ancient West Siberian and modern Eurasian populations suggest that A10 haplogroup underwent a long-term evolution in West Siberia or arose there autochthonously; thus, the presence of A10 lineages indicates the possible contribution of early autochthonous human groups to the genetic specificity of modern populations, in addition to contributions of later interactions of western and eastern Eurasian populations. PMID:25950581

  11. Mitochondrial and Y-chromosomal profile of the Kazakh population from East Kazakhstan

    PubMed Central

    Tarlykov, Pavel V.; Zholdybayeva, Elena V.; Akilzhanova, Ainur R.; Nurkina, Zhannur M.; Sabitov, Zhaxylyk M.; Rakhypbekov, Tolebay K.; Ramanculov, Erlan M.

    2013-01-01

    Aim To study the genetic relationship of Kazakhs from East Kazakhstan to other Eurasian populations by examining paternal and maternal DNA lineages. Methods Whole blood samples were collected in 2010 from 160 unrelated healthy Kazakhs residing in East Kazakhstan. Genomic DNA was extracted with Wizard® genomic DNA Purification Kit. Nucleotide sequence of hypervariable segment I of mitochondrial DNA (mtDNA) was determined and analyzed. Seventeen Y-short tandem repeat (STR) loci were studied in 67 samples with the AmpFiSTR Y-filer PCR Amplification Kit. In addition, mtDNA data for 2701 individuals and Y-STR data for 677 individuals were retrieved from the literature for comparison. Results There was a high degree of genetic differentiation on the level of mitochondrial DNA. The majority of maternal lineages belonged to haplogroups common in Central Asia. In contrast, Y-STR data showed very low genetic diversity, with the relative frequency of the predominant haplotype of 0.612. Conclusion The results revealed different migration patterns in the population sample, showing there had been more migration among women. mtDNA genetic diversity in this population was equivalent to that in other Central Asian populations. Genetic evidence suggests the existence of a single paternal founder lineage in the population of East Kazakhstan, which is consistent with verbal genealogical data of the local tribes. PMID:23444242

  12. Identification of Polynesian mtDNA haplogroups in remains of Botocudo Amerindians from Brazil

    PubMed Central

    Gonçalves, Vanessa Faria; Stenderup, Jesper; Rodrigues-Carvalho, Cláudia; Silva, Hilton P.; Gonçalves-Dornelas, Higgor; Líryo, Andersen; Kivisild, Toomas; Malaspinas, Anna-Sapfo; Campos, Paula F.; Rasmussen, Morten; Willerslev, Eske; Pena, Sergio Danilo J.

    2013-01-01

    There is a consensus that modern humans arrived in the Americas 15,000–20,000 y ago during the Late Pleistocene, most probably from northeast Asia through Beringia. However, there is still debate about the time of entry and number of migratory waves, including apparent inconsistencies between genetic and morphological data on Paleoamericans. Here we report the identification of mitochondrial sequences belonging to haplogroups characteristic of Polynesians in DNA extracted from ancient skulls of the now extinct Botocudo Indians from Brazil. The identification of these two Polynesian haplogroups was confirmed in independent replications in Brazil and Denmark, ensuring reliability of the data. Parallel analysis of 12 other Botocudo individuals yielded only the well-known Amerindian mtDNA haplogroup C1. Potential scenarios to try to help understand these results are presented and discussed. The findings of this study may be relevant for the understanding of the pre-Columbian and/or post-Columbian peopling of the Americas. PMID:23576724

  13. Mitochondrial and Y-chromosome diversity of the Tharus (Nepal): a reservoir of genetic variation

    PubMed Central

    Fornarino, Simona; Pala, Maria; Battaglia, Vincenza; Maranta, Ramona; Achilli, Alessandro; Modiano, Guido; Torroni, Antonio; Semino, Ornella; Santachiara-Benerecetti, Silvana A

    2009-01-01

    Background Central Asia and the Indian subcontinent represent an area considered as a source and a reservoir for human genetic diversity, with many markers taking root here, most of which are the ancestral state of eastern and western haplogroups, while others are local. Between these two regions, Terai (Nepal) is a pivotal passageway allowing, in different times, multiple population interactions, although because of its highly malarial environment, it was scarcely inhabited until a few decades ago, when malaria was eradicated. One of the oldest and the largest indigenous people of Terai is represented by the malaria resistant Tharus, whose gene pool could still retain traces of ancient complex interactions. Until now, however, investigations on their genetic structure have been scarce mainly identifying East Asian signatures. Results High-resolution analyses of mitochondrial-DNA (including 34 complete sequences) and Y-chromosome (67 SNPs and 12 STRs) variations carried out in 173 Tharus (two groups from Central and one from Eastern Terai), and 104 Indians (Hindus from Terai and New Delhi and tribals from Andhra Pradesh) allowed the identification of three principal components: East Asian, West Eurasian and Indian, the last including both local and inter-regional sub-components, at least for the Y chromosome. Conclusion Although remarkable quantitative and qualitative differences appear among the various population groups and also between sexes within the same group, many mitochondrial-DNA and Y-chromosome lineages are shared or derived from ancient Indian haplogroups, thus revealing a deep shared ancestry between Tharus and Indians. Interestingly, the local Y-chromosome Indian component observed in the Andhra-Pradesh tribals is present in all Tharu groups, whereas the inter-regional component strongly prevails in the two Hindu samples and other Nepalese populations. The complete sequencing of mtDNAs from unresolved haplogroups also provided informative markers

  14. Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER.

    PubMed

    Holzinger, Emily R; Hulgan, Todd; Ellis, Ronald J; Samuels, David C; Ritchie, Marylyn D; Haas, David W; Kallianpur, Asha R; Bloss, Cinnamon S; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina M; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Franklin, Donald R; Rosario, Debralee; Selph, Doug; Letendre, Scott; Grant, Igor

    2012-12-01

    HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CNS HIV Antiretroviral Therapy Effects Research (CHARTER). CHARTER is a USA-based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ≥1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups, and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G [odds ratio (95 % confidence interval) = 0.27 (0.11-0.65); p = 0.004] and T489C [odds ratio (95 % confidence interval) = 0.41 (0.21-0.80); p = 0.009]. These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups were associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups [odds ratio (95 % confidence interval) = 0.29 (0.12-0.71); p = 0.007 and odds ratio (95 % confidence interval) = 0.42 (0.18-1.0); p = 0.05, respectively]. In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy

  15. Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau

    PubMed Central

    Zhao, Mian; Kong, Qing-Peng; Wang, Hua-Wei; Peng, Min-Sheng; Xie, Xiao-Dong; Wang, Wen-Zhi; Jiayang; Duan, Jian-Guo; Cai, Ming-Cui; Zhao, Shi-Neng; Cidanpingcuo; Tu, Yuan-Quan; Wu, Shi-Fang; Yao, Yong-Gang; Bandelt, Hans-Jürgen; Zhang, Ya-Ping

    2009-01-01

    Due to its numerous environmental extremes, the Tibetan Plateau—the world's highest plateau—is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics. PMID:19955425

  16. Physical characteristics of Eurasian winter temperature variability

    NASA Astrophysics Data System (ADS)

    Kim, Kwang-Yul; Son, Seok-Woo

    2016-04-01

    Despite the on-going global warming, recent winters in Eurasian mid-latitudes were much colder than average. In an attempt to better understand the physical characteristics for cold Eurasian winters, major sources of variability in surface air temperature (SAT) are investigated based on cyclostationary EOF analysis. The two leading modes of SAT variability represent the effect of Arctic amplification (AA) and the Arctic oscillation (AO), respectively. These two modes are distinct in terms of the physical characteristics, including surface energy fluxes and tropospheric circulations, and result in significantly different winter SAT patterns over the Eurasian continent. The AA-related SAT anomalies are dipolar with warm Arctic, centered at the Barents–Kara Seas, and cold East Asia. In contrast, the negative AO-related SAT anomalies are characterized by widespread cold anomalies in Northern Eurasia. Relative importance of the AA and the negative AO contributions to cold Eurasian winters is sensitive to the region of interest.

  17. HAPLOFIND: a new method for high-throughput mtDNA haplogroup assignment.

    PubMed

    Vianello, Dario; Sevini, Federica; Castellani, Gastone; Lomartire, Laura; Capri, Miriam; Franceschi, Claudio

    2013-09-01

    Deep sequencing technologies are completely revolutionizing the approach to DNA analysis. Mitochondrial DNA (mtDNA) studies entered in the "postgenomic era": the burst in sequenced samples observed in nuclear genomics is expected also in mitochondria, a trend that can already be detected checking complete mtDNA sequences database submission rate. Tools for the analysis of these data are available, but they fail in throughput or in easiness of use. We present here a new pipeline based on previous algorithms, inherited from the "nuclear genomic toolbox," combined with a newly developed algorithm capable of efficiently and easily classify new mtDNA sequences according to PhyloTree nomenclature. Detected mutations are also annotated using data collected from publicly available databases. Thanks to the analysis of all freely available sequences with known haplogroup obtained from GenBank, we were able to produce a PhyloTree-based weighted tree, taking into account each haplogroup pattern conservation. The combination of a highly efficient aligner, coupled with our algorithm and massive usage of asynchronous parallel processing, allowed us to build a high-throughput pipeline for the analysis of mtDNA sequences that can be quickly updated to follow the ever-changing nomenclature. HaploFind is freely accessible at the following Web address: https://haplofind.unibo.it. PMID:23696374

  18. Increased expression of ApoE and protection from amyloid-beta toxicity in transmitochondrial cybrids with haplogroup K mtDNA.

    PubMed

    Thaker, Kunal; Chwa, Marilyn; Atilano, Shari R; Coskun, Pinar; Cáceres-Del-Carpio, Javier; Udar, Nitin; Boyer, David S; Jazwinski, S Michal; Miceli, Michael V; Nesburn, Anthony B; Kuppermann, Baruch D; Kenney, M Cristina

    2016-09-01

    Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNP) patterns, represent populations of diverse geographic origins and have been associated with increased risk or protection of many diseases. The H haplogroup is the most common European haplogroup while the K haplogroup is highly associated with the Ashkenazi Jewish population. Transmitochondrial cybrids (cell lines with identical nuclei, but mtDNA from either H (n=8) or K (n=8) subjects) were analyzed by the Seahorse flux analyzer, quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC). Cybrids were treated with amyloid-β peptides and cell viabilities were measured. Other cybrids were demethylated with 5-aza-2'-deoxycytidine (5-aza-dC) and expression levels for APOE and NFkB2 were measured. Results show K cybrids have (a) significantly lower mtDNA copy numbers, (b) higher expression levels for MT-DNA encoded genes critical for oxidative phosphorylation, (c) lower Spare Respiratory Capacity, (d) increased expression of inhibitors of the complement pathway and important inflammasome-related genes; and (e) significantly higher levels of APOE transcription that were independent of methylation status. After exposure to amyloid-β1-42 peptides (active form), H haplogroup cybrids demonstrated decreased cell viability compared to those treated with amyloid-β42-1 (inactive form) (p<0.0001), while this was not observed in the K cybrids (p=0.2). K cybrids had significantly higher total global methylation levels and differences in expression levels for two acetylation genes and four methylation genes. Demethylation with 5-aza-dC altered expression levels for NFkB2, while APOE transcription patterns were unchanged. Our findings support the hypothesis that mtDNA-nuclear retrograde signaling may mediate expression levels of APOE, a key factor in many age-related diseases. Future studies will focus on identification of the mitochondrial-nuclear retrograde signaling

  19. Human Y chromosome haplogroup R-V88: a paternal genetic record of early mid Holocene trans-Saharan connections and the spread of Chadic languages

    PubMed Central

    Cruciani, Fulvio; Trombetta, Beniamino; Sellitto, Daniele; Massaia, Andrea; Destro-Bisol, Giovanni; Watson, Elizabeth; Beraud Colomb, Eliane; Dugoujon, Jean-Michel; Moral, Pedro; Scozzari, Rosaria

    2010-01-01

    Although human Y chromosomes belonging to haplogroup R1b are quite rare in Africa, being found mainly in Asia and Europe, a group of chromosomes within the paragroup R-P25* are found concentrated in the central-western part of the African continent, where they can be detected at frequencies as high as 95%. Phylogenetic evidence and coalescence time estimates suggest that R-P25* chromosomes (or their phylogenetic ancestor) may have been carried to Africa by an Asia-to-Africa back migration in prehistoric times. Here, we describe six new mutations that define the relationships among the African R-P25* Y chromosomes and between these African chromosomes and earlier reported R-P25 Eurasian sub-lineages. The incorporation of these new mutations into a phylogeny of the R1b haplogroup led to the identification of a new clade (R1b1a or R-V88) encompassing all the African R-P25* and about half of the few European/west Asian R-P25* chromosomes. A worldwide phylogeographic analysis of the R1b haplogroup provided strong support to the Asia-to-Africa back-migration hypothesis. The analysis of the distribution of the R-V88 haplogroup in >1800 males from 69 African populations revealed a striking genetic contiguity between the Chadic-speaking peoples from the central Sahel and several other Afroasiatic-speaking groups from North Africa. The R-V88 coalescence time was estimated at 9200–5600 kya, in the early mid Holocene. We suggest that R-V88 is a paternal genetic record of the proposed mid-Holocene migration of proto-Chadic Afroasiatic speakers through the Central Sahara into the Lake Chad Basin, and geomorphological evidence is consistent with this view. PMID:20051990

  20. On the Y-chromosome haplogroup C3c classification.

    PubMed

    Malyarchuk, Boris A; Derenko, Miroslava; Denisova, Galina

    2012-10-01

    As there are ambiguities in classification of the Y-chromosome haplogroup C3c, relatively frequent in populations of Northern Asia, we analyzed all three haplogroup-defining markers M48, M77 and M86 in C3-M217-individuals from Siberia, Eastern Asia and Eastern Europe. We have found that haplogroup C3c is characterized by the derived state at M48, whereas mutations at both M77 and M86 define subhaplogroup C3c1. The branch defined by M48 alone would belong to subhaplogroup C3c*, characteristic for some populations of Central and Eastern Siberia, such as Koryaks, Evens, Evenks and Yukaghirs. Subhaplogroup C3c* individuals could be considered as remnants of the Neolithic population of Siberia, based on the age of C3c*-short tandem repeat variation amounting to 4.5 ± 2.4 thousand years. PMID:22810113

  1. Temporal labyrinths of eastern Eurasian Pleistocene humans

    PubMed Central

    Wu, Xiu-Jie; Crevecoeur, Isabelle; Liu, Wu; Xing, Song; Trinkaus, Erik

    2014-01-01

    One of the morphological features that has been identified as uniquely derived for the western Eurasian Neandertals concerns the relative sizes and positions of their semicircular canals. In particular, they exhibit a relatively small anterior canal, a relatively larger lateral one, and a more inferior position of the posterior one relative to the lateral one. These discussions have not included full paleontological data on eastern Eurasian Pleistocene human temporal labyrinths, which have the potential to provide a broader context for assessing Pleistocene Homo trait polarities. We present the temporal labyrinths of four eastern Eurasian Pleistocene Homo, one each of Early (Lantian 1), Middle (Hexian 1), and Late (Xujiayao 15) Pleistocene archaic humans and one early modern human (Liujiang 1). The labyrinths of the two earlier specimens and the most recent one conform to the proportions seen among western early and recent modern humans, reinforcing the modern human pattern as generally ancestral for the genus Homo. The labyrinth of Xujiayao 15 is in the middle of the Neandertal variation and separate from the other samples. This eastern Eurasian labyrinthine dichotomy occurs in the context of none of the distinctive Neandertal external temporal or other cranial features. As such, it raises questions regarding possible cranial and postcranial morphological correlates of Homo labyrinthine variation, the use of individual “Neandertal” features for documenting population affinities, and the nature of late archaic human variation across Eurasia. PMID:25002467

  2. Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

    PubMed Central

    Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

    2015-01-01

    The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

  3. Mitochondrial DNA diversity in the African American population.

    PubMed

    Johnson, Derek C; Shrestha, Sadeep; Wiener, Howard W; Makowsky, Robert; Kurundkar, Ashish; Wilson, Craig M; Aissani, Brahim

    2015-06-01

    Genetic polymorphism along mitochondrial DNA (mtDNA) defines population-specific signatures called mtDNA haplogroups. Estimation of mtDNA haplogroup distribution may be prone to errors, notably if the study sample is not drawn from a multicenter cohort. Here, we report on mtDNA diversity in a sample of African American individuals (n = 343) enrolled in a multicenter cohort. Sequencing of the hypervariable regions I and II of the D-loop control region showed that the most common mitochondrial variants are 73G, 146C, 150T, 152C, 189G, 16278T, and 16311C. In agreement with the published data, we observed 17 common mtDNA haplogroups: L0, L1, L1b, L1c, L2, L2a, L2b, L2c, L2e, L3, L3b, L3d, L3e, L3f, L3h, L3x, and L4. The most commonly observed haplogroup is L2a (19.8%), followed by L1b (10.2%). Overall, the observed mtDNA haplogroup distribution in our study is similar to those published for the African American and the African populations. PMID:24102597

  4. Mitochondrial DNA diversity in the African American population

    PubMed Central

    Johnson, Derek C.; Shrestha, Sadeep; Wiener, Howard W.; Makowsky, Robert; Kurundkar, Ashish; Wilson, Craig M.; Aissani, Brahim

    2014-01-01

    Genetic polymorphism along mitochondrial DNA (mtDNA) defines population-specific signatures called mtDNA haplogroups. Estimation of mtDNA haplogroup distribution may be prone to errors, notably if the study sample is not drawn from a multicenter cohort. Here, we report on mtDNA diversity in a sample of African American individuals (n = 343) enrolled in a multicenter cohort. Sequencing of the hypervariable regions I and II of the D-loop control region showed that the most common mitochondrial variants are 73G, 146C, 150T, 152C, 189G, 16278T, and 16311C. In agreement with the published data, we observed 17 common mtDNA haplogroups: L0, L1, L1b, L1c, L2, L2a, L2b, L2c, L2e, L3, L3b, L3d, L3e, L3f, L3h, L3x, and L4. The most commonly observed haplogroup is L2a (19.8%), followed by L1b (10.2%). Overall, the observed mtDNA haplogroup distribution in our study is similar to those published for the African American and the African populations. PMID:24102597

  5. Mitochondrial genome diversity in the Tubalar, Even, and Ulchi: contribution to prehistory of native Siberians and their affinities to Native Americans.

    PubMed

    Sukernik, Rem I; Volodko, Natalia V; Mazunin, Ilya O; Eltsov, Nikolai P; Dryomov, Stanislav V; Starikovskaya, Elena B

    2012-05-01

    To fill remaining gaps in mitochondrial DNA diversity in the least surveyed eastern and western flanks of Siberia, 391 mtDNA samples (144 Tubalar from Altai, 87 Even from northeastern Siberia, and 160 Ulchi from the Russian Far East) were characterized via high-resolution restriction fragment length polymorphism/single nucleotide polymorphisms analysis. The subhaplogroup structure was extended through complete sequencing of 67 mtDNA samples selected from these and other related native Siberians. Specifically, we have focused on the evolutionary histories of the derivatives of M and N haplogroups, putatively reflecting different phases of settling Siberia by early modern humans. Population history and phylogeography of the resulting mtDNA genomes, combined with those from previously published data sets, revealed a wide range of tribal- and region-specific mtDNA haplotypes that emerged or diversified in Siberia before or after the last glacial maximum, ∼18 kya. Spatial distribution and ages of the "east" and "west" Eurasian mtDNA haploclusters suggest that anatomically modern humans that originally colonized Altai derived from macrohaplogroup N and came from Southwest Asia around 38,000 years ago. The derivatives of macrohaplogroup M, which largely emerged or diversified within the Russian Far East, came along with subsequent migrations to West Siberia millennia later. The last glacial maximum played a critical role in the timing and character of the settlement of the Siberian subcontinent. PMID:22487888

  6. A South American Prehistoric Mitogenome: Context, Continuity, and the Origin of Haplogroup C1d

    PubMed Central

    Sans, Mónica; Figueiro, Gonzalo; Hughes, Cris E.; Lindo, John; Hidalgo, Pedro C.; Malhi, Ripan S.

    2015-01-01

    Based on mitochondrial DNA (mtDNA), it has been estimated that at least 15 founder haplogroups peopled the Americas. Subhaplogroup C1d3 was defined based on the mitogenome of a living individual from Uruguay that carried a lineage previously identified in hypervariable region I sequences from ancient and modern Uruguayan individuals. When complete mitogenomes were studied, additional substitutions were found in the coding region of the mitochondrial genome. Using a complete ancient mitogenome and three modern mitogenomes, we aim to clarify the ancestral state of subhaplogroup C1d3 and to better understand the peopling of the region of the Río de la Plata basin, as well as of the builders of the mounds from which the ancient individuals were recovered. The ancient mitogenome, belonging to a female dated to 1,610±46 years before present, was identical to the mitogenome of one of the modern individuals. All individuals share the mutations defining subhaplogroup C1d3. We estimated an age of 8,974 (5,748–12,261) years for the most recent common ancestor of C1d3, in agreement with the initial peopling of the geographic region. No individuals belonging to the defined lineage were found outside of Uruguay, which raises questions regarding the mobility of the prehistoric inhabitants of the country. Moreover, the present study shows the continuity of Native lineages over at least 6,000 years. PMID:26509686

  7. A South American Prehistoric Mitogenome: Context, Continuity, and the Origin of Haplogroup C1d.

    PubMed

    Sans, Mónica; Figueiro, Gonzalo; Hughes, Cris E; Lindo, John; Hidalgo, Pedro C; Malhi, Ripan S

    2015-01-01

    Based on mitochondrial DNA (mtDNA), it has been estimated that at least 15 founder haplogroups peopled the Americas. Subhaplogroup C1d3 was defined based on the mitogenome of a living individual from Uruguay that carried a lineage previously identified in hypervariable region I sequences from ancient and modern Uruguayan individuals. When complete mitogenomes were studied, additional substitutions were found in the coding region of the mitochondrial genome. Using a complete ancient mitogenome and three modern mitogenomes, we aim to clarify the ancestral state of subhaplogroup C1d3 and to better understand the peopling of the region of the Río de la Plata basin, as well as of the builders of the mounds from which the ancient individuals were recovered. The ancient mitogenome, belonging to a female dated to 1,610±46 years before present, was identical to the mitogenome of one of the modern individuals. All individuals share the mutations defining subhaplogroup C1d3. We estimated an age of 8,974 (5,748-12,261) years for the most recent common ancestor of C1d3, in agreement with the initial peopling of the geographic region. No individuals belonging to the defined lineage were found outside of Uruguay, which raises questions regarding the mobility of the prehistoric inhabitants of the country. Moreover, the present study shows the continuity of Native lineages over at least 6,000 years. PMID:26509686

  8. Deep Phylogenetic Analysis of Haplogroup G1 Provides Estimates of SNP and STR Mutation Rates on the Human Y-Chromosome and Reveals Migrations of Iranic Speakers

    PubMed Central

    Balanovsky, Oleg; Zhabagin, Maxat; Agdzhoyan, Anastasiya; Chukhryaeva, Marina; Zaporozhchenko, Valery; Utevska, Olga; Highnam, Gareth; Sabitov, Zhaxylyk; Greenspan, Elliott; Dibirova, Khadizhat; Skhalyakho, Roza; Kuznetsova, Marina; Koshel, Sergey; Yusupov, Yuldash; Nymadawa, Pagbajabyn; Zhumadilov, Zhaxybay; Pocheshkhova, Elvira; Haber, Marc; A. Zalloua, Pierre; Yepiskoposyan, Levon; Dybo, Anna; Tyler-Smith, Chris; Balanovska, Elena

    2015-01-01

    Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of South-West and Central Asia but reaches up to 80% frequency in some populations scattered within this area. We have genotyped the G1-defining marker M285 in 27 Eurasian populations (n= 5,346), analyzed 367 M285-positive samples using 17 Y-STRs, and sequenced ~11 Mb of the Y-chromosome in 20 of these samples to an average coverage of 67X. This allowed detailed phylogenetic reconstruction. We identified five branches, all with high geographical specificity: G1-L1323 in Kazakhs, the closely related G1-GG1 in Mongols, G1-GG265 in Armenians and its distant brother clade G1-GG162 in Bashkirs, and G1-GG362 in West Indians. The haplotype diversity, which decreased from West Iran to Central Asia, allows us to hypothesize that this rare haplogroup could have been carried by the expansion of Iranic speakers northwards to the Eurasian steppe and via founder effects became a predominant genetic component of some populations, including the Argyn tribe of the Kazakhs. The remarkable agreement between genetic and genealogical trees of Argyns allowed us to calibrate the molecular clock using a historical date (1405 AD) of the most recent common genealogical ancestor. The mutation rate for Y-chromosomal sequence data obtained was 0.78×10-9 per bp per year, falling within the range of published rates. The mutation rate for Y-chromosomal STRs was 0.0022 per locus per generation, very close to the so-called genealogical rate. The “clan-based” approach to estimating the mutation rate provides a third, middle way between direct farther-to-son comparisons and using archeologically known migrations, whose dates are subject to revision and of uncertain relationship to genetic events. PMID:25849548

  9. Eurasian Arctic abyssal waters are warming

    NASA Astrophysics Data System (ADS)

    Schauer, Ursula; von Appen, Wilken-Jon; Somavilla Cabrillo, Raquel; Behrendt, Axel; Rabe, Benjamin

    2016-04-01

    In the past decades, not only the upper water layers, but also the deepest layers of the Arctic Ocean have been warming. Observations show that the rate of warming varies markedly in the different basins with the fastest warming in the deep Greenland Sea (ca. 0.11°C per decade) and the Eurasian Basin featuring an average rate of ca. 0.01°C per decade. While the warming in the Greenland Sea is attributed to ongoing export of relatively warmer deep waters from the Arctic Ocean in combination with the halt of deep convection, the reason of Eurasian Basin deep warming is less clear. We discuss possible causes such as changes in the abyssal ventilation through slope convection, advection from other basins and/or geothermal heating through various sources.

  10. Mitochondrial DNA analysis shows a Near Eastern Neolithic origin for domestic cattle and no indication of domestication of European aurochs

    PubMed Central

    Edwards, Ceiridwen J; Bollongino, Ruth; Scheu, Amelie; Chamberlain, Andrew; Tresset, Anne; Vigne, Jean-Denis; Baird, Jillian F; Larson, Greger; Ho, Simon Y.W; Heupink, Tim H; Shapiro, Beth; Freeman, Abigail R; Thomas, Mark G; Arbogast, Rose-Marie; Arndt, Betty; Bartosiewicz, László; Benecke, Norbert; Budja, Mihael; Chaix, Louis; Choyke, Alice M; Coqueugniot, Eric; Döhle, Hans-Jürgen; Göldner, Holger; Hartz, Sönke; Helmer, Daniel; Herzig, Barabara; Hongo, Hitomi; Mashkour, Marjan; Özdogan, Mehmet; Pucher, Erich; Roth, Georg; Schade-Lindig, Sabine; Schmölcke, Ulrich; Schulting, Rick J; Stephan, Elisabeth; Uerpmann, Hans-Peter; Vörös, István; Voytek, Barbara; Bradley, Daniel G; Burger, Joachim

    2007-01-01

    The extinct aurochs (Bos primigenius primigenius) was a large type of cattle that ranged over almost the whole Eurasian continent. The aurochs is the wild progenitor of modern cattle, but it is unclear whether European aurochs contributed to this process. To provide new insights into the demographic history of aurochs and domestic cattle, we have generated high-confidence mitochondrial DNA sequences from 59 archaeological skeletal finds, which were attributed to wild European cattle populations based on their chronological date and/or morphology. All pre-Neolithic aurochs belonged to the previously designated P haplogroup, indicating that this represents the Late Glacial Central European signature. We also report one new and highly divergent haplotype in a Neolithic aurochs sample from Germany, which points to greater variability during the Pleistocene. Furthermore, the Neolithic and Bronze Age samples that were classified with confidence as European aurochs using morphological criteria all carry P haplotype mitochondrial DNA, suggesting continuity of Late Glacial and Early Holocene aurochs populations in Europe. Bayesian analysis indicates that recent population growth gives a significantly better fit to our data than a constant-sized population, an observation consistent with a postglacial expansion scenario, possibly from a single European refugial population. Previous work has shown that most ancient and modern European domestic cattle carry haplotypes previously designated T. This, in combination with our new finding of a T haplotype in a very Early Neolithic site in Syria, lends persuasive support to a scenario whereby gracile Near Eastern domestic populations, carrying predominantly T haplotypes, replaced P haplotype-carrying robust autochthonous aurochs populations in Europe, from the Early Neolithic onward. During the period of coexistence, it appears that domestic cattle were kept separate from wild aurochs and introgression was extremely rare. PMID

  11. Eurasian Heat Waves: Mechanisms and Predictability

    NASA Technical Reports Server (NTRS)

    Wang, Hailan; Schubert, Siegfried; Koster, Randal; Suarez, Max

    2012-01-01

    This study uses the NASA MERRA reanalysis and GEOS 5 model simulations to examine the causes of Eurasian heat waves including the recent extreme events that occurred in Europe during 2003 and in Russia during 2010. The focus is on the warm season and the part of the Eurasian continent that extends north of about 40oN, or roughly to the north of the mean upper tropospheric jet stream. The results show that such extreme events are an amplification of natural patterns of atmospheric variability that develop over the Eurasian continent as a result of internal atmospheric forcing. The amplification occurs when the wave occasionally becomes locked in place for several weeks to months resulting in extreme heat and drying with the location depending on the phase of the upper atmospheric wave. An ensemble of very long GEOS-S model simulations (spanning the 20th century) forced with observed SST and greenhouse gases show that the model is capable of generating very similar heat waves, and that they have become more intense in the last thirty years as a result of the overall warming of the Asian continent. Sensitivity experiments with perturbed initial conditions indicate that these events have limited predictability.

  12. Large-Scale Genetic Structuring of a Widely Distributed Carnivore - The Eurasian Lynx (Lynx lynx)

    PubMed Central

    Rueness, Eli K.; Naidenko, Sergei; Trosvik, Pål; Stenseth, Nils Chr.

    2014-01-01

    Over the last decades the phylogeography and genetic structure of a multitude of species inhabiting Europe and North America have been described. The flora and fauna of the vast landmasses of north-eastern Eurasia are still largely unexplored in this respect. The Eurasian lynx is a large felid that is relatively abundant over much of the Russian sub-continent and the adjoining countries. Analyzing 148 museum specimens collected throughout its range over the last 150 years we have described the large-scale genetic structuring in this highly mobile species. We have investigated the spatial genetic patterns using mitochondrial DNA sequences (D-loop and cytochrome b) and 11 microsatellite loci, and describe three phylogenetic clades and a clear structuring along an east-west gradient. The most likely scenario is that the contemporary Eurasian lynx populations originated in central Asia and that parts of Europe were inhabited by lynx during the Pleistocene. After the Last Glacial Maximum (LGM) range expansions lead to colonization of north-western Siberia and Scandinavia from the Caucasus and north-eastern Siberia from a refugium further east. No evidence of a Berinigan refugium could be detected in our data. We observed restricted gene flow and suggest that future studies of the Eurasian lynx explore to what extent the contemporary population structure may be explained by ecological variables. PMID:24695745

  13. Mitochondrial DNA diversity and the origin of Chinese indigenous sheep.

    PubMed

    Zhao, Erhu; Yu, Qian; Zhang, Nanyang; Kong, Deying; Zhao, Yongju

    2013-11-01

    Large-scale mitochondrial DNA (mtDNA) D-loop sequences data from previous studies were investigated to obtain genetic information which contributes to a better understanding of the genetic diversity and history of modern sheep. In this study, we analyzed mtDNA D-loop sequences of 963 individuals from 16 Chinese indigenous breeds that distributed seven geographic regions. Phylogenetic analysis showed that all three previously defined haplogroups A, B, and C were found in all breeds among different regions except in Southwest China mountainous region, which had only the A and B haplogroups. The weak phylogeographic structure was observed among Chinese indigenous sheep breeds distribution regions and this could be attributable to long-term strong gene flow among regions induced by the human migration, commercial trade, and extensive transport of sheep. The estimation of demographic parameters from mismatch analyses showed that haplogroups A and B had at least one demographic expansion of indigenous sheep in China. PMID:23709123

  14. Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

    PubMed Central

    Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

    2014-01-01

    Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be

  15. Haplogroup Classification of Korean Cattle Breeds Based on Sequence Variations of mtDNA Control Region.

    PubMed

    Kim, Jae-Hwan; Lee, Seong-Su; Kim, Seung Chang; Choi, Seong-Bok; Kim, Su-Hyun; Lee, Chang Woo; Jung, Kyoung-Sub; Kim, Eun Sung; Choi, Young-Sun; Kim, Sung-Bok; Kim, Woo Hyun; Cho, Chang-Yeon

    2016-05-01

    Many studies have reported the frequency and distribution of haplogroups among various cattle breeds for verification of their origins and genetic diversity. In this study, 318 complete sequences of the mtDNA control region from four Korean cattle breeds were used for haplogroup classification. 71 polymorphic sites and 66 haplotypes were found in these sequences. Consistent with the genetic patterns in previous reports, four haplogroups (T1, T2, T3, and T4) were identified in Korean cattle breeds. In addition, T1a, T3a, and T3b sub-haplogroups were classified. In the phylogenetic tree, each haplogroup formed an independent cluster. The frequencies of T3, T4, T1 (containing T1a), and T2 were 66%, 16%, 10%, and 8%, respectively. Especially, the T1 haplogroup contained only one haplotype and a sample. All four haplogroups were found in Chikso, Jeju black and Hanwoo. However, only the T3 and T4 haplogroups appeared in Heugu, and most Chikso populations showed a partial of four haplogroups. These results will be useful for stable conservation and efficient management of Korean cattle breeds. PMID:26954229

  16. Haplogroup Classification of Korean Cattle Breeds Based on Sequence Variations of mtDNA Control Region

    PubMed Central

    Kim, Jae-Hwan; Lee, Seong-Su; Kim, Seung Chang; Choi, Seong-Bok; Kim, Su-Hyun; Lee, Chang Woo; Jung, Kyoung-Sub; Kim, Eun Sung; Choi, Young-Sun; Kim, Sung-Bok; Kim, Woo Hyun; Cho, Chang-Yeon

    2016-01-01

    Many studies have reported the frequency and distribution of haplogroups among various cattle breeds for verification of their origins and genetic diversity. In this study, 318 complete sequences of the mtDNA control region from four Korean cattle breeds were used for haplogroup classification. 71 polymorphic sites and 66 haplotypes were found in these sequences. Consistent with the genetic patterns in previous reports, four haplogroups (T1, T2, T3, and T4) were identified in Korean cattle breeds. In addition, T1a, T3a, and T3b sub-haplogroups were classified. In the phylogenetic tree, each haplogroup formed an independent cluster. The frequencies of T3, T4, T1 (containing T1a), and T2 were 66%, 16%, 10%, and 8%, respectively. Especially, the T1 haplogroup contained only one haplotype and a sample. All four haplogroups were found in Chikso, Jeju black and Hanwoo. However, only the T3 and T4 haplogroups appeared in Heugu, and most Chikso populations showed a partial of four haplogroups. These results will be useful for stable conservation and efficient management of Korean cattle breeds. PMID:26954229

  17. Pleistocene Chinese cave hyenas and the recent Eurasian history of the spotted hyena, Crocuta crocuta.

    PubMed

    Sheng, Gui-Lian; Soubrier, Julien; Liu, Jin-Yi; Werdelin, Lars; Llamas, Bastien; Thomson, Vicki A; Tuke, Jonathan; Wu, Lian-Juan; Hou, Xin-Dong; Chen, Quan-Jia; Lai, Xu-Long; Cooper, Alan

    2014-02-01

    The living hyena species (spotted, brown, striped and aardwolf) are remnants of a formerly diverse group of more than 80 fossil species, which peaked in diversity in the Late Miocene (about 7-8 Ma). The fossil history indicates an African origin, and morphological and ancient DNA data have confirmed that living spotted hyenas (Crocuta crocuta) of Africa were closely related to extinct Late Pleistocene cave hyenas from Europe and Asia. The current model used to explain the origins of Eurasian cave hyena populations invokes multiple migrations out of Africa between 3.5-0.35 Ma. We used mitochondrial DNA sequences from radiocarbon-dated Chinese Pleistocene hyena specimens to examine the origin of Asian populations, and temporally calibrate the evolutionary history of spotted hyenas. Our results support a far more recent evolutionary timescale (430-163 kya) and suggest that extinct and living spotted hyena populations originated from a widespread Eurasian population in the Late Pleistocene, which was only subsequently restricted to Africa. We developed statistical tests of the contrasting population models and their fit to the fossil record. Coalescent simulations and Bayes Factor analysis support the new radiocarbon-calibrated timescale and Eurasian origins model. The new Eurasian biogeographic scenario proposed for the hyena emphasizes the role of the vast steppe grasslands of Eurasia in contrast to models only involving Africa. The new methodology for combining genetic and geological data to test contrasting models of population history will be useful for a wide range of taxa where ancient and historic genetic data are available. PMID:24320717

  18. Human Y Chromosome Haplogroup N: A Non-trivial Time-Resolved Phylogeography that Cuts across Language Families.

    PubMed

    Ilumäe, Anne-Mai; Reidla, Maere; Chukhryaeva, Marina; Järve, Mari; Post, Helen; Karmin, Monika; Saag, Lauri; Agdzhoyan, Anastasiya; Kushniarevich, Alena; Litvinov, Sergey; Ekomasova, Natalya; Tambets, Kristiina; Metspalu, Ene; Khusainova, Rita; Yunusbayev, Bayazit; Khusnutdinova, Elza K; Osipova, Ludmila P; Fedorova, Sardana; Utevska, Olga; Koshel, Sergey; Balanovska, Elena; Behar, Doron M; Balanovsky, Oleg; Kivisild, Toomas; Underhill, Peter A; Villems, Richard; Rootsi, Siiri

    2016-07-01

    The paternal haplogroup (hg) N is distributed from southeast Asia to eastern Europe. The demographic processes that have shaped the vast extent of this major Y chromosome lineage across numerous linguistically and autosomally divergent populations have previously been unresolved. On the basis of 94 high-coverage re-sequenced Y chromosomes, we establish and date a detailed hg N phylogeny. We evaluate geographic structure by using 16 distinguishing binary markers in 1,631 hg N Y chromosomes from a collection of 6,521 samples from 56 populations. The more southerly distributed sub-clade N4 emerged before N2a1 and N3, found mostly in the north, but the latter two display more elaborate branching patterns, indicative of regional contrasts in recent expansions. In particular, a number of prominent and well-defined clades with common N3a3'6 ancestry occur in regionally dissimilar northern Eurasian populations, indicating almost simultaneous regional diversification and expansion within the last 5,000 years. This patrilineal genetic affinity is decoupled from the associated higher degree of language diversity. PMID:27392075

  19. Revealing latitudinal patterns of mitochondrial DNA diversity in Chileans.

    PubMed

    Gómez-Carballa, Alberto; Moreno, Fabián; Álvarez-Iglesias, Vanesa; Martinón-Torres, Federico; García-Magariños, Manuel; Pantoja-Astudillo, Jaime A; Aguirre-Morales, Eugenia; Bustos, Patricio; Salas, Antonio

    2016-01-01

    The territory of Chile is particularly long and narrow, which combined with its mountainous terrain, makes it a unique scenario for human genetic studies. We obtained 995 control region mitochondrial DNA (mtDNA) sequences from Chileans representing populations living at different latitudes of the country from the North to the southernmost region. The majority of the mtDNA profiles are of Native American origin (∼88%). The remaining haplotypes are mostly of recent European origin (∼11%), and only a minor proportion is of recent African ancestry (∼1%). While these proportions are relatively uniform across the country, more structured patterns of diversity emerge when examining the variation from a phylogeographic perspective. For instance, haplogroup A2 reaches ∼9% in the North, and its frequency decreases gradually to ∼1% in the southernmost populations, while the frequency of haplogroup D (sub-haplogroups D1 and D4) follows the opposite pattern: 36% in the southernmost region, gradually decreasing to 21% in the North. Furthermore, there are remarkable signatures of founder effects in specific sub-clades of Native American (e.g. haplogroups D1j and D4p) and European (e.g. haplogroups T2b3 and K1a4a1a+195) ancestry. We conclude that the magnitude of the latitudinal differences observed in the patterns of mtDNA variation might be relevant in forensic casework. PMID:26517175

  20. The Molecular Dissection of mtDNA Haplogroup H Confirms That the Franco-Cantabrian Glacial Refuge Was a Major Source for the European Gene Pool

    PubMed Central

    Achilli, Alessandro; Rengo, Chiara; Magri, Chiara; Battaglia, Vincenza; Olivieri, Anna; Scozzari, Rosaria; Cruciani, Fulvio; Zeviani, Massimo; Briem, Egill; Carelli, Valerio; Moral, Pedro; Dugoujon, Jean-Michel; Roostalu, Urmas; Loogväli, Eva-Liis; Kivisild, Toomas; Bandelt, Hans-Jürgen; Richards, Martin; Villems, Richard; Santachiara-Benerecetti, A. Silvana; Semino, Ornella; Torroni, Antonio

    2004-01-01

    Complete sequencing of 62 mitochondrial DNAs (mtDNAs) belonging (or very closely related) to haplogroup H revealed that this mtDNA haplogroup—by far the most common in Europe—is subdivided into numerous subhaplogroups, with at least 15 of them (H1–H15) identifiable by characteristic mutations. All the haplogroup H mtDNAs found in 5,743 subjects from 43 populations were then screened for diagnostic markers of subhaplogroups H1 and H3. This survey showed that both subhaplogroups display frequency peaks, centered in Iberia and surrounding areas, with distributions declining toward the northeast and southeast—a pattern extremely similar to that previously reported for mtDNA haplogroup V. Furthermore, the coalescence ages of H1 and H3 (∼11,000 years) are close to that previously reported for V. These findings have major implications for the origin of Europeans, since they attest that the Franco-Cantabrian refuge area was indeed the source of late-glacial expansions of hunter-gatherers that repopulated much of Central and Northern Europe from ∼15,000 years ago. This has also some implications for disease studies. For instance, the high occurrence of H1 and H3 in Iberia led us to re-evaluate the haplogroup distribution in 50 Spanish families affected by nonsyndromic sensorineural deafness due to the A1555G mutation. The survey revealed that the previously reported excess of H among these families is caused entirely by H3 and is due to a major, probably nonrecent, founder event. PMID:15382008

  1. Genome-wide Evidence Reveals that African and Eurasian Golden Jackals Are Distinct Species.

    PubMed

    Koepfli, Klaus-Peter; Pollinger, John; Godinho, Raquel; Robinson, Jacqueline; Lea, Amanda; Hendricks, Sarah; Schweizer, Rena M; Thalmann, Olaf; Silva, Pedro; Fan, Zhenxin; Yurchenko, Andrey A; Dobrynin, Pavel; Makunin, Alexey; Cahill, James A; Shapiro, Beth; Álvares, Francisco; Brito, José C; Geffen, Eli; Leonard, Jennifer A; Helgen, Kristofer M; Johnson, Warren E; O'Brien, Stephen J; Van Valkenburgh, Blaire; Wayne, Robert K

    2015-08-17

    The golden jackal of Africa (Canis aureus) has long been considered a conspecific of jackals distributed throughout Eurasia, with the nearest source populations in the Middle East. However, two recent reports found that mitochondrial haplotypes of some African golden jackals aligned more closely to gray wolves (Canis lupus), which is surprising given the absence of gray wolves in Africa and the phenotypic divergence between the two species. Moreover, these results imply the existence of a previously unrecognized phylogenetically distinct species despite a long history of taxonomic work on African canids. To test the distinct-species hypothesis and understand the evolutionary history that would account for this puzzling result, we analyzed extensive genomic data including mitochondrial genome sequences, sequences from 20 autosomal loci (17 introns and 3 exon segments), microsatellite loci, X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences, and whole-genome nuclear sequences in African and Eurasian golden jackals and gray wolves. Our results provide consistent and robust evidence that populations of golden jackals from Africa and Eurasia represent distinct monophyletic lineages separated for more than one million years, sufficient to merit formal recognition as different species: C. anthus (African golden wolf) and C. aureus (Eurasian golden jackal). Using morphologic data, we demonstrate a striking morphologic similarity between East African and Eurasian golden jackals, suggesting parallelism, which may have misled taxonomists and likely reflects uniquely intense interspecific competition in the East African carnivore guild. Our study shows how ecology can confound taxonomy if interspecific competition constrains size diversification. PMID:26234211

  2. Mitochondrial DNA polymorphisms in Chilean aboriginal populations: implications for the peopling of the southern cone of the continent.

    PubMed

    Moraga, M L; Rocco, P; Miquel, J F; Nervi, F; Llop, E; Chakraborty, R; Rothhammer, F; Carvallo, P

    2000-09-01

    The mitochondrial DNAs (mtDNAs) from individuals belonging to three Chilean tribes, the Mapuche, the Pehuenche, and the Yaghan, were studied both by RFLP analysis and D-loop (control region) sequencing. RFLP analysis showed that 3 individuals (1.3%) belonged to haplogroup A, 19 (8%) to haplogroup B, 102 (43%) to haplogroup C, and 113 (47.7%) to haplogroup D. Among the 73 individuals analyzed by D-loop sequencing, we observed 37 different haplotypes defined by 52 polymorphic sites. Joint analysis of data obtained by RFLP and sequencing methods demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of these three contemporary South American aborigine groups clustered into four main haplogroups, in a way similar to those previously described for other Amerindians. These results further revealed the absence of haplogroup A in both the Mapuche and Yaghan as well as the absence of haplogroup B in the Yaghan. These results suggest that the people of Tierra del Fuego are related to tribes from south-central South America. PMID:10954617

  3. Pan Eurasian Experiment (PEEX): a new research initiative focused on the Northern Pan-Eurasian Region

    NASA Astrophysics Data System (ADS)

    Petäjä, Tuukka; Lappalainen, Hanna; Zaytseva, Nina; Shvidenko, Anatoli; Kujansuu, Joni; Kerminen, Veli-Matti; Viisanen, Yrjö; Kotlyakov, Vladimir; Kasimov, Nikolai; Bondur, Valery; Matvienko, Gennadi; Zilitinkevich, Sergej; Kulmala, Markku

    2014-05-01

    The increasing human activities are changing the environment and the humanity is we are pushing the safe boundaries of the globe. It is of utmost importance to gauge with a comprehensive research program on the current status of the environment, particularly in the most vulnerable locations. Pan-Eurasian Experiment (PEEX) is a new multidisciplinary research approach aiming at resolving the major uncertainties in the Earth system science and global sustainability questions in the Arctic and boreal Pan-Eurasian regions. The PEEX program aims (i) to understand the Earth system and the influence of environmental and societal changes in pristine and industrialized Pan-Eurasian environments, (ii) to establish and sustain long-term, continuous and comprehensive ground-based airborne and seaborne research infrastructures, and to utilize satellite data and multi-scale model frameworks, (iii) to contribute to regional climate scenarios in the northern Pan-Eurasia and determine the relevant factors and interactions influencing human and societal wellbeing (iv) to promote the dissemination of PEEX scientific results and strategies in scientific and stake-holder communities and policy making, (v) to educate the next generation of multidisciplinary global change experts and scientists, and (vi) to increase the public awareness of climate change impacts in the Pan-Eurasian region. The development of PEEX research infrastructure will be one of the first activities of PEEX. PEEX will find synergies with the major European land-atmosphere observation infrastructures such as ICOS a research infrastructure to decipher the greenhouse gas balance of Europe and adjacent regions, ACTRIS (Aerosols, Clouds, and Trace gases Research InfraStructure Network-project), and ANAEE (The experimentation in terrestrial ecosystem research) networks and with the flag ship stations like the SMEARs (Station for Measuring Ecosystem-Atmosphere Relations) when design, re-organizing and networking existing

  4. East Eurasian ancestry in the middle of Europe: genetic footprints of Steppe nomads in the genomes of Belarusian Lipka Tatars

    PubMed Central

    Pankratov, Vasili; Litvinov, Sergei; Kassian, Alexei; Shulhin, Dzmitry; Tchebotarev, Lieve; Yunusbayev, Bayazit; Möls, Märt; Sahakyan, Hovhannes; Yepiskoposyan, Levon; Rootsi, Siiri; Metspalu, Ene; Golubenko, Maria; Ekomasova, Natalia; Akhatova, Farida; Khusnutdinova, Elza; Heyer, Evelyne; Endicott, Phillip; Derenko, Miroslava; Malyarchuk, Boris; Metspalu, Mait; Davydenko, Oleg; Villems, Richard; Kushniarevich, Alena

    2016-01-01

    Medieval era encounters of nomadic groups of the Eurasian Steppe and largely sedentary East Europeans had a variety of demographic and cultural consequences. Amongst these outcomes was the emergence of the Lipka Tatars—a Slavic-speaking Sunni-Muslim minority residing in modern Belarus, Lithuania and Poland, whose ancestors arrived in these territories via several migration waves, mainly from the Golden Horde. Our results show that Belarusian Lipka Tatars share a substantial part of their gene pool with Europeans as indicated by their Y-chromosomal, mitochondrial and autosomal DNA variation. Nevertheless, Belarusian Lipkas still retain a strong genetic signal of their nomadic ancestry, witnessed by the presence of common Y-chromosomal and mitochondrial DNA variants as well as autosomal segments identical by descent between Lipkas and East Eurasians from temperate and northern regions. Hence, we document Lipka Tatars as a unique example of former Medieval migrants into Central Europe, who became sedentary, changed language to Slavic, yet preserved their faith and retained, both uni- and bi-parentally, a clear genetic echo of a complex population interplay throughout the Eurasian Steppe Belt, extending from Central Europe to northern China. PMID:27453128

  5. East Eurasian ancestry in the middle of Europe: genetic footprints of Steppe nomads in the genomes of Belarusian Lipka Tatars.

    PubMed

    Pankratov, Vasili; Litvinov, Sergei; Kassian, Alexei; Shulhin, Dzmitry; Tchebotarev, Lieve; Yunusbayev, Bayazit; Möls, Märt; Sahakyan, Hovhannes; Yepiskoposyan, Levon; Rootsi, Siiri; Metspalu, Ene; Golubenko, Maria; Ekomasova, Natalia; Akhatova, Farida; Khusnutdinova, Elza; Heyer, Evelyne; Endicott, Phillip; Derenko, Miroslava; Malyarchuk, Boris; Metspalu, Mait; Davydenko, Oleg; Villems, Richard; Kushniarevich, Alena

    2016-01-01

    Medieval era encounters of nomadic groups of the Eurasian Steppe and largely sedentary East Europeans had a variety of demographic and cultural consequences. Amongst these outcomes was the emergence of the Lipka Tatars-a Slavic-speaking Sunni-Muslim minority residing in modern Belarus, Lithuania and Poland, whose ancestors arrived in these territories via several migration waves, mainly from the Golden Horde. Our results show that Belarusian Lipka Tatars share a substantial part of their gene pool with Europeans as indicated by their Y-chromosomal, mitochondrial and autosomal DNA variation. Nevertheless, Belarusian Lipkas still retain a strong genetic signal of their nomadic ancestry, witnessed by the presence of common Y-chromosomal and mitochondrial DNA variants as well as autosomal segments identical by descent between Lipkas and East Eurasians from temperate and northern regions. Hence, we document Lipka Tatars as a unique example of former Medieval migrants into Central Europe, who became sedentary, changed language to Slavic, yet preserved their faith and retained, both uni- and bi-parentally, a clear genetic echo of a complex population interplay throughout the Eurasian Steppe Belt, extending from Central Europe to northern China. PMID:27453128

  6. European Transmission Interconnection; Eurasian power grid

    SciTech Connect

    Posch, J. )

    1991-09-01

    Systems and philosophies perceived on a grand scale, encompassing new ideas, are often characterized as a dream. But in fact, such dreams often lead to the first step to fruitful development. This article is based on a preliminary study of the existing electrical high-tension networks of Western Europe, Eastern Europe and the Soviet Union - which, as explained herein, may be merged into a multinational energy supply system. Such a system would constitute a completely interconnected Eurasian Power Grid. The idea of a Eurasian super grid, spanning from the Atlantic to the Ural and Siberia, is not new. Various studies have been conducted by both western Europe and the Soviet Union on this topic. Our world is currently in an era of extra high voltage (EHV) and ultra high voltage (UHV) electrical systems. This translates into existing UHV lines of 1150 kV which have already been proven in successful operation. Such UHV systems are capable of transmitting thousands of megawatts over a distance of a 1000 miles. Furthermore, national boundaries are not more a hindrance than the challenge of interconnecting complete networks into an overall synchronized working system with load exchange capabilities in all directions.

  7. Mitochondrial DNA phylogeny in Eastern and Western Slavs.

    PubMed

    Malyarchuk, B; Grzybowski, T; Derenko, M; Perkova, M; Vanecek, T; Lazur, J; Gomolcak, P; Tsybovsky, I

    2008-08-01

    To resolve the phylogeny of certain mitochondrial DNA (mtDNA) haplogroups in eastern Europe and estimate their evolutionary age, a total of 73 samples representing mitochondrial haplogroups U4, HV*, and R1 were selected for complete mitochondrial genome sequencing from a collection of about 2,000 control region sequences sampled in eastern (Russians, Belorussians, and Ukrainians) and western (Poles, Czechs, and Slovaks) Slavs. On the basis of whole-genome resolution, we fully characterized a number of haplogroups (HV3, HV4, U4a1, U4a2, U4a3, U4b, U4c, U4d, and R1a) that were previously described only partially. Our findings demonstrate that haplogroups HV3, HV4, and U4a1 could be traced back to the pre-Neolithic times ( approximately 12,000-19,000 years before present [YBP]) in eastern Europe. In addition, an ancient connection between the Caucasus/Europe and India has been revealed by analysis of haplogroup R1 diversity, with a split between the Indian and Caucasus/European R1a lineages occurring about 16,500 years ago. Meanwhile, some mtDNA subgroups detected in Slavs (such as U4a2a, U4a2*, HV3a, and R1a1) are definitely younger being dated between 6,400 and 8,200 YBP. However, robust age estimations appear to be problematic due to the high ratios of nonsynonymous to synonymous substitutions found in young mtDNA subclusters. PMID:18477584

  8. Paternal lineages in Libya inferred from Y-chromosome haplogroups.

    PubMed

    Triki-Fendri, Soumaya; Sánchez-Diz, Paula; Rey-González, Danel; Ayadi, Imen; Carracedo, Ángel; Rebai, Ahmed

    2015-06-01

    Many studies based on genetic diversity of North African populations have contributed to elucidate the modelling of the genetic landscape in this region. North Africa is considered as a distinct spatial-temporal entity on geographic, archaeological, and historical grounds, which has undergone the influence of different human migrations along its shaping. For instance, Libya, a North African country, was first inhabited by Berbers and then colonized by a variety of ethnic groups like Phoenicians, Greeks, Romans, Arabs and, in recent times, Italians. In this study, we contribute to clarify the genetic variation of Libya and consequently, of North African modern populations, by the study of Libyan male lineages. A total of 22 Y-chromosome-specific SNPs were genotyped in a sample of 175 Libyan males, allowing the characterization of 18 Y-chromosomal haplogroups. The obtained data revealed a predominant Northwest African component represented by haplogroup E-M81 (33.7%) followed by J(xJ1a,J2)-M304 (27.4%), which is postulated to have a Middle Eastern origin. The comparative study with other populations (∼5,400 individuals from North Africa, Middle East, Sub-Saharan Africa, and Europe) revealed a general genetic homogeneity among North African populations (FST = 5.3 %; P-value < 0.0001). Overall, the Y-haplogroup diversity in Libya and in North Africa is characterized by two genetic components. The first signature is typical of Berber-speaking people (E-M81), the autochthonous inhabitants, whereas the second is (J(xJ1a,J2)-M304), originating from Arabic populations. This is in agreement with the hypothesis of an Arabic expansion from the Middle East, shaping the North African genetic landscape. PMID:25677690

  9. Mitochondrial haplotypes may modulate the phenotypic manifestation of the deafness-associated 12S rRNA 1555A>G mutation

    PubMed Central

    Lu, Jianxin; Qian, Yaping; Li, Zhiyuan; Yang, Aifen; Zhu, Yi; Li, Ronghua; Yang, Li; Tang, Xiaowen; Chen, Bobei; Ding, Yu; Li, Yongyan; You, Junyan; Zheng, Jing; Tao, Zhihua; Zhao, Fuxin; Wang, Jindan; Sun, Dongmei; Zhao, Jianyue; Meng, Yanzi; Guan, Min-Xin

    2009-01-01

    Mitochondrial 12S rRNA 1555A>G mutation is one of the important causes of aminoglycoside-induced and nonsyndromic deafness. Our previous investigations showed that the A1555G mutation was a primary factor underlying the development of deafness but was insufficient to produce deafness phenotype. However, it has been proposed that mitochondrial haplotypes modulate the phenotypic manifestation of the 1555A>G mutation. Here, we performed systematic and extended mutational screening of 12S rRNA gene in a cohort of 1742 hearing-impaired Han Chinese pediatric subjects from Zhejiang Province, China. Among these, 69 subjects with aminoglycoside-induced and nonsyndromic deafness harbored the homoplasmic 1555A>G mutation. These translated to a frequency of ~3.96% for the 1555A>G mutation in this hearing impaired population. Clinical and genetic characterizations of 69 Chinese families carrying the 1555A>G mutation exhibited a wide range of penetrance and expressivity of hearing impairment. The average penetrances of deafness were 29.5% and 17.6%, respectively, when aminoglycoside-induced hearing loss was included or excluded. Furthermore, the average age-of-onset for deafness without aminoglycoside exposure ranged from 5 and 30 years old, with the average of 14.5 years. Their mitochondrial genomes exhibited distinct sets of polymorphisms belonging to ten Eastern Asian haplogroups A, B, C, D, F, G, M, N, R and Y, respectively. These indicated that the 1555A>G mutation occurred through recurrent origins and founder events. The haplogroup D accounted for 40.6% of the patient’s mtDNA samples but only 25.8% of the Chinese control mtDNA samples. Strikingly, these Chinese families carrying mitochondrial haplogroup B exhibited higher penetrance and expressivity of hearing loss. In addition, the mitochondrial haplogroup specific variants: 15927G>A of haplogroup B5b, 12338T>C of haplogroup F2, 7444G>A of haplogroup B4, 5802T>C, 10454T>C, 12224C>T and 11696G>A of D4 haplogroup, 5821G

  10. Understanding the Y chromosome variation in Korea--relevance of combined haplogroup and haplotype analyses.

    PubMed

    Park, Myung Jin; Lee, Hwan Young; Yang, Woo Ick; Shin, Kyoung-Jin

    2012-07-01

    We performed a molecular characterization of Korean Y-chromosomal haplogroups using a combination of Y-chromosomal single nucleotide polymorphisms (Y-SNPs) and Y-chromosomal short tandem repeats (Y-STRs). In a test using DNA samples from 706 Korean males, a total of 19 different haplogroups were identified by 26 Y-SNPs including the newly redefined markers (PK4, KL2, and P164) in haplogroup O. When genotyping the SNPs, phylogenetic nonequivalence was found between SNPs M117 and M133, which define haplogroup O3a3c1 (O3a2c1a according to the updated tree of haplogroup O by Yan et al. (European Journal of Human Genetics 19:1013-1015, 2011)), suggesting that the position of the M133 marker should be corrected. We have shown that the haplotypes consisted of DYS392, DYS393, DYS437, DYS438, DYS448, and DYS388 loci, which exhibit a relatively lower mutation rate, can preserve phylogenetic information and hence can be used to roughly distinguish Y-chromosome haplogroups, whereas more rapidly mutating Y-STRs such as DYS449 and DYS458 are useful for differentiating male lineages. However, at the relatively rapidly mutating DYS447, DYS449, DYS458, and DYS464 loci, unusually short alleles and intermediate alleles with common sequence structures are informative for elucidating the substructure within the context of a particular haplogroup. In addition, some deletion mutations in the DYS385 flanking region and the null allele at DYS448 were associated with a single haplogroup background. These high-resolution haplogroup and haplotype data will improve our understanding of regional Y-chromosome variation or recent migration routes and will also help to infer haplogroup background or common ancestry. PMID:22569803

  11. Introducing Human Population Biology through an Easy Laboratory Exercise on Mitochondrial DNA

    ERIC Educational Resources Information Center

    Pardinas, Antonio F.; Dopico, Eduardo; Roca, Agustin; Garcia-Vazquez, Eva; Lopez, Belen

    2010-01-01

    This article describes an easy and cheap laboratory exercise for students to discover their own mitochondrial haplogroup. Students use buccal swabs to obtain mucosa cells as noninvasive tissue samples, extract DNA, and with a simple polymerase chain reaction-restriction fragment length polymorphism analysis they can obtain DNA fragments of…

  12. Mitochondrial genome sequencing in atherosclerosis: what's next?

    PubMed

    Sazonova, Margarita A; Shkurat, Tatiana P; Demakova, Natalya A; Zhelankin, Andrey V; Barinova, Valeria A; Sobenin, Igor A; Orekhov, Alexander N

    2016-01-01

    Cardiovascular diseases are currently a basic cause of mortality in highly developed countries. The major reason for genesis and development of cardiovascular diseases is atherosclerosis. At the present time high technology methods of molecular genetic diagnostics can significantly simplify early presymptomatic recognition of patients with atherosclerosis, to detect risk groups and to perform a family analysis of this pathology. A Next-Generation Sequencing (NGS) technology can be characterized by high productivity and cheapness of full genome analysis of each DNA sample. We suppose that in the nearest future NGS methods will be widely used for scientific and diagnostic purposes, including personalized medicine. In the present review article literature data on using NGS technology were described in studying mitochondrial genome mutations associated with atherosclerosis and its risk factors, such as mitochondrial diabetes, mitochondrial cardiomyopathy, diabetic nephropathy and left ventricular hypertrophy. With the use of the NGS technology it proved to be possible to detect a range of homoplasmic and heteroplasmic mutations and mitochondrial genome haplogroups which are associated with these pathologies. Meanwhile some mutations and haplogroups were detected both in atherosclerosis and in its risk factors. It conveys the suggestion that there are common pathogenetic mechanisms causing these pathologies. What comes next? New paradigm of crosstalk between non-pharmaceutical (including molecular genetic) and true pharmaceutical approaches may be developed to fill the niche of effective and pathogenically targeted pretreatment and treatment of preclinical and subclinical atherosclerosis to avoid the development of chronic life-threatening disease. PMID:26561059

  13. The impact of mitochondrial DNA and nuclear genes related to mitochondrial functioning on the risk of Parkinson's disease.

    PubMed

    Gaweda-Walerych, Katarzyna; Zekanowski, Cezary

    2013-12-01

    Mitochondrial dysfunction and oxidative stress are the major factors implicated in Parkinson's disease (PD) pathogenesis. The maintenance of healthy mitochondria is a very complex process coordinated bi-genomically. Here, we review association studies on mitochondrial haplogroups and subhaplogroups, discussing the underlying molecular mechanisms. We also focus on variation in the nuclear genes (NDUFV2, PGC-1alpha, HSPA9, LRPPRC, MTIF3, POLG1, and TFAM encoding NADH dehydrogenase (ubiquinone) flavoprotein 2, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, mortalin, leucine-rich pentatricopeptide repeat containing protein, translation initiation factor 3, mitochondrial DNA polymerase gamma, and mitochondrial transcription factor A, respectively) primarily linked to regulation of mitochondrial functioning that recently have been associated with PD risk. Possible interactions between mitochondrial and nuclear genetic variants and related proteins are discussed. PMID:24532986

  14. The Impact of Mitochondrial DNA and Nuclear Genes Related to Mitochondrial Functioning on the Risk of Parkinson’s Disease

    PubMed Central

    Gaweda-Walerych, Katarzyna; Zekanowski, Cezary

    2013-01-01

    Mitochondrial dysfunction and oxidative stress are the major factors implicated in Parkinson’s disease (PD) pathogenesis. The maintenance of healthy mitochondria is a very complex process coordinated bi-genomically. Here, we review association studies on mitochondrial haplogroups and subhaplogroups, discussing the underlying molecular mechanisms. We also focus on variation in the nuclear genes (NDUFV2, PGC-1alpha, HSPA9, LRPPRC, MTIF3, POLG1, and TFAM encoding NADH dehydrogenase (ubiquinone) flavoprotein 2, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, mortalin, leucine-rich pentatricopeptide repeat containing protein, translation initiation factor 3, mitochondrial DNA polymerase gamma, and mitochondrial transcription factor A, respectively) primarily linked to regulation of mitochondrial functioning that recently have been associated with PD risk. Possible interactions between mitochondrial and nuclear genetic variants and related proteins are discussed. PMID:24532986

  15. Orthopoxvirus DNA in Eurasian Lynx, Sweden

    PubMed Central

    Okeke, Malachy Ifeanyi; af Segerstad, Carl Hård; Mörner, Torsten; Traavik, Terje; Ryser-Degiorgis, Marie-Pierre

    2011-01-01

    Cowpox virus, which has been used to protect humans against smallpox but may cause severe disease in immunocompromised persons, has reemerged in humans, domestic cats, and other animal species in Europe. Orthopoxvirus (OPV) DNA was detected in tissues (lung, kidney, spleen) in 24 (9%) of 263 free-ranging Eurasian lynx (Lynx lynx) from Sweden. Thymidine kinase gene amplicon sequences (339 bp) from 21 lynx were all identical to those from cowpox virus isolated from a person in Norway and phylogenetically closer to monkeypox virus than to vaccinia virus and isolates from 2 persons with cowpox virus in Sweden. Prevalence was higher among animals from regions with dense, rather than rural, human populations. Lynx are probably exposed to OPV through predation on small mammal reservoir species. We conclude that OPV is widely distributed in Sweden and may represent a threat to humans. Further studies are needed to verify whether this lynx OPV is cowpox virus. PMID:21470451

  16. Northern Eurasian Heat Waves and Droughts

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried; Wang, Hailan; Koster, Randal; Suarez, Max; Groisman, Pavel

    2013-01-01

    This article reviews our understanding of the characteristics and causes of northern Eurasian summertime heat waves and droughts. Additional insights into the nature of temperature and precipitation variability in Eurasia on monthly to decadal time scales and into the causes and predictability of the most extreme events are gained from the latest generation of reanalyses and from supplemental simulations with the NASA GEOS-5 AGCM. Key new results are: 1) the identification of the important role of summertime stationary Rossby waves in the development of the leading patterns of monthly Eurasian surface temperature and precipitation variability (including the development of extreme events such as the 2010 Russian heat wave), 2) an assessment of the mean temperature and precipitation changes that have occurred over northern Eurasia in the last three decades and their connections to decadal variability and global trends in SST, and 3) the quantification (via a case study) of the predictability of the most extreme simulated heat wave/drought events, with some focus on the role of soil moisture in the development and maintenance of such events. A literature survey indicates a general consensus that the future holds an enhanced probability of heat waves across northern Eurasia, while there is less agreement regarding future drought, reflecting a greater uncertainty in soil moisture and precipitation projections. Substantial uncertainties remain in our understanding of heat waves and drought, including the nature of the interactions between the short-term atmospheric variability associated with such extremes and the longer-term variability and trends associated with soil moisture feedbacks, SST anomalies, and an overall warming world.

  17. Mitochondrial Genetic Background Modifies the Relationship between Traffic-Related Air Pollution Exposure and Systemic Biomarkers of Inflammation

    PubMed Central

    Wittkopp, Sharine; Staimer, Norbert; Tjoa, Thomas; Gillen, Daniel; Daher, Nancy; Shafer, Martin; Schauer, James J.; Sioutas, Constantinos; Delfino, Ralph J.

    2013-01-01

    Background Mitochondria are the main source of reactive oxygen species (ROS). Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD). We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. Objective We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production) in this panel (38 subjects and 417 observations). Methods Inflammation biomarkers were measured weekly in each subject (≤12 weeks), including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx), carbon monoxide (CO), organic carbon, elemental and black carbon (EC, BC); and particulate matter mass, three size fractions (<0.25 µm, 0.25–2.5 µm, and 2.5–10 µm in aerodynamic diameter). Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH), and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. Results IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH), and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U. Conclusions Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects. PMID:23717615

  18. The Arabian Cradle: Mitochondrial Relicts of the First Steps along the Southern Route out of Africa

    PubMed Central

    Fernandes, Verónica; Alshamali, Farida; Alves, Marco; Costa, Marta D.; Pereira, Joana B.; Silva, Nuno M.; Cherni, Lotfi; Harich, Nourdin; Cerny, Viktor; Soares, Pedro; Richards, Martin B.; Pereira, Luísa

    2012-01-01

    A major unanswered question regarding the dispersal of modern humans around the world concerns the geographical site of the first human steps outside of Africa. The “southern coastal route” model predicts that the early stages of the dispersal took place when people crossed the Red Sea to southern Arabia, but genetic evidence has hitherto been tenuous. We have addressed this question by analyzing the three minor west-Eurasian haplogroups, N1, N2, and X. These lineages branch directly from the first non-African founder node, the root of haplogroup N, and coalesce to the time of the first successful movement of modern humans out of Africa, ∼60 thousand years (ka) ago. We sequenced complete mtDNA genomes from 85 Southwest Asian samples carrying these haplogroups and compared them with a database of 300 European examples. The results show that these minor haplogroups have a relict distribution that suggests an ancient ancestry within the Arabian Peninsula, and they most likely spread from the Gulf Oasis region toward the Near East and Europe during the pluvial period 55–24 ka ago. This pattern suggests that Arabia was indeed the first staging post in the spread of modern humans around the world. PMID:22284828

  19. [Mitochondrial DNA Polymorphism in Different Populations of Spangled Orloff Chickens].

    PubMed

    Oyuna, N Yu; Moiseyeva, I G; Sevastianova, A A; Vakhrameev, A B; Alexandrov, A V; Kuzevanova, A Yu; Alimov, A A; Sulimova, G E

    2015-09-01

    For the first time, the genetic diversity of the Spangled Orloff chickens was studied by analyzing the polymorphism of the hypervariable region in the D-loop of mitochondrial DNA (mtDNA). Samples for the analysis were collected at the farms ofthe All-Russia Poultry Research and Technological Institute (VNITIP), the All-Russia Institute of Farm Animal Genetics and Breeding (VNIIGRZh), and the Moscow Zoo. The D-loop partial sequences (between nucleotide positions 57 and 523) were determined according to the reference sequence of Gallus gallus spadiceus mtDNA, NC_007235 in 39 individuals obtained from these populations (GenBank Accession Nos. KM391754-KM391792). In the analyzed mtDNA fragment, a total of 20 polymorphic sites localized between positions 167 and 368, as well as at position 446, were described in Spangled Orloff chickens. One polymorphic site at position 221 (haplogroup E, haplotype ORL-2) was unique. All of the identified nucleotide changes were transition-type substitutions. Overall, based on the analysis of poly- morphic sites in the hypervariable fragment of the D-loop of Spangled Orloff chicken mtDNA, we found seven haplotypes belonging to four haplogroups (A, B, C, and E). Haplogroup E (haplotypes ORL-1, ORL-2, and ORL-3) was present in the majority of the studied individual, with the frequencies of 0.77 in the total sample and 0.47 in the VNIIGRZh farm population. Haplogroups A (haplotypes ORL-4 and ORL-7), B (ORL-6), and C (ORL-5) were found only in samples from the VNIIGRZh farm. The studied mtDNA region revealed a lower level of polymorphism in the VNITIP and Moscow Zoo populations, which only had the ORL-1 and ORL-3 haplotypes belonging to Haplogroup E, respectively. Our data suggested that the studied Spangled Orloff chicken populations differed in the composition and frequencies of mtDNA haplogroups and haplotypes. PMID:26606802

  20. Y chromosomal haplogroup J as a signature of the post-neolithic colonization of Europe.

    PubMed

    Di Giacomo, F; Luca, F; Popa, L O; Akar, N; Anagnou, N; Banyko, J; Brdicka, R; Barbujani, G; Papola, F; Ciavarella, G; Cucci, F; Di Stasi, L; Gavrila, L; Kerimova, M G; Kovatchev, D; Kozlov, A I; Loutradis, A; Mandarino, V; Mammi', C; Michalodimitrakis, E N; Paoli, G; Pappa, K I; Pedicini, G; Terrenato, L; Tofanelli, S; Malaspina, P; Novelletto, A

    2004-10-01

    In order to attain a finer reconstruction of the peopling of southern and central-eastern Europe from the Levant, we determined the frequencies of eight lineages internal to the Y chromosomal haplogroup J, defined by biallelic markers, in 22 population samples obtained with a fine-grained sampling scheme. Our results partially resolve a major multifurcation of lineages within the haplogroup. Analyses of molecular variance show that the area covered by haplogroup J dispersal is characterized by a significant degree of molecular radiation for unique event polymorphisms within the haplogroup, with a higher incidence of the most derived sub-haplogroups on the northern Mediterranean coast, from Turkey westward; here, J diversity is not simply a subset of that present in the area in which this haplogroup first originated. Dating estimates, based on simple tandem repeat loci (STR) diversity within each lineage, confirmed the presence of a major population structuring at the time of spread of haplogroup J in Europe and a punctuation in the peopling of this continent in the post-Neolithic, compatible with the expansion of the Greek world. We also present here, for the first time, a novel method for comparative dating of lineages, free of assumptions of STR mutation rates. PMID:15322918

  1. Mitochondrial genomic variation associated with higher mitochondrial copy number: the Cache County Study on Memory Health and Aging

    PubMed Central

    2014-01-01

    Background The mitochondria are essential organelles and are the location of cellular respiration, which is responsible for the majority of ATP production. Each cell contains multiple mitochondria, and each mitochondrion contains multiple copies of its own circular genome. The ratio of mitochondrial genomes to nuclear genomes is referred to as mitochondrial copy number. Decreases in mitochondrial copy number are known to occur in many tissues as people age, and in certain diseases. The regulation of mitochondrial copy number by nuclear genes has been studied extensively. While mitochondrial variation has been associated with longevity and some of the diseases known to have reduced mitochondrial copy number, the role that the mitochondrial genome itself has in regulating mitochondrial copy number remains poorly understood. Results We analyzed the complete mitochondrial genomes from 1007 individuals randomly selected from the Cache County Study on Memory Health and Aging utilizing the inferred evolutionary history of the mitochondrial haplotypes present in our dataset to identify sequence variation and mitochondrial haplotypes associated with changes in mitochondrial copy number. Three variants belonging to mitochondrial haplogroups U5A1 and T2 were significantly associated with higher mitochondrial copy number in our dataset. Conclusions We identified three variants associated with higher mitochondrial copy number and suggest several hypotheses for how these variants influence mitochondrial copy number by interacting with known regulators of mitochondrial copy number. Our results are the first to report sequence variation in the mitochondrial genome that causes changes in mitochondrial copy number. The identification of these variants that increase mtDNA copy number has important implications in understanding the pathological processes that underlie these phenotypes. PMID:25077862

  2. Private Mitochondrial DNA Variants in Danish Patients with Hypertrophic Cardiomyopathy

    PubMed Central

    Hagen, Christian M.; Aidt, Frederik H.; Havndrup, Ole; Hedley, Paula L.; Jensen, Morten K.; Kanters, Jørgen K.; Pham, Tam T.; Bundgaard, Henning; Christiansen, Michael

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM. Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM. In 87 Danish HCM patients, full mtDNA sequencing revealed 446 variants. After elimination of 312 (69.9%) non-coding and synonymous variants, a further 109 (24.4%) with a global prevalence > 0.1%, three (0.7%) haplogroup associated and 19 (2.0%) variants with a low predicted in silico likelihood of pathogenicity, three variants: MT-TC: m.5772G>A, MT-TF: m.644A>G, and MT-CYB: m.15024G>A, p.C93Y remained. A detailed analysis of these variants indicated that none of them are likely to cause HCM. In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM. PMID:25923817

  3. Genetic analysis of seven Italian horse breeds based on mitochondrial DNA D-loop variation.

    PubMed

    Bigi, D; Perrotta, G; Zambonelli, P

    2014-08-01

    To understand the origin and genetic diversity of Italian horses, mitochondrial DNA D-loop sequences were generated for 163 horses from seven breeds. Sequence analysis of a 480-bp segment revealed a total of 84 haplotypes with 57 polymorphic sites, indicating multiple maternal origins and high genetic diversity. Comparison of the haplotypes with the equine mtDNA haplotype/haplogroup nomenclature showed a haplogroup distribution in the Italian breeds more similar to that found in the Middle East breeds than in the European breeds, probably due to the economic and cultural relationship with the Middle East in the past centuries. PMID:24702170

  4. Revisiting the role of the Himalayas in peopling Nepal: insights from mitochondrial genomes.

    PubMed

    Wang, Hua-Wei; Li, Yu-Chun; Sun, Fei; Zhao, Mian; Mitra, Bikash; Chaudhuri, Tapas Kumar; Regmi, Pasupati; Wu, Shi-Fang; Kong, Qing-Peng; Zhang, Ya-Ping

    2012-04-01

    Himalayas was believed to be a formidably geographical barrier between South and East Asia. The observed high frequency of the East Eurasian paternal lineages in Nepal led some researchers to suggest that these lineages were introduced into Nepal from Tibet directly; however, it is also possible that the East Eurasian genetic components might trace their origins to northeast India where abundant East Eurasian maternal lineages have been detected. To trace the origin of the Nepalese maternal genetic components, especially those of East Eurasian ancestry, and then to better understand the role of the Himalayas in peopling Nepal, we have studied the matenal genetic composition extensively, especially the East Eurasian lineages, in Nepalese and its surrounding populations. Our results revealed the closer affinity between the Nepalese and the Tibetans, specifically, the Nepalese lineages of the East Eurasian ancestry generally are phylogenetically closer with the ones from Tibet, albeit a few mitochondrial DNA haplotypes, likely resulted from recent gene flow, were shared between the Nepalese and northeast Indians. It seems that Tibet was most likely to be the homeland for most of the East Eurasian in the Nepalese. Taking into account the previous observation on Y chromosome, now it is convincing that bearer of the East Eurasian genetic components had entered Nepal across the Himalayas around 6 kilo years ago (kya), a scenario in good agreement with the previous results from linguistics and archeology. PMID:22437208

  5. Whole mitochondrial genome genetic diversity in an Estonian population sample.

    PubMed

    Stoljarova, Monika; King, Jonathan L; Takahashi, Maiko; Aaspõllu, Anu; Budowle, Bruce

    2016-01-01

    Mitochondrial DNA is a useful marker for population studies, human identification, and forensic analysis. Commonly used hypervariable regions I and II (HVI/HVII) were reported to contain as little as 25% of mitochondrial DNA variants and therefore the majority of power of discrimination of mitochondrial DNA resides in the coding region. Massively parallel sequencing technology enables entire mitochondrial genome sequencing. In this study, buccal swabs were collected from 114 unrelated Estonians and whole mitochondrial genome sequences were generated using the Illumina MiSeq system. The results are concordant with previous mtDNA control region reports of high haplogroup HV and U frequencies (47.4 and 23.7% in this study, respectively) in the Estonian population. One sample with the Northern Asian haplogroup D was detected. The genetic diversity of the Estonian population sample was estimated to be 99.67 and 95.85%, for mtGenome and HVI/HVII data, respectively. The random match probability for mtGenome data was 1.20 versus 4.99% for HVI/HVII. The nucleotide mean pairwise difference was 27 ± 11 for mtGenome and 7 ± 3 for HVI/HVII data. These data describe the genetic diversity of the Estonian population sample and emphasize the power of discrimination of the entire mitochondrial genome over the hypervariable regions. PMID:26289416

  6. Afghan Hindu Kush: Where Eurasian Sub-Continent Gene Flows Converge

    PubMed Central

    Mazières, Stéphane; Myres, Natalie M.; Lin, Alice A.; Temori, Shah Aga; Metspalu, Mait; Metspalu, Ene; Witzel, Michael; King, Roy J.; Underhill, Peter A.; Villems, Richard; Chiaroni, Jacques

    2013-01-01

    Despite being located at the crossroads of Asia, genetics of the Afghanistan populations have been largely overlooked. It is currently inhabited by five major ethnic populations: Pashtun, Tajik, Hazara, Uzbek and Turkmen. Here we present autosomal from a subset of our samples, mitochondrial and Y- chromosome data from over 500 Afghan samples among these 5 ethnic groups. This Afghan data was supplemented with the same Y-chromosome analyses of samples from Iran, Kyrgyzstan, Mongolia and updated Pakistani samples (HGDP-CEPH). The data presented here was integrated into existing knowledge of pan-Eurasian genetic diversity. The pattern of genetic variation, revealed by structure-like and Principal Component analyses and Analysis of Molecular Variance indicates that the people of Afghanistan are made up of a mosaic of components representing various geographic regions of Eurasian ancestry. The absence of a major Central Asian-specific component indicates that the Hindu Kush, like the gene pool of Central Asian populations in general, is a confluence of gene flows rather than a source of distinctly autochthonous populations that have arisen in situ: a conclusion that is reinforced by the phylogeography of both haploid loci. PMID:24204668

  7. Admixture between historically isolated mitochondrial lineages in captive Western gorillas: recommendations for future management.

    PubMed

    Soto-Calderón, Iván D; Dew, J Larry; Bergl, Richard A; Jensen-Seaman, Michael I; Anthony, Nicola M

    2015-01-01

    Although captive populations of western gorilla have been maintained in the United States for over a century, little is known about the geographic origins and genetic composition of the current zoo population. Furthermore, although previous mitochondrial analyses have shown that free-range gorilla populations exhibit substantial regional differentiation, nothing is known of the extent to which this variation has been preserved in captive populations. To address these questions, we combined 379 pedigree records with data from 52 mitochondrial sequences to infer individual haplogroup affiliations, geographical origin of wild founders and instances of inter-breeding between haplogroups in the United States captive gorilla population. We show that the current captive population contains all major mitochondrial lineages found within wild western lowland gorillas. Levels of haplotype diversity are also comparable to those found in wild populations. However, the majority of captive gorilla matings have occurred between individuals with different haplogroup affiliations. Although restricting crosses to individuals within the same haplogroup would preserve the phylogeographic structure present in the wild, careful management of captive populations is required to minimize the risk of drift and inbreeding. However, when captive animals are released back into the wild, we recommend that efforts should be made to preserve natural phylogeographic structure. PMID:25790828

  8. Admixture Between Historically Isolated Mitochondrial Lineages in Captive Western Gorillas: Recommendations for Future Management

    PubMed Central

    Dew, J. Larry; Bergl, Richard A.; Jensen-Seaman, Michael I.; Anthony, Nicola M.

    2015-01-01

    Although captive populations of western gorilla have been maintained in the United States for over a century, little is known about the geographic origins and genetic composition of the current zoo population. Furthermore, although previous mitochondrial analyses have shown that free-range gorilla populations exhibit substantial regional differentiation, nothing is known of the extent to which this variation has been preserved in captive populations. To address these questions, we combined 379 pedigree records with data from 52 mitochondrial sequences to infer individual haplogroup affiliations, geographical origin of wild founders and instances of inter-breeding between haplogroups in the United States captive gorilla population. We show that the current captive population contains all major mitochondrial lineages found within wild western lowland gorillas. Levels of haplotype diversity are also comparable to those found in wild populations. However, the majority of captive gorilla matings have occurred between individuals with different haplogroup affiliations. Although restricting crosses to individuals within the same haplogroup would preserve the phylogeographic structure present in the wild, careful management of captive populations is required to minimize the risk of drift and inbreeding. However, when captive animals are released back into the wild, we recommend that efforts should be made to preserve natural phylogeographic structure. PMID:25790828

  9. Application of a west Eurasian-specific filter for quasi-median network analysis: Sharpening the blade for mtDNA error detection

    PubMed Central

    Zimmermann, Bettina; Röck, Alexander; Huber, Gabriela; Krämer, Tanja; Schneider, Peter M.; Parson, Walther

    2011-01-01

    The application of quasi-median networks provides an effective tool to check the quality of mtDNA data. Filtering of highly recurrent mutations prior to network analysis is required to simplify the data set and reduce the complexity of the network. The phylogenetic background determines those mutations that need to be filtered. While the traditional EMPOPspeedy filter was based on the worldwide mtDNA phylogeny, haplogroup-specific filters can more effectively highlight potential errors in data of the respective (sub)-continental region. In this study we demonstrate the performance of a new, west Eurasian filter EMPOPspeedyWE for the fine-tuned examination of data sets belonging to macrohaplogroup N that constitutes the main portion of mtDNA lineages in Europe. The effects on the resulting network of different database sizes, high-quality and flawed data, as well as the examination of a phylogenetically distant data set, are presented by examples. The analyses are based on a west Eurasian etalon data set that was carefully compiled from more than 3500 control region sequences for network purposes. Both, etalon data and the new filter file, are provided through the EMPOP database (www.empop.org). PMID:21067984

  10. Chicken domestication: an updated perspective based on mitochondrial genomes

    PubMed Central

    Miao, Y-W; Peng, M-S; Wu, G-S; Ouyang, Y-N; Yang, Z-Y; Yu, N; Liang, J-P; Pianchou, G; Beja-Pereira, A; Mitra, B; Palanichamy, M G; Baig, M; Chaudhuri, T K; Shen, Y-Y; Kong, Q-P; Murphy, R W; Yao, Y-G; Zhang, Y-P

    2013-01-01

    Domestic chickens (Gallus gallus domesticus) fulfill various roles ranging from food and entertainment to religion and ornamentation. To survey its genetic diversity and trace the history of domestication, we investigated a total of 4938 mitochondrial DNA (mtDNA) fragments including 2843 previously published and 2095 de novo units from 2044 domestic chickens and 51 red junglefowl (Gallus gallus). To obtain the highest possible level of molecular resolution, 50 representative samples were further selected for total mtDNA genome sequencing. A fine-gained mtDNA phylogeny was investigated by defining haplogroups A–I and W–Z. Common haplogroups A–G were shared by domestic chickens and red junglefowl. Rare haplogroups H–I and W–Z were specific to domestic chickens and red junglefowl, respectively. We re-evaluated the global mtDNA profiles of chickens. The geographic distribution for each of major haplogroups was examined. Our results revealed new complexities of history in chicken domestication because in the phylogeny lineages from the red junglefowl were mingled with those of the domestic chickens. Several local domestication events in South Asia, Southwest China and Southeast Asia were identified. The assessment of chicken mtDNA data also facilitated our understanding about the Austronesian settlement in the Pacific. PMID:23211792

  11. Chicken domestication: an updated perspective based on mitochondrial genomes.

    PubMed

    Miao, Y-W; Peng, M-S; Wu, G-S; Ouyang, Y-N; Yang, Z-Y; Yu, N; Liang, J-P; Pianchou, G; Beja-Pereira, A; Mitra, B; Palanichamy, M G; Baig, M; Chaudhuri, T K; Shen, Y-Y; Kong, Q-P; Murphy, R W; Yao, Y-G; Zhang, Y-P

    2013-03-01

    Domestic chickens (Gallus gallus domesticus) fulfill various roles ranging from food and entertainment to religion and ornamentation. To survey its genetic diversity and trace the history of domestication, we investigated a total of 4938 mitochondrial DNA (mtDNA) fragments including 2843 previously published and 2095 de novo units from 2044 domestic chickens and 51 red junglefowl (Gallus gallus). To obtain the highest possible level of molecular resolution, 50 representative samples were further selected for total mtDNA genome sequencing. A fine-gained mtDNA phylogeny was investigated by defining haplogroups A-I and W-Z. Common haplogroups A-G were shared by domestic chickens and red junglefowl. Rare haplogroups H-I and W-Z were specific to domestic chickens and red junglefowl, respectively. We re-evaluated the global mtDNA profiles of chickens. The geographic distribution for each of major haplogroups was examined. Our results revealed new complexities of history in chicken domestication because in the phylogeny lineages from the red junglefowl were mingled with those of the domestic chickens. Several local domestication events in South Asia, Southwest China and Southeast Asia were identified. The assessment of chicken mtDNA data also facilitated our understanding about the Austronesian settlement in the Pacific. PMID:23211792

  12. Mitogenomes from Egyptian Cattle Breeds: New Clues on the Origin of Haplogroup Q and the Early Spread of Bos taurus from the Near East

    PubMed Central

    Olivieri, Anna; Gandini, Francesca; Achilli, Alessandro; Fichera, Alessandro; Rizzi, Ermanno; Bonfiglio, Silvia; Battaglia, Vincenza; Brandini, Stefania; De Gaetano, Anna; El-Beltagi, Ahmed; Lancioni, Hovirag; Agha, Saif; Semino, Ornella; Ferretti, Luca; Torroni, Antonio

    2015-01-01

    Background Genetic studies support the scenario that Bos taurus domestication occurred in the Near East during the Neolithic transition about 10 thousand years (ky) ago, with the likely exception of a minor secondary event in Italy. However, despite the proven effectiveness of whole mitochondrial genome data in providing valuable information concerning the origin of taurine cattle, until now no population surveys have been carried out at the level of mitogenomes in local breeds from the Near East or surrounding areas. Egypt is in close geographic and cultural proximity to the Near East, in particular the Nile Delta region, and was one of the first neighboring areas to adopt the Neolithic package. Thus, a survey of mitogenome variation of autochthonous taurine breeds from the Nile Delta region might provide new insights on the early spread of cattle rearing outside the Near East. Methodology Using Illumina high-throughput sequencing we characterized the mitogenomes from two cattle breeds, Menofi (N = 17) and Domiaty (N = 14), from the Nile Delta region. Phylogenetic and Bayesian analyses were subsequently performed. Conclusions Phylogenetic analyses of the 31 mitogenomes confirmed the prevalence of haplogroup T1, similar to most African cattle breeds, but showed also high frequencies for haplogroups T2, T3 and Q1, and an extremely high haplotype diversity, while Bayesian skyline plots pointed to a main episode of population growth ~12.5 ky ago. Comparisons of Nile Delta mitogenomes with those from other geographic areas revealed that (i) most Egyptian mtDNAs are probably direct local derivatives from the founder domestic herds which first arrived from the Near East and the extent of gene flow from and towards the Nile Delta region was limited after the initial founding event(s); (ii) haplogroup Q1 was among these founders, thus proving that it underwent domestication in the Near East together with the founders of the T clades. PMID:26513361

  13. Mitochondrial DNA control region analysis of three ethnic groups in the Republic of Macedonia.

    PubMed

    Jankova-Ajanovska, Renata; Zimmermann, Bettina; Huber, Gabriela; Röck, Alexander W; Bodner, Martin; Jakovski, Zlatko; Janeska, Biljana; Duma, Aleksej; Parson, Walther

    2014-11-01

    A total of 444 individuals representing three ethnic groups (Albanians, Turks and Romanies) in the Republic of Macedonia were sequenced in the mitochondrial control region. The mtDNA haplogroup composition differed between the three groups. Our results showed relatively high frequencies of haplogroup H12 in Albanians (8.8%) and less in Turks (3.3%), while haplogroups M5a1 and H7a1a were dominant in Romanies (13.7% and 10.3%, respectively) but rare in the former two. This highlights the importance of regional sampling for forensic mtDNA databasing purposes. These population data will be available on EMPOP under accession numbers EMP00644 (Albanians), EMP00645 (Romanies) and EMP00646 (Turks). PMID:25051224

  14. DomeTree: a canonical toolkit for mitochondrial DNA analyses in domesticated animals.

    PubMed

    Peng, Min-Sheng; Fan, Long; Shi, Ni-Ni; Ning, Tiao; Yao, Yong-Gang; Murphy, Robert W; Wang, Wen-Zhi; Zhang, Ya-Ping

    2015-09-01

    Mitochondrial DNA (mtDNA) is widely used in various genetic studies of domesticated animals. Many applications require comprehensive knowledge about the phylogeny of mtDNA variants. Herein, we provide the most up-to-date mtDNA phylogeny (i.e. haplogroup tree or matrilineal genealogy) and a standardized hierarchical haplogroup nomenclature system for domesticated cattle, dogs, goats, horses, pigs, sheep, yaks and chickens. These high-resolution mtDNA haplogroup trees based on 1240 complete or near-complete mtDNA genome sequences are available in open resource DomeTree (http://www.dometree.org). In addition, we offer the software MitoToolPy (http://www.mitotool.org/mp.html) to facilitate the mtDNA data analyses. We will continuously and regularly update DomeTree and MitoToolPy. PMID:25655564

  15. Mitochondrial DNA control region analysis of three ethnic groups in the Republic of Macedonia

    PubMed Central

    Jankova-Ajanovska, Renata; Zimmermann, Bettina; Huber, Gabriela; Röck, Alexander W.; Bodner, Martin; Jakovski, Zlatko; Janeska, Biljana; Duma, Aleksej; Parson, Walther

    2014-01-01

    A total of 444 individuals representing three ethnic groups (Albanians, Turks and Romanies) in the Republic of Macedonia were sequenced in the mitochondrial control region. The mtDNA haplogroup composition differed between the three groups. Our results showed relatively high frequencies of haplogroup H12 in Albanians (8.8%) and less in Turks (3.3%), while haplogroups M5a1 and H7a1a were dominant in Romanies (13.7% and 10.3%, respectively) but rare in the former two. This highlights the importance of regional sampling for forensic mtDNA databasing purposes. These population data will be available on EMPOP under accession numbers EMP00644 (Albanians), EMP00645 (Romanies) and EMP00646 (Turks). PMID:25051224

  16. Mitochondrial population genomics supports a single pre-Clovis origin with a coastal route for the peopling of the Americas.

    PubMed

    Fagundes, Nelson J R; Kanitz, Ricardo; Eckert, Roberta; Valls, Ana C S; Bogo, Mauricio R; Salzano, Francisco M; Smith, David Glenn; Silva, Wilson A; Zago, Marco A; Ribeiro-dos-Santos, Andrea K; Santos, Sidney E B; Petzl-Erler, Maria Luiza; Bonatto, Sandro L

    2008-03-01

    It is well accepted that the Americas were the last continents reached by modern humans, most likely through Beringia. However, the precise time and mode of the colonization of the New World remain hotly disputed issues. Native American populations exhibit almost exclusively five mitochondrial DNA (mtDNA) haplogroups (A-D and X). Haplogroups A-D are also frequent in Asia, suggesting a northeastern Asian origin of these lineages. However, the differential pattern of distribution and frequency of haplogroup X led some to suggest that it may represent an independent migration to the Americas. Here we show, by using 86 complete mitochondrial genomes, that all Native American haplogroups, including haplogroup X, were part of a single founding population, thereby refuting multiple-migration models. A detailed demographic history of the mtDNA sequences estimated with a Bayesian coalescent method indicates a complex model for the peopling of the Americas, in which the initial differentiation from Asian populations ended with a moderate bottleneck in Beringia during the last glacial maximum (LGM), around approximately 23,000 to approximately 19,000 years ago. Toward the end of the LGM, a strong population expansion started approximately 18,000 and finished approximately 15,000 years ago. These results support a pre-Clovis occupation of the New World, suggesting a rapid settlement of the continent along a Pacific coastal route. PMID:18313026

  17. Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt-Jakob disease.

    PubMed

    Zhang, Jin; Zhang, Zhi-Xia; Du, Peng-Chen; Zhou, Wei; Wu, Su-Dong; Wang, Qi-Ling; Chen, Cao; Shi, Qi; Chen, Chen; Gao, Chen; Tian, Chan; Dong, Xiao-Ping

    2015-01-01

    Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt-Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (P<0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu) were detected in sCJD. The frequencies of two synonymous amino-acid changes, m.11467A>G, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations. PMID:24667788

  18. Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt–Jakob disease

    PubMed Central

    Zhang, Jin; Zhang, Zhi-Xia; Du, Peng-Chen; Zhou, Wei; Wu, Su-Dong; Wang, Qi-Ling; Chen, Cao; Shi, Qi; Chen, Chen; Gao, Chen; Tian, Chan; Dong, Xiao-Ping

    2015-01-01

    Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt–Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (P<0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu) were detected in sCJD. The frequencies of two synonymous amino-acid changes, m.11467A>G, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations. PMID:24667788

  19. Haplotype diversity in mitochondrial DNA hypervariable region in a population of southeastern Brazil.

    PubMed

    Fridman, C; Gonzalez, R S; Pereira, A C; Cardena, M M S G

    2014-07-01

    Brazilian population derives from Native Amerindians, Europeans, and Africans. Southeastern Brazil is the most populous region of the country. The present study intended to characterize the maternal genetic ancestry of 290 individuals from southeastern (Brazil) population. Thus, we made the sequencing of the three hypervariable regions (HV1, HV2, and HV3) of the mitochondrial DNA (mtDNA). The statistical analyses were made using Arlequin software, and the median-joining haplotype networks were generated using Network software. The analysis of three hypervariable regios showed 230 (79.3 %) unique haplotypes and the most common haplotype was "263G" carried by 12 (4.1 %) individuals. The strikingly high variability generated by intense gene flow is mirrored in a high sequence diversity (0.9966 ± 0.0010), and the probability of two random individuals showing identical mtDNA haplotypes were 0.0068. The analysis of haplogroup distribution revealed that 36.9 % (n = 107) presented Amerindian haplogroups, 35.2 % (n = 102) presented African haplogroups, 27.6 % (n = 80) presented European haplogroups, and one (0.3 %) individual presented East Asian haplogroup, evidencing that the southeastern population is extremely heterogeneous and the coexistence of matrilineal lineages with three different phylogeographic origins. The genetic diversity found in the mtDNA control region in the southeastern Brazilian population reinforces the importance of increased national database in order to be important and informative in forensic cases. PMID:24846100

  20. Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes.

    PubMed

    Atilano, Shari R; Malik, Deepika; Chwa, Marilyn; Cáceres-Del-Carpio, Javier; Nesburn, Anthony B; Boyer, David S; Kuppermann, Baruch D; Jazwinski, S Michal; Miceli, Michael V; Wallace, Douglas C; Udar, Nitin; Kenney, M Cristina

    2015-08-15

    Mitochondrial (mt) DNA can be classified into haplogroups representing different geographic and/or racial origins of populations. The H haplogroup is protective against age-related macular degeneration (AMD), while the J haplogroup is high risk for AMD. In the present study, we performed comparison analyses of human retinal cell cybrids, which possess identical nuclei, but mtDNA from subjects with either the H or J haplogroups, and demonstrate differences in total global methylation, and expression patterns for two genes related to acetylation and five genes related to methylation. Analyses revealed that untreated-H and -J cybrids have different expression levels for nuclear genes (CFH, EFEMP1, VEGFA and NFkB2). However, expression levels for these genes become equivalent after treatment with a methylation inhibitor, 5-aza-2'-deoxycytidine. Moreover, sequencing of the entire mtDNA suggests that differences in epigenetic status found in cybrids are likely due to single nucleotide polymorphisms (SNPs) within the haplogroup profiles rather than rare variants or private SNPs. In conclusion, our findings indicate that mtDNA variants can mediate methylation profiles and transcription for inflammation, angiogenesis and various signaling pathways, which are important in several common diseases. PMID:25964427

  1. Distinguishing the co-ancestries of haplogroup G Y-chromosomes in the populations of Europe and the Caucasus

    PubMed Central

    Rootsi, Siiri; Myres, Natalie M; Lin, Alice A; Järve, Mari; King, Roy J; Kutuev, Ildus; Cabrera, Vicente M; Khusnutdinova, Elza K; Varendi, Kärt; Sahakyan, Hovhannes; Behar, Doron M; Khusainova, Rita; Balanovsky, Oleg; Balanovska, Elena; Rudan, Pavao; Yepiskoposyan, Levon; Bahmanimehr, Ardeshir; Farjadian, Shirin; Kushniarevich, Alena; Herrera, Rene J; Grugni, Viola; Battaglia, Vincenza; Nici, Carmela; Crobu, Francesca; Karachanak, Sena; Kashani, Baharak Hooshiar; Houshmand, Massoud; Sanati, Mohammad H; Toncheva, Draga; Lisa, Antonella; Semino, Ornella; Chiaroni, Jacques; Cristofaro, Julie Di; Villems, Richard; Kivisild, Toomas; Underhill, Peter A

    2012-01-01

    Haplogroup G, together with J2 clades, has been associated with the spread of agriculture, especially in the European context. However, interpretations based on simple haplogroup frequency clines do not recognize underlying patterns of genetic diversification. Although progress has been recently made in resolving the haplogroup G phylogeny, a comprehensive survey of the geographic distribution patterns of the significant sub-clades of this haplogroup has not been conducted yet. Here we present the haplogroup frequency distribution and STR variation of 16 informative G sub-clades by evaluating 1472 haplogroup G chromosomes belonging to 98 populations ranging from Europe to Pakistan. Although no basal G-M201* chromosomes were detected in our data set, the homeland of this haplogroup has been estimated to be somewhere nearby eastern Anatolia, Armenia or western Iran, the only areas characterized by the co-presence of deep basal branches as well as the occurrence of high sub-haplogroup diversity. The P303 SNP defines the most frequent and widespread G sub-haplogroup. However, its sub-clades have more localized distribution with the U1-defined branch largely restricted to Near/Middle Eastern and the Caucasus, whereas L497 lineages essentially occur in Europe where they likely originated. In contrast, the only U1 representative in Europe is the G-M527 lineage whose distribution pattern is consistent with regions of Greek colonization. No clinal patterns were detected suggesting that the distributions are rather indicative of isolation by distance and demographic complexities. PMID:22588667

  2. Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression

    PubMed Central

    Hendrickson, Sher L.; Lautenberger, James A.; Chinn, Leslie Wei; Malasky, Michael; Sezgin, Efe; Kingsley, Lawrence A.; Goedert, James J.; Kirk, Gregory D.; Gomperts, Edward D.; Buchbinder, Susan P.; Troyer, Jennifer L.; O'Brien, Stephen J.

    2010-01-01

    Background The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression. Methodology/Principal Findings Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl-CoA isomerase (PECI) on chromosome 6. Conclusions Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclear-encoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis. PMID:20877624

  3. Mitochondrial genotype in vulvar carcinoma - cuckoo in the nest

    PubMed Central

    2010-01-01

    Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection. PMID:20825678

  4. Implications of hybridization, NUMTs, and overlooked diversity for DNA Barcoding of Eurasian ground squirrels.

    PubMed

    Ermakov, Oleg A; Simonov, Evgeniy; Surin, Vadim L; Titov, Sergey V; Brandler, Oleg V; Ivanova, Natalia V; Borisenko, Alex V

    2015-01-01

    The utility of DNA Barcoding for species identification and discovery has catalyzed a concerted effort to build the global reference library; however, many animal groups of economical or conservational importance remain poorly represented. This study aims to contribute DNA barcode records for all ground squirrel species (Xerinae, Sciuridae, Rodentia) inhabiting Eurasia and to test efficiency of this approach for species discrimination. Cytochrome c oxidase subunit 1 (COI) gene sequences were obtained for 97 individuals representing 16 ground squirrel species of which 12 were correctly identified. Taxonomic allocation of some specimens within four species was complicated by geographically restricted mtDNA introgression. Exclusion of individuals with introgressed mtDNA allowed reaching a 91.6% identification success rate. Significant COI divergence (3.5-4.4%) was observed within the most widespread ground squirrel species (Spermophilus erythrogenys, S. pygmaeus, S. suslicus, Urocitellus undulatus), suggesting the presence of cryptic species. A single putative NUMT (nuclear mitochondrial pseudogene) sequence was recovered during molecular analysis; mitochondrial COI from this sample was amplified following re-extraction of DNA. Our data show high discrimination ability of 100 bp COI fragments for Eurasian ground squirrels (84.3%) with no incorrect assessments, underscoring the potential utility of the existing reference librariy for the development of diagnostic 'mini-barcodes'. PMID:25617768

  5. Implications of Hybridization, NUMTs, and Overlooked Diversity for DNA Barcoding of Eurasian Ground Squirrels

    PubMed Central

    Ermakov, Oleg A.; Simonov, Evgeniy; Surin, Vadim L.; Titov, Sergey V.; Brandler, Oleg V.; Ivanova, Natalia V.; Borisenko, Alex V.

    2015-01-01

    The utility of DNA Barcoding for species identification and discovery has catalyzed a concerted effort to build the global reference library; however, many animal groups of economical or conservational importance remain poorly represented. This study aims to contribute DNA barcode records for all ground squirrel species (Xerinae, Sciuridae, Rodentia) inhabiting Eurasia and to test efficiency of this approach for species discrimination. Cytochrome c oxidase subunit 1 (COI) gene sequences were obtained for 97 individuals representing 16 ground squirrel species of which 12 were correctly identified. Taxonomic allocation of some specimens within four species was complicated by geographically restricted mtDNA introgression. Exclusion of individuals with introgressed mtDNA allowed reaching a 91.6% identification success rate. Significant COI divergence (3.5–4.4%) was observed within the most widespread ground squirrel species (Spermophilus erythrogenys, S. pygmaeus, S. suslicus, Urocitellus undulatus), suggesting the presence of cryptic species. A single putative NUMT (nuclear mitochondrial pseudogene) sequence was recovered during molecular analysis; mitochondrial COI from this sample was amplified following re-extraction of DNA. Our data show high discrimination ability of 100 bp COI fragments for Eurasian ground squirrels (84.3%) with no incorrect assessments, underscoring the potential utility of the existing reference librariy for the development of diagnostic ‘mini-barcodes’. PMID:25617768

  6. Mitochondrial-Nuclear Epistasis: Implications for Human Aging and Longevity

    PubMed Central

    Tranah, Gregory

    2010-01-01

    There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. A diversity of pathways may influence the way mitochondria and nuclear – mitochondrial interactions modulate longevity, including: oxidative phosphorylation; mitochondrial uncoupling; antioxidant defenses; mitochondrial fission and fusion; and sirtuin regulation of mitochondrial genes. We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability. PMID:20601194

  7. Y-chromosome E haplogroups: their distribution and implication to the origin of Afro-Asiatic languages and pastoralism

    PubMed Central

    Gebremeskel, Eyoab I; Ibrahim, Muntaser E

    2014-01-01

    Archeological and paleontological evidences point to East Africa as the likely area of early evolution of modern humans. Genetic studies also indicate that populations from the region often contain, but not exclusively, representatives of the more basal clades of mitochondrial and Y-chromosome phylogenies. Most Y-chromosome haplogroup diversity in Africa, however, is present within macrohaplogroup E that seem to have appeared 21 000–32 000 YBP somewhere between the Red Sea and Lake Chad. The combined analysis of 17 bi-allelic markers in 1214 Y chromosomes together with cultural background of 49 populations displayed in various metrics: network, multidimensional scaling, principal component analysis and neighbor-joining plots, indicate a major contribution of East African populations to the foundation of the macrohaplogroup, suggesting a diversification that predates the appearance of some cultural traits and the subsequent expansion that is more associated with the cultural and linguistic diversity witnessed today. The proto-Afro-Asiatic group carrying the E-P2 mutation may have appeared at this point in time and subsequently gave rise to the different major population groups including current speakers of the Afro-Asiatic languages and pastoralist populations. PMID:24667790

  8. Mitochondrial DNA variation and the origins of the Aleuts.

    PubMed

    Rubicz, Rohina; Schurr, Theodore G; Babb, Paul L; Crawford, Michael H

    2003-12-01

    The mitochondrial DNA (mtDNA) variation in 179 Aleuts from five different islands (Atka, Unalaska, Umnak, St. Paul, and St. George) and Anchorage was analyzed to better understand the origins of Aleuts and their role in the peopling of the Americas. Mitochondrial DNA samples were characterized using polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing of the first hypervariable segment (HVS-I) of the control region. This study showed that Aleut mtDNAs belonged to two of the four haplogroups (A and D) common among Native Americans. Haplogroup D occurred at a very high frequency in Aleuts, and this, along with their unique HVS-I sequences, distinguished them from Eskimos, Athapaskan Indians, and other northern Amerindian populations. While sharing several control region sequences (CIR11, CHU14, CIR60, and CIR61) with other circumarctic populations, Aleuts lacked haplogroup A mtDNAs having the 16265G mutation that are specific to Eskimo populations. R-matrix and median network analyses indicated that Aleuts were closest genetically to Chukotkan (Chukchi and Siberian Eskimos) rather than to Native American or Kamchatkan populations (Koryaks and Itel'men). Dating of the Beringian branch of haplogroup A (16192T) suggested that populations ancestral to the Aleuts, Eskimos, and Athapaskan Indians emerged approximately 13,120 years ago, while Aleut-specific A and D sublineages were dated at 6539 +/- 3511 and 6035 +/- 2885 years, respectively. Our findings support the archaeologically based hypothesis that ancestral Aleuts crossed the Bering Land Bridge or Beringian platform and entered the Aleutian Islands from the east, rather than island hopping from Kamchatka into the western Aleutians. Furthermore, the Aleut migration most likely represents a separate event from those responsible for peopling the remainder of the Americas, meaning that the New World was colonized through multiple migrations. PMID:15018033

  9. Understanding Higher Education Admissions Reforms in the Eurasian Context

    ERIC Educational Resources Information Center

    Drummond, Todd W.; Gabrscek, Sergij

    2012-01-01

    In the twenty years since independence, new Eurasian nation-states of the former Soviet Union have introduced major changes to the way students are admitted to institutions of higher education. Azerbaijan (1992), Uzbekistan (1993), Kazakhstan (1999), Russia (2001), Kyrgyzstan (2002), Ukraine (2004), and Georgia (2005) have all created new state or…

  10. Winter Eurasian Climate Variability: Role of Cyclone and Anticyclone Activity

    NASA Astrophysics Data System (ADS)

    Lu, C.; Zhang, X.; Guan, Z.

    2012-12-01

    This study investigates variability of extratropical Eurasian cyclone and anticyclone activity by using a modified automated cyclone and anticyclone identification and tracking algorithm. The cyclone and anticyclone activities are quantified by their regionally integrated intensity (CI and ACI) during 1978/79-2011/2012 winter seasons. We found that the time evolutions of the CI and ACI exhibit a general negative correlation of -0.7 between them at a significant level of 99.99%. This anticyclone (cyclone) variability contributes to the substantially large-scale sea level pressure variability over extratropical Eurasian continent, and explains the interannual fluctuation of surface air temperature over mid latitude Eurasia as well as the adjacent continents. The ACI swings from one phase to another, also producing large changes in snow cover extend, snow equivalent water as well as frequency of extreme cold events over the Eurasian continent. The strengthening of anticyclone intensity is preceded by retreated of the October sea-ice extent over Barents-Kara Sea, which associates tightly with an increasing stability at lower troposphere around the Ural Mountains and induces strengthening Eurasian anticyclones activity in the subsequent winter.

  11. 76 FR 25302 - Executive-Led Eurasian Trade Mission

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE International Trade Administration Executive-Led Eurasian Trade Mission AGENCY: International Trade Administration, Commerce. ACTION: Update. Mission Description The United States Department of Commerce, International Trade Administration, U.S....

  12. New binary polymorphisms reshape and increase resolution of the human Y chromosomal haplogroup tree

    PubMed Central

    Karafet, Tatiana M.; Mendez, Fernando L.; Meilerman, Monica B.; Underhill, Peter A.; Zegura, Stephen L.; Hammer, Michael F.

    2008-01-01

    Markers on the non-recombining portion of the human Y chromosome continue to have applications in many fields including evolutionary biology, forensics, medical genetics, and genealogical reconstruction. In 2002, the Y Chromosome Consortium published a single parsimony tree showing the relationships among 153 haplogroups based on 243 binary markers and devised a standardized nomenclature system to name lineages nested within this tree. Here we present an extensively revised Y chromosome tree containing 311 distinct haplogroups, including two new major haplogroups (S and T), and incorporating approximately 600 binary markers. We describe major changes in the topology of the parsimony tree and provide names for new and rearranged lineages within the tree following the rules presented by the Y Chromosome Consortium in 2002. Several changes in the tree topology have important implications for studies of human ancestry. We also present demography-independent age estimates for 11 of the major clades in the new Y chromosome tree. PMID:18385274

  13. Antennal phenotype of Mexican haplogroups of the Triatoma dimidiata complex, vectors of Chagas disease.

    PubMed

    May-Concha, Irving; Guerenstein, Pablo G; Ramsey, Janine M; Rojas, Julio C; Catalá, Silvia

    2016-06-01

    Triatoma dimidiata (Latreille) is a species complex that spans North, Central, and South America and which is a key vector of all known discrete typing units (DTU) of Trypanosoma cruzi, the etiologic agent of Chagas disease. Morphological and genetic studies indicate that T. dimidiata is a species complex with three principal haplogroups (hg) in Mexico. Different markers and traits are still inconclusive regarding if other morphological differentiation may indicate probable behavioral and vectorial divergences within this complex. In this paper we compared the antennae of three Mexican haplogroups (previously verified by molecular markers ND4 and ITS-2) and discussed possible relationships with their capacity to disperse and colonized new habitats. The abundance of each type of sensillum (bristles, basiconics, thick- and thin-walled trichoids) on the antennae of the three haplogroups, were measured under light microscopy and compared using Kruskal-Wallis non-parametric and multivariate non-parametric analyses. Discriminant analyses indicate significant differences among the antennal phenotype of haplogroups either for adults and some nymphal stages, indicating consistency of the character to analyze intraspecific variability within the complex. The present study shows that the adult antennal pedicel of the T. dimidiata complex have abundant chemosensory sensilla, according with good capacity for dispersal and invasion of different habitats also related to their high capacity to adapt to conserved as well as modified habitats. However, the numerical differences among the haplogroups are suggesting variations in that capacity. The results here presented support the evidence of T. dimidiata as a species complex but show females and males in a different way. Given the close link between the bug's sensory system and its habitat and host-seeking behavior, AP characterization could be useful to complement genetic, neurological and ethological studies of the closely

  14. A European Mitochondrial Haplotype Identified in Ancient Phoenician Remains from Carthage, North Africa.

    PubMed

    Matisoo-Smith, Elizabeth A; Gosling, Anna L; Boocock, James; Kardailsky, Olga; Kurumilian, Yara; Roudesli-Chebbi, Sihem; Badre, Leila; Morel, Jean-Paul; Sebaï, Leïla Ladjimi; Zalloua, Pierre A

    2016-01-01

    While Phoenician culture and trade networks had a significant impact on Western civilizations, we know little about the Phoenicians themselves. In 1994, a Punic burial crypt was discovered on Byrsa Hill, near the entry to the National Museum of Carthage in Tunisia. Inside this crypt were the remains of a young man along with a range of burial goods, all dating to the late 6th century BCE. Here we describe the complete mitochondrial genome recovered from the Young Man of Byrsa and identify that he carried a rare European haplogroup, likely linking his maternal ancestry to Phoenician influenced locations somewhere on the North Mediterranean coast, the islands of the Mediterranean or the Iberian Peninsula. This result not only provides the first direct ancient DNA evidence of a Phoenician individual but the earliest evidence of a European mitochondrial haplogroup, U5b2c1, in North Africa. PMID:27224451

  15. A European Mitochondrial Haplotype Identified in Ancient Phoenician Remains from Carthage, North Africa

    PubMed Central

    Matisoo-Smith, Elizabeth A.; Gosling, Anna L.; Boocock, James; Kardailsky, Olga; Kurumilian, Yara; Roudesli-Chebbi, Sihem; Badre, Leila; Morel, Jean-Paul; Sebaï, Leïla Ladjimi; Zalloua, Pierre A.

    2016-01-01

    While Phoenician culture and trade networks had a significant impact on Western civilizations, we know little about the Phoenicians themselves. In 1994, a Punic burial crypt was discovered on Byrsa Hill, near the entry to the National Museum of Carthage in Tunisia. Inside this crypt were the remains of a young man along with a range of burial goods, all dating to the late 6th century BCE. Here we describe the complete mitochondrial genome recovered from the Young Man of Byrsa and identify that he carried a rare European haplogroup, likely linking his maternal ancestry to Phoenician influenced locations somewhere on the North Mediterranean coast, the islands of the Mediterranean or the Iberian Peninsula. This result not only provides the first direct ancient DNA evidence of a Phoenician individual but the earliest evidence of a European mitochondrial haplogroup, U5b2c1, in North Africa. PMID:27224451

  16. Pan-Eurasian experiment (PEEX) establishing a process towards high level Pan-Eurasian atmosphere-ecosystem observation networks

    NASA Astrophysics Data System (ADS)

    Lappalainen, Hanna K.; Petäjä, Tuukka; Zaytzeva, Nina; Viisanen, Yrjö; Kotlyakov, Vladimir; Kasimov, Nikolay; Bondur, Valery; Matvienko, Gennady; Zilitinkevich, Sergej; Kulmala, Markku

    2014-05-01

    Pan-Eurasian Experiment (PEEX) is a new multidisciplinary research approach aiming at resolving the major uncertainties in the Earth system science and global sustainability questions in the Arctic and boreal Pan-Eurasian regions (Kulmala et al. 2011). The main goal of PEEX Research agenda is to contribute to solving the scientific questions that are specifically important for the Pan-Eurasian region in the coming years, in particular the global climate change and its consequences to nature and human society. Pan Eurasian region represents one the Earth most extensive areas of boreal forest (taiga) and the largest natural wetlands, thus being a significant source area of trace gas emissions, biogenic aerosol particles, and source and sink area for the greenhouse gas (GHG) exchange in a global scale (Guenther et al. 1995, Timkovsky et al. 2010, Tunved et al. 2006, Glagolev et al. 2010). One of the first activities of the PEEX initiative is to establish a process towards high level Pan-Eurasian Observation Networks. Siberian region is currently lacking a coordinated, coherent ground based atmosphere-ecosystem measurement network, which would be crucial component for observing and predicting the effects of climate change in the Northern Pan- Eurasian region The vision of the Pan-Eurasion network will be based on a hierarchical SMEAR-type (Stations Measuring Atmosphere-Ecosystem Interactions) integrated land-atmosphere observation system (Hari et al. 2009). A suite of stations have been selected for the Preliminary Phase of PEEX Observation network. These Preliminary Phase stations includes the SMEAR-type stations in Finland (SMEAR-I-II-II-IV stations), in Estonia (SMEAR-Järviselja) and in China (SMEAR-Nanjing) and selected stations in Russia and ecosystem station network in China. PEEX observation network will fill in the current observational gap in the Siberian region and bring the Siberian observation setup into international context with the with standardized or

  17. Mitochondrial complex 1 gene analysis in keratoconus

    PubMed Central

    Pathak, Dhananjay; Nayak, Bhagabat; Singh, Manvendra; Sharma, Namrata; Tandon, Radhika; Sinha, Rajesh; Titiyal, Jeewan S.

    2011-01-01

    Purpose Keratoconus is characterized by the thinning of corneal stroma, resulting in reduced vision. The exact etiology of keratoconus (KC) is still unknown. The involvement of oxidative stress (OS) in this disease has been reported. However, the exact mechanism of OS in keratoconus is still unknown. Thus we planned this study to screen mitochondrial complex I genes for sequence changes in keratoconus patients and controls, as mitochondrial complex I is the chief source of reactive oxygen species (ROS) production. Methods A total of 20 keratoconus cases and 20 healthy controls without any ocular disorder were enrolled in this study. Mitochondrial complex I genes (ND1, 2, 3, 4, 4L, 5, and 6) were amplified in all patients and controls using 12 pairs of primers by PCR. After sequencing, DNA sequences were analyzed against the mitochondrial reference sequence NC_012920. Haplogroup frequency based Principle Component Analysis (PCA) was constructed to determine whether the gene pool of keratoconus patients is closer to major populations in India. Results DNA sequencing revealed a total 84 nucleotide variations in patients and 29 in controls. Of 84 nucleotide changes, 18 variations were non-synonymous and two novel frame-shift mutations were detected in cases. Non-synonymous mtDNA sequence variations may account for increased ROS and decreased ATP production. This ultimately leads to OS; which is a known cause for variety of corneal abnormalities. Haplotype analysis showed that most of the patients were clustered under the haplogroups: T, C4a2a, R2’TJ, M21’Q1a, M12’G2a2a, M8’CZ and M7a2a, which are present as negligible frequency in normal Indian population, whereas only few patients were found to be a part of the other haplogroups like U7 (Indo-European), R2 and R31, whose origin is contentious. Conclusions Mt complex I sequence variations are the main cause of elevated ROS production which leads oxidative stress. This oxidative stress then starts a cascade of

  18. Population data of mitochondrial DNA HVS-I and HVS-II sequences for 208 Henan Han Chinese.

    PubMed

    Xu, Kaikai; Hu, Shengping

    2015-07-01

    The two hypervariable segments (HVS-I and HVS-II) of mitochondrial DNA (mtDNA) control region were sequenced for a population of 208 unrelated healthy individuals sampled from Suiping County, Henan Province, China. A total of 192 different haplotypes were identified, of which 179 haplotypes were unique (93.23%). The variation of the mtDNA HVS-I and HVS-II was confined to 166 nucleotide positions, of which 115 were observed in the HVS-I and 51 in the HVS-II. The haplotype diversity and random match probability were 0.9991 and 0.0061, respectively. Following the principle of the updated East Asian mtDNA phylogeny tree, individual samples were assigned to the specific haplogroups based on the information both from control region and coding-region obtained. Haplogroup D was the most common haplogroup (25.96%). The northern China-prevalent haplogroups (A, C, D, G, M8, Y, and Z) and the southern China-prevalent haplogroups (B, F, M7, N9, and R9) accounted for 48.56% and 46.63%, respectively, of the Henan Han mtDNA gene pool. The mtDNA hypervariable region was highly polymorphic in Henan Han population. These sequences could serve as mtDNA reference data for forensic casework in Henan population as well as for population genetic study. PMID:25759193

  19. Mitochondrial DNA variants in obesity.

    PubMed

    Knoll, Nadja; Jarick, Ivonne; Volckmar, Anna-Lena; Klingenspor, Martin; Illig, Thomas; Grallert, Harald; Gieger, Christian; Wichmann, Heinz-Erich; Peters, Annette; Wiegand, Susanna; Biebermann, Heike; Fischer-Posovszky, Pamela; Wabitsch, Martin; Völzke, Henry; Nauck, Matthias; Teumer, Alexander; Rosskopf, Dieter; Rimmbach, Christian; Schreiber, Stefan; Jacobs, Gunnar; Lieb, Wolfgang; Franke, Andre; Hebebrand, Johannes; Hinney, Anke

    2014-01-01

    Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI ≥ 30 kg/m2) and n = 2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and their

  20. Mitochondrial DNA Variants in Obesity

    PubMed Central

    Knoll, Nadja; Jarick, Ivonne; Volckmar, Anna-Lena; Klingenspor, Martin; Illig, Thomas; Grallert, Harald; Gieger, Christian; Wichmann, Heinz-Erich; Peters, Annette; Wiegand, Susanna; Biebermann, Heike; Fischer-Posovszky, Pamela; Wabitsch, Martin; Völzke, Henry; Nauck, Matthias; Teumer, Alexander; Rosskopf, Dieter; Rimmbach, Christian; Schreiber, Stefan; Jacobs, Gunnar; Lieb, Wolfgang; Franke, Andre; Hebebrand, Johannes; Hinney, Anke

    2014-01-01

    Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI≥30 kg/m2) and n = 2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between

  1. The Multifaceted Origin of Taurine Cattle Reflected by the Mitochondrial Genome

    PubMed Central

    Olivieri, Anna; Malusà, Arianna; Pala, Maria; Kashani, Baharak Hooshiar; Perego, Ugo A.; Ajmone-Marsan, Paolo; Liotta, Luigi; Semino, Ornella; Bandelt, Hans-Jürgen; Ferretti, Luca; Torroni, Antonio

    2009-01-01

    A Neolithic domestication of taurine cattle in the Fertile Crescent from local aurochsen (Bos primigenius) is generally accepted, but a genetic contribution from European aurochsen has been proposed. Here we performed a survey of a large number of taurine cattle mitochondrial DNA (mtDNA) control regions from numerous European breeds confirming the overall clustering within haplogroups (T1, T2 and T3) of Near Eastern ancestry, but also identifying eight mtDNAs (1.3%) that did not fit in haplogroup T. Sequencing of the entire mitochondrial genome showed that four mtDNAs formed a novel branch (haplogroup R) which, after the deep bifurcation that gave rise to the taurine and zebuine lineages, constitutes the earliest known split in the mtDNA phylogeny of B. primigenius. The remaining four mtDNAs were members of the recently discovered haplogroup Q. Phylogeographic data indicate that R mtDNAs were derived from female European aurochsen, possibly in the Italian Peninsula, and sporadically included in domestic herds. In contrast, the available data suggest that Q mtDNAs and T subclades were involved in the same Neolithic event of domestication in the Near East. Thus, the existence of novel (and rare) taurine haplogroups highlights a multifaceted genetic legacy from distinct B. primigenius populations. Taking into account that the maternally transmitted mtDNA tends to underestimate the extent of gene flow from European aurochsen, the detection of the R mtDNAs in autochthonous breeds, some of which are endangered, identifies an unexpected reservoir of genetic variation that should be carefully preserved. PMID:19484124

  2. The phylogenetic and geographic structure of Y-chromosome haplogroup R1a

    PubMed Central

    Underhill, Peter A; Poznik, G David; Rootsi, Siiri; Järve, Mari; Lin, Alice A; Wang, Jianbin; Passarelli, Ben; Kanbar, Jad; Myres, Natalie M; King, Roy J; Di Cristofaro, Julie; Sahakyan, Hovhannes; Behar, Doron M; Kushniarevich, Alena; Šarac, Jelena; Šaric, Tena; Rudan, Pavao; Pathak, Ajai Kumar; Chaubey, Gyaneshwer; Grugni, Viola; Semino, Ornella; Yepiskoposyan, Levon; Bahmanimehr, Ardeshir; Farjadian, Shirin; Balanovsky, Oleg; Khusnutdinova, Elza K; Herrera, Rene J; Chiaroni, Jacques; Bustamante, Carlos D; Quake, Stephen R; Kivisild, Toomas; Villems, Richard

    2015-01-01

    R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25 000 (95% CI: 21 300–29 000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800–6800) years. The spatial frequency distributions of R1a sub-haplogroups conclusively indicate two major groups, one found primarily in Europe and the other confined to Central and South Asia. Beyond the major European versus Asian dichotomy, we describe several younger sub-haplogroups. Based on spatial distributions and diversity patterns within the R1a-M420 clade, particularly rare basal branches detected primarily within Iran and eastern Turkey, we conclude that the initial episodes of haplogroup R1a diversification likely occurred in the vicinity of present-day Iran. PMID:24667786

  3. Trichomonosis in Eurasian sparrowhawks in the Czech Republic.

    PubMed

    Kunca, Tomas; Smejkalova, Pavla; Cepicka, Ivan

    2015-01-01

    Pigeon, doves and songbirds are hosts of the parasite Trichomonas gallinae (Rivolta, 1878), which causes avian trichomonosis. Raptors are infected when they digest infected prey. A high percentage of the diet of Eurasian sparrowhawk Accipiter nisus (Linnaeus) is comprised of birds. During the breeding season 2012 and 2013, we clinically tested 298 nestling Eurasian sparrowhawks from urban and rural areas of the Czech Republic for the presence of trichomonads. Sparrowhawk nestlings in the urban area were more infected (32.9%) than in the rural area (12.2%) in 2012 (χ(2) = 6.184, P = 0.045). The number of infected nestlings dropped in the urban area (5.4%) and remained similar in the rural area (16.6%) in 2013. Sequences of ITS region and SSU rDNA confirmed that the isolates from infected sparrowhawk nestlings belonged to Trichomonas gallinae. PMID:26198549

  4. Upper mantle flow and lithospheric dynamics beneath the Eurasian region

    NASA Astrophysics Data System (ADS)

    Zhang, G.; Jiang, G.; Jia, Z.; Gao, R.; Fu, R.

    2010-12-01

    Evidence from seismic tomography, geothermal and short wavelength geoid anomalies reveals the existence of small-scale convective systems in the upper mantle, with scales ranging from 500 km to 700 km. It is reasonable to suggest that these small-scale convective systems probably control the regional tectonic structure and the dynamical processes of the lithosphere. Here we have calculated the patterns of small-scale convection in the upper mantle for the Eurasian region (20°E~170°E,15°N~75°N), using the anomaly of isostatic gravity. The results show that the regional lithospheric tectonics is strongly correlated with the upper mantle flow in the Eurasian region. Two intensive convective belts against the weak background convection can be recognized from convection patterns in this region: Alpine-Himalayan collision belt and West Pacific island arc-underthrust belt. Alpine-Himalayan belt is caused by the collision between the northern plate (Eurasian plate) and the southern plates (African plate and Indian plate). West Pacific island arc-underthrust belt is caused by the subduction of the Pacific plate beneath the Eurasian plate. Both of them are also seismotectonic belts. The collision and the subduction are two important geological events occurred since Mesozoic era and Cenozoic era in the Eurasian region. Therefore, the mantle flows may be one of the main driving forces of two events. In addition, most plate boundaries in this region can be recognized and the characteristics of upper mantle convection are different completely between the Eurasian plate and the plates around it (African plate, Arabian plate, Indian plate, Philippine Sea plate and Pacific plate). Main structures and geodynamic characteristics of the Eurasian can also be explained by our model results. The Tibet plateau is located in the intensive convective belt. Around the belt, the upwelling materials push the lithosphere to lift unitarily and form the plateau. Towards the north of the Tibet

  5. No evidence of association between common European mitochondrial DNA variants in Alzheimer, Parkinson, and migraine in the Spanish population.

    PubMed

    Fachal, Laura; Mosquera-Miguel, Ana; Pastor, Pau; Ortega-Cubero, Sara; Lorenzo, Elena; Oterino-Durán, Agustín; Toriello, María; Quintáns, Beatriz; Camiña-Tato, Montse; Sesar, Angel; Vega, Ana; Sobrido, María-Jesús; Salas, Antonio

    2015-01-01

    Certain mitochondrial DNA (mtDNA) variants and haplogroups have been found to be associated with neurological disorders. Several studies have suggested that mtDNA variation could have an etiologic role in these disorders by affecting the ATP production on high-energy demanding organs, such as the brain. We have analyzed 15 mtDNA SNPs (mtSNPs) in five cohorts of cases presenting Alzheimer disease (AD), Parkinson disease (PD), and migraine, and in controls, to evaluate the role mtDNA variation in disease risk. Association tests were undertaken both for mtSNPs and mitochondrial haplogroups. No significant association was detected for any mtSNP or haplogroup in AD and PD cohorts. Two mtSNPs were associated with one migraine cohort after correcting for multiple tests, namely, T4216C and G13708A and haplogroup J (FDR q-value = 0.02; Santiago's cohort). However, this association was not confirmed in a second replication migraine series. A review of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD, PD, and migraine. A detailed inspection of the literature highlights the need for performing more rigorous methodological and statistical standards in mtDNA genetic association studies aimed to avoid false positive results of association between mtDNA variants and neurological diseases. PMID:25349034

  6. Mitochondrial DNA of protohistoric remains of an Arikara population from South Dakota: implications for the macro-Siouan language hypothesis.

    PubMed

    Lawrence, Diana M; Kemp, Brian M; Eshleman, Jason; Jantz, Richard L; Snow, Meradeth; George, Debra; Smith, David Glenn

    2010-04-01

    Mitochondrial DNA (mtDNA) was extracted from skeletal remains excavated from three Arikara sites in South Dakota occupied between AD 1600 and 1832. The diagnostic markers of four mtDNA haplogroups to which most Native Americans belong (A, B, C, and D) were successfully identified in the extracts of 55 (87%) of the 63 samples studied. The frequencies of the four haplogroups were 42%, 29%, 22%, and 7%, respectively, and principal coordinates analysis and Fisher's exact tests were conducted to compare these haplogroup frequencies with those from other populations. Both analyses showed closer similarity among the Mohawk, Arikara, and Sioux populations than between any of these three and any other of the comparison populations. Portions of the first hypervariable segment (HVSI) of the mitochondrial genome were successfully amplified and sequenced for 42 of these 55 samples, and haplotype networks were constructed for two of the four haplogroups. The sharing of highly derived lineages suggests that some recent admixture of the Arikara with Algonquian-speaking and Siouan-speaking groups has occurred. The Arikara shared more ancient lineages with both Siouan and Cherokee populations than with any other population, consistent with the Macro-Siouan language hypothesis that Iroquoian, Siouan, and Caddoan languages share a relatively recent common ancestry. PMID:20649398

  7. Improved phylogenetic resolution and rapid diversification of Y-chromosome haplogroup K-M526 in Southeast Asia

    PubMed Central

    Karafet, Tatiana M; Mendez, Fernando L; Sudoyo, Herawati; Lansing, J Stephen; Hammer, Michael F

    2015-01-01

    The highly structured distribution of Y-chromosome haplogroups suggests that current patterns of variation may be informative of past population processes. However, limited phylogenetic resolution, particularly of subclades within haplogroup K, has obscured the relationships of lineages that are common across Eurasia. Here we genotype 13 new highly informative single-nucleotide polymorphisms in a worldwide sample of 4413 males that carry the derived allele at M526, and reconstruct an NRY haplogroup tree with significantly higher resolution for the major clade within haplogroup K, K-M526. Although K-M526 was previously characterized by a single polytomy of eight major branches, the phylogenetic structure of haplogroup K-M526 is now resolved into four major subclades (K2a–d). The largest of these subclades, K2b, is divided into two clusters: K2b1 and K2b2. K2b1 combines the previously known haplogroups M, S, K-P60 and K-P79, whereas K2b2 comprises haplogroups P and its subhaplogroups Q and R. Interestingly, the monophyletic group formed by haplogroups R and Q, which make up the majority of paternal lineages in Europe, Central Asia and the Americas, represents the only subclade with K2b that is not geographically restricted to Southeast Asia and Oceania. Estimates of the interval times for the branching events between M9 and P295 point to an initial rapid diversification process of K-M526 that likely occurred in Southeast Asia, with subsequent westward expansions of the ancestors of haplogroups R and Q. PMID:24896152

  8. Larger genetic differences within africans than between Africans and Eurasians.

    PubMed Central

    Yu, Ning; Chen, Feng-Chi; Ota, Satoshi; Jorde, Lynn B; Pamilo, Pekka; Patthy, Laszlo; Ramsay, Michele; Jenkins, Trefor; Shyue, Song-Kun; Li, Wen-Hsiung

    2002-01-01

    The worldwide pattern of single nucleotide polymorphism (SNP) variation is of great interest to human geneticists, population geneticists, and evolutionists, but remains incompletely understood. We studied the pattern in noncoding regions, because they are less affected by natural selection than are coding regions. Thus, it can reflect better the history of human evolution and can serve as a baseline for understanding the maintenance of SNPs in human populations. We sequenced 50 noncoding DNA segments each approximately 500 bp long in 10 Africans, 10 Europeans, and 10 Asians. An analysis of the data suggests that the sampling scheme is adequate for our purpose. The average nucleotide diversity (pi) for the 50 segments is only 0.061% +/- 0.010% among Asians and 0.064% +/- 0.011% among Europeans but almost twice as high (0.115% +/- 0.016%) among Africans. The African diversity estimate is even higher than that between Africans and Eurasians (0.096% +/- 0.012%). From available data for noncoding autosomal regions (total length = 47,038 bp) and X-linked regions (47,421 bp), we estimated the pi-values for autosomal regions to be 0.105, 0.070, 0.069, and 0.097% for Africans, Asians, Europeans, and between Africans and Eurasians, and the corresponding values for X-linked regions to be 0.088, 0.042, 0.053, and 0.082%. Thus, Africans differ from one another slightly more than from Eurasians, and the genetic diversity in Eurasians is largely a subset of that in Africans, supporting the out of Africa model of human evolution. Clearly, one must specify the geographic origins of the individuals sampled when studying pi or SNP density. PMID:12019240

  9. Y chromosome haplogroup distribution in Indo-European speaking tribes of Gujarat, western India.

    PubMed

    Khurana, Priyanka; Aggarwal, Aastha; Mitra, Siuli; Italia, Yazdi M; Saraswathy, Kallur N; Chandrasekar, Adimoolam; Kshatriya, Gautam K

    2014-01-01

    The present study was carried out in the Indo-European speaking tribal population groups of Southern Gujarat, India to investigate and reconstruct their paternal population structure and population histories. The role of language, ethnicity and geography in determining the observed pattern of Y haplogroup clustering in the study populations was also examined. A set of 48 bi-allelic markers on the non-recombining region of Y chromosome (NRY) were analysed in 284 males; representing nine Indo-European speaking tribal populations. The genetic structure of the populations revealed that none of these groups was overtly admixed or completely isolated. However, elevated haplogroup diversity and FST value point towards greater diversity and differentiation which suggests the possibility of early demographic expansion of the study groups. The phylogenetic analysis revealed 13 paternal lineages, of which six haplogroups: C5, H1a*, H2, J2, R1a1* and R2 accounted for a major portion of the Y chromosome diversity. The higher frequency of the six haplogroups and the pattern of clustering in the populations indicated overlapping of haplogroups with West and Central Asian populations. Other analyses undertaken on the population affiliations revealed that the Indo-European speaking populations along with the Dravidian speaking groups of southern India have an influence on the tribal groups of Gujarat. The vital role of geography in determining the distribution of Y lineages was also noticed. This implies that although language plays a vital role in determining the distribution of Y lineages, the present day linguistic affiliation of any population in India for reconstructing the demographic history of the country should be considered with caution. PMID:24614885

  10. Y Chromosome Haplogroup Distribution in Indo-European Speaking Tribes of Gujarat, Western India

    PubMed Central

    Aggarwal, Aastha; Mitra, Siuli; Italia, Yazdi M.; Saraswathy, Kallur N.; Chandrasekar, Adimoolam

    2014-01-01

    The present study was carried out in the Indo-European speaking tribal population groups of Southern Gujarat, India to investigate and reconstruct their paternal population structure and population histories. The role of language, ethnicity and geography in determining the observed pattern of Y haplogroup clustering in the study populations was also examined. A set of 48 bi-allelic markers on the non-recombining region of Y chromosome (NRY) were analysed in 284 males; representing nine Indo-European speaking tribal populations. The genetic structure of the populations revealed that none of these groups was overtly admixed or completely isolated. However, elevated haplogroup diversity and FST value point towards greater diversity and differentiation which suggests the possibility of early demographic expansion of the study groups. The phylogenetic analysis revealed 13 paternal lineages, of which six haplogroups: C5, H1a*, H2, J2, R1a1* and R2 accounted for a major portion of the Y chromosome diversity. The higher frequency of the six haplogroups and the pattern of clustering in the populations indicated overlapping of haplogroups with West and Central Asian populations. Other analyses undertaken on the population affiliations revealed that the Indo-European speaking populations along with the Dravidian speaking groups of southern India have an influence on the tribal groups of Gujarat. The vital role of geography in determining the distribution of Y lineages was also noticed. This implies that although language plays a vital role in determining the distribution of Y lineages, the present day linguistic affiliation of any population in India for reconstructing the demographic history of the country should be considered with caution. PMID:24614885

  11. Mitochondrial DNA D-loop sequence variation in maternal lineages of Iranian native horses.

    PubMed

    Moridi, M; Masoudi, A A; Vaez Torshizi, R; Hill, E W

    2013-04-01

    To understand the origin and genetic diversity of Iranian native horses, mitochondrial DNA (mtDNA) D-loop sequences were generated for 95 horses from five breeds sampled in eight geographical locations in Iran. Sequence analysis of a 247-bp segment revealed a total of 27 haplotypes with 38 polymorphic sites. Twelve of 19 mtDNA haplogroups were identified in the samples. The most common haplotypes were found within haplogroup X2. Within-population haplotype and nucleotide diversities of the five breeds ranged from 0.838 ± 0.056 to 0.974 ± 0.022 and 0.011 ± 0.002 to 0.021 ± 0.001 respectively, indicating a relatively high genetic diversity in Iranian horses. The identification of several ancient sequences common between the breeds suggests that the lineage of the majority of Iranian horse breeds is old and obviously originated from a vast number of mares. We found in all native Iranian horse breeds lineages of the haplogroups D and K, which is concordant with the previous findings of Asian origins of these haplogroups. The presence of haplotypes E and K in our study also is consistent with a geographical west-east direction of increasing frequency of these haplotypes and a genetic fusion in Iranian horse breeds. PMID:22732008

  12. Identification of Whole Mitochondrial Genomes from Venezuela and Implications on Regional Phylogenies in South America.

    PubMed

    Lee, Esther J; Merriwether, D Andrew

    2015-01-01

    Recent studies have expanded and refined the founding haplogroups of the Americas using whole mitochondrial (mtDNA) genome analysis. In addition to pan-American lineages, specific variants have been identified in a number of studies that show higher frequencies in restricted geographical areas. To further characterize Native American maternal lineages and specifically examine local patterns within South America, we analyzed 12 maternally unrelated Yekuana whole mtDNA genomes from one village (Sharamaña) that include the four major Native American haplogroups A2, B2, C1, and D1. Based on our results, we propose a reconfiguration of one subhaplogroup A2 (A2aa) that is specific to South America and identify other singleton branches across the four haplogroups. Furthermore, we show nucleotide diversity values that increase from north to south for haplogroups C1 and D1. The results from our work add to the growing mitogenomic data that highlight local phylogenies and support the rapid genetic differentiation of South American populations, which has been correlated with the linguistic diversity in the region by previous studies. PMID:26416320

  13. Mitochondrial vasculopathy

    PubMed Central

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-01-01

    Mitochondrial disorders (MIDs) are usually multisystem disorders (mitochondrial multiorgan disorder syndrome) either on from onset or starting at a point during the disease course. Most frequently affected tissues are those with a high oxygen demand such as the central nervous system, the muscle, endocrine glands, or the myocardium. Recently, it has been shown that rarely also the arteries may be affected (mitochondrial arteriopathy). This review focuses on the type, diagnosis, and treatment of mitochondrial vasculopathy in MID patients. A literature search using appropriate search terms was carried out. Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy. Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy, migraine-like headache, stroke-like episodes, or peripheral retinopathy. Mitochondrial macroangiopathy manifests as atherosclerosis, ectasia of arteries, aneurysm formation, dissection, or spontaneous rupture of arteries. The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes. Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes. Mitochondrial vasculopathy exists and manifests as micro- or macroangiopathy. Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications. PMID:27231520

  14. Mitochondrial Cardiomyopathies

    PubMed Central

    El-Hattab, Ayman W.; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20–40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. PMID:27504452

  15. Mitochondrial vasculopathy.

    PubMed

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-05-26

    Mitochondrial disorders (MIDs) are usually multisystem disorders (mitochondrial multiorgan disorder syndrome) either on from onset or starting at a point during the disease course. Most frequently affected tissues are those with a high oxygen demand such as the central nervous system, the muscle, endocrine glands, or the myocardium. Recently, it has been shown that rarely also the arteries may be affected (mitochondrial arteriopathy). This review focuses on the type, diagnosis, and treatment of mitochondrial vasculopathy in MID patients. A literature search using appropriate search terms was carried out. Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy. Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy, migraine-like headache, stroke-like episodes, or peripheral retinopathy. Mitochondrial macroangiopathy manifests as atherosclerosis, ectasia of arteries, aneurysm formation, dissection, or spontaneous rupture of arteries. The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes. Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes. Mitochondrial vasculopathy exists and manifests as micro- or macroangiopathy. Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications. PMID:27231520

  16. Mitochondrial Cardiomyopathies.

    PubMed

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. PMID:27504452

  17. AmericaPlex26: A SNaPshot Multiplex System for Genotyping the Main Human Mitochondrial Founder Lineages of the Americas

    PubMed Central

    Coutinho, Alexandra; Valverde, Guido; Fehren-Schmitz, Lars; Cooper, Alan; Barreto Romero, Maria Inés; Espinoza, Isabel Flores; Llamas, Bastien; Haak, Wolfgang

    2014-01-01

    Phylogeographic studies have described a reduced genetic diversity in Native American populations, indicative of one or more bottleneck events during the peopling and prehistory of the Americas. Classical sequencing approaches targeting the mitochondrial diversity have reported the presence of five major haplogroups, namely A, B, C, D and X, whereas the advent of complete mitochondrial genome sequencing has recently refined the number of founder lineages within the given diversity to 15 sub-haplogroups. We developed and optimized a SNaPshot assay to study the mitochondrial diversity in pre-Columbian Native American populations by simultaneous typing of 26 single nucleotide polymorphisms (SNPs) characterising Native American sub-haplogroups. Our assay proved to be highly sensitive with respect to starting concentrations of target DNA and could be applied successfully to a range of ancient human skeletal material from South America from various time periods. The AmericaPlex26 is a powerful assay with enhanced phylogenetic resolution that allows time- and cost-efficient mitochondrial DNA sub-typing from valuable ancient specimens. It can be applied in addition or alternative to standard sequencing of the D-loop region in forensics, ancestry testing, and population studies, or where full-resolution mitochondrial genome sequencing is not feasible. PMID:24671218

  18. Phylogeny and patterns of diversity of goat mtDNA haplogroup A revealed by resequencing complete mitogenomes.

    PubMed

    Doro, Maria Grazia; Piras, Daniela; Leoni, Giovanni Giuseppe; Casu, Giuseppina; Vaccargiu, Simona; Parracciani, Debora; Naitana, Salvatore; Pirastu, Mario; Novelletto, Andrea

    2014-01-01

    We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg) A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia. PMID:24763315

  19. Population structure and identification of two matrilinear and one patrilinear mitochondrial lineages in the mussel Mytella charruana

    NASA Astrophysics Data System (ADS)

    de Souza, Thainara Oliveira; Alves, Francisco Arimateia dos Santos; Beasley, Colin Robert; de Simone, Luiz Ricardo Lopes; Marques-Silva, Nelane do Socorro; Santos-Neto, Guilherme da Cruz; Tagliaro, Claudia Helena

    2015-04-01

    The mitochondrial gene cytochrome c oxidase subunit I (COI) was sequenced from Mytella charruana (N = 243) at 10 Brazilian coastal localities to search for cryptic species, doubly uniparental inheritance and investigate genetic population structure and demography. Three haplogroups were found: two matrilinear (A and B) in males and females, and one patrilinear (C) found only in males. The p-distances were 0.0624 (A and B), 0.2097 (A and C) and 0.2081 (B and C). Coalescence of M. charruana occurred around 12.5 Mya, and the origins of the lineages were 3.4 and 4 Mya (matrilinear A and B) and 51.2 Mya (patrilinear), which split before the separation of the genera Perna and Mytella. All individuals from the northern coast of Brazil belonged to haplogroup A, whereas haplogroup B predominated among individuals from the eastern and northeastern coasts, with one exception, Goiana. Haplogroup C was found in males from the northern to the eastern coast. GenBank sequences of M. charruana from Colombia, Ecuador and four populations introduced to the USA joined Brazilian haplogroup B. Nuclear gene 18S-ITS1 sequences confirmed that all specimens belong to the same species. Four populations from the northern coast of Brazil were homogenous with evidence of recent population expansion. All populations from the northeastern and eastern coasts of Brazil were significantly structured (pairwise FST and AMOVA). The heterogeneity among Brazilian populations requires that relocation for aquaculture be preceded by genetic identification of the haplogroups. Differences in salinity and temperature may have selected for distinct lineages of mussels and changing conditions in coasts and estuaries may allow only resistant lineages of mussel to persist with the loss of others. In the light of global climate change, more detailed data on temperature, pH, salinity and local currents could help explain the genetic structuring observed among populations of Brazilian M. charruana.

  20. The phylogeography of Eurasian Fraxinus species reveals ancient transcontinental reticulation.

    PubMed

    Hinsinger, Damien D; Gaudeul, Myriam; Couloux, Arnaud; Bousquet, Jean; Frascaria-Lacoste, Nathalie

    2014-08-01

    To investigate the biogeographical history of ashes species of the Eurasian section Fraxinus and to test the hypothesis of ancient reticulations, we sequenced nuclear DNA (nETS and nITS, 1075 bp) for 533 samples and scored AFLP for 63 samples of Eurasian ashes within the section Fraxinus. The nITS phylogeny retrieved the classical view of the evolution of the section, whereas nETS phylogeny indicated an unexpected separation of F. angustifolia in two paraphyletic groups, respectively found in southeastern Europe and in the other parts of the Mediterranean basin. In the nETS phylogeny, the former group was closely related to F. excelsior, whereas the later was closely related to F. mandshurica, a species which is restricted nowadays to northeastern Asia. This topological incongruence between the two loci indicated the occurrence of an ancient reticulation between European and Asian ash species. Several other ancient reticulation events between the two European species and the other species of the section were supported by the posterior predictive checking method. Some of these reticulation events would have occurred during the Miocene, when climatic variations may have lead these species to expand their distribution range and come into contact. The recurrent reticulations observed among Eurasian ash species indicate that they should be considered as conspecific taxa, with subspecific status for some groups. Altogether, the results of the present study provide a rare documented evidence for the occurrence of multiple ancient reticulations within a group of temperate tree taxa with modern disjunct distributions in Eurasia. These ancient reticulation events indicate that the speciation process is slow in ashes, necessitating long periods of geographical isolation. The implications for speciation processes in temperate trees with similar life history and reproductive biology are discussed. PMID:24795215

  1. Evidence of Mitochondrial Dysfunction within the Complex Genetic Etiology of Schizophrenia

    PubMed Central

    Hjelm, Brooke E.; Rollins, Brandi; Mamdani, Firoza; Lauterborn, Julie C.; Kirov, George; Lynch, Gary; Gall, Christine M.; Sequeira, Adolfo; Vawter, Marquis P.

    2015-01-01

    Genetic evidence has supported the hypothesis that schizophrenia (SZ) is a polygenic disorder caused by the disruption in function of several or many genes. The most common and reproducible cellular phenotype associated with SZ is a reduction in dendritic spines within the neocortex, suggesting alterations in dendritic architecture may cause aberrant cortical circuitry and SZ symptoms. Here, we review evidence supporting a multifactorial model of mitochondrial dysfunction in SZ etiology and discuss how these multiple paths to mitochondrial dysfunction may contribute to dendritic spine loss and/or underdevelopment in some SZ subjects. The pathophysiological role of mitochondrial dysfunction in SZ is based upon genomic analyses of both the mitochondrial genome and nuclear genes involved in mitochondrial function. Previous studies and preliminary data suggest SZ is associated with specific alleles and haplogroups of the mitochondrial genome, and also correlates with a reduction in mitochondrial copy number and an increase in synonymous and nonsynonymous substitutions of mitochondrial DNA. Mitochondrial dysfunction has also been widely implicated in SZ by genome-wide association, exome sequencing, altered gene expression, proteomics, microscopy analyses, and induced pluripotent stem cell studies. Together, these data support the hypothesis that SZ is a polygenic disorder with an enrichment of mitochondrial targets. PMID:26550561

  2. Analysis of 22 Y chromosomal STR haplotypes and Y haplogroup distribution in Pathans of Pakistan.

    PubMed

    Lee, Eun Young; Shin, Kyoung-Jin; Rakha, Allah; Sim, Jeong Eun; Park, Myung Jin; Kim, Na Young; Yang, Woo Ick; Lee, Hwan Young

    2014-07-01

    We analyzed haplotypes for 22 Y chromosomal STRs (Y-STRs), including 17 Yfiler loci (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DY438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4) and five additional STRs (DYS388, DYS446, DYS447, DYS449 and DYS464), and Y chromosomal haplogroup distribution in 270 unrelated individuals from the Pathans residing in the Federally Administered Tribal Areas and the North-West Frontier Province of Pakistan using in-house multiplex PCR systems. Each Y-STR showed diversities ranging from 0.2506 to 0.8538, and the discriminatory capacity (DC) was 73.7% with 199 observed haplotypes using 17 Yfiler loci. By the addition of 5 Y-STRs to the Yfiler system, the DC was increased to 85.2% while showing 230 observed haplotypes. Among the additional 5 Y-STRs, DYS446, DYS447 and DYS449 were major contributors to enhancing discrimination. In the analysis of molecular variance, the Pathans of this study showed significant differences from other Pathan populations as well as neighboring population sets. In Y-SNP analysis, a total of 12 Y chromosomal haplogroups were observed and the most frequent haplogroup was R1a1a with 49.3% frequency. To obtain insights on the origin of Pathans, the network analysis was performed for the haplogroups G and Q observed from the Pathans and the Jewish population groups including Ashkenazim and Sephardim, but little support for a Jewish origin could be found. In the present study, we report Y-STR population data in Pathans of Pakistan, and we emphasize the need for adding additional markers to the commonly used 17 Yfiler loci to achieve more improved discriminatory capacity in a population with low genetic diversity. PMID:24709582

  3. Refined phylogenetic structure of an abundant East Asian Y-chromosomal haplogroup O*-M134.

    PubMed

    Ning, Chao; Yan, Shi; Hu, Kang; Cui, Yin-Qiu; Jin, Li

    2016-02-01

    The human Y-chromosome haplogroup O-M134 is one of the most abundant paternal lineages in East Asian populations, comprising ~13% of Han Chinese males, and also common in Kazakh, Korean, Japanese, Thai and so on. Despite its considerable prevalence, its current substructure is poorly resolved with only one downstream marker (M117) previously investigated. Here we address this deficiency by investigating some single-nucleotide polymorphisms (SNPs) previously reported being potentially associated with O-M134 based on high-throughput DNA-sequencing data. Using a panel of 1301 Chinese males we first identified 154 haplogroup O-M134 subjects. We then investigated the phylogenetic structure within this haplogroup using 10 SNPs (F444, F629, F3451, F46, F48, F209, F2887, F3386, F1739 and F152). Two major branches were identified, O-M117 and O-F444 and the latter was further divided into two main subclades, O-F629 and O-F3451, accounting for 10.84 and 0.92% of the Han Chinese, respectively. This update of O-M134 diversification permits better resolution of male lineages in population studies of East Asia. PMID:26306641

  4. Evaluation of Y chromosomal SNP haplogrouping in the HID-Ion AmpliSeq™ Identity Panel.

    PubMed

    Ochiai, Eriko; Minaguchi, Kiyoshi; Nambiar, Phrabhakaran; Kakimoto, Yu; Satoh, Fumiko; Nakatome, Masato; Miyashita, Keiko; Osawa, Motoki

    2016-09-01

    The Y chromosomal haplogroup determined from single nucleotide polymorphism (SNP) combinations is a valuable genetic marker to study ancestral male lineage and ethical distribution. Next-generation sequencing has been developed for widely diverse genetics fields. For this study, we demonstrate 34 Y-SNP typing employing the Ion PGM™ system to perform haplogrouping. DNA libraries were constructed using the HID-Ion AmpliSeq™ Identity Panel. Emulsion PCR was performed, then DNA sequences were analyzed on the Ion 314 and 316 Chip Kit v2. Some difficulties became apparent during the analytic processes. No-call was reported at rs2032599 and M479 in six samples, in which the least coverage was observed at M479. A minor misreading occurred at rs2032631 and M479. A real time PCR experiment using other pairs of oligonucleotide primers showed that these events might result from the flanking sequence. Finally, Y haplogroup was determined completely for 81 unrelated males including Japanese (n=59) and Malay (n=22) subjects. The allelic divergence differed between the two populations. In comparison with the conventional Sanger method, next-generation sequencing provides a comprehensive SNP analysis with convenient procedures, but further system improvement is necessary. PMID:27591541

  5. Whole mitochondrial DNA sequencing in Alpine populations and the genetic history of the Neolithic Tyrolean Iceman.

    PubMed

    Coia, V; Cipollini, G; Anagnostou, P; Maixner, F; Battaggia, C; Brisighelli, F; Gómez-Carballa, A; Destro Bisol, G; Salas, A; Zink, A

    2016-01-01

    The Tyrolean Iceman is an extraordinarily well-preserved natural mummy that lived south of the Alpine ridge ~5,200 years before present (ybp), during the Copper Age. Despite studies that have investigated his genetic profile, the relation of the Iceman´s maternal lineage with present-day mitochondrial variation remains elusive. Studies of the Iceman have shown that his mitochondrial DNA (mtDNA) belongs to a novel lineage of haplogroup K1 (K1f) not found in extant populations. We analyzed the complete mtDNA sequences of 42 haplogroup K bearing individuals from populations of the Eastern Italian Alps - putatively in genetic continuity with the Tyrolean Iceman-and compared his mitogenome with a large dataset of worldwide K1 sequences. Our results allow a re-definition of the K1 phylogeny, and indicate that the K1f haplogroup is absent or rare in present-day populations. We suggest that mtDNA Iceman´s lineage could have disappeared during demographic events starting in Europe from ~5,000 ybp. Based on the comparison of our results with published data, we propose a scenario that could explain the apparent contrast between the phylogeographic features of maternal and paternal lineages of the Tyrolean Iceman within the context of the demographic dynamics happening in Europe from 8,000 ybp. PMID:26764605

  6. Prevalence of mitochondrial diabetes in southwestern Finland: a molecular epidemiological study.

    PubMed

    Martikainen, Mika H; Rönnemaa, Tapani; Majamaa, Kari

    2013-10-01

    Mitochondrial diabetes and deafness (MIDD) is a subtype of diabetes mellitus (DM) that most commonly results from the m.3243A > G mutation in mitochondrial DNA (mtDNA). Sensorineural hearing loss is a typical accompanying feature. Previous studies have suggested a prevalence of ~1-1.5 % for MIDD. We studied the molecular epidemiology of MIDD among young (aged 18-45 years) adults in a defined population in southwestern Finland. Of the identified cohort of 1,532 patients with DM, we received blood samples of 299 patients and analyzed them for the m.3243A > G mutation and for mtDNA haplogroups. We found three DM patients (1.0 %) with the m.3243A > G mutation. All the three patients with DM and m.3243A > G also had severe hearing impairment that required use of hearing aid. MtDNA haplogroup U was more prevalent among patients with maternal family history of DM. We conclude that among young adults, ~1 % of all DM is associated with the m.3243A > G mutation. We suggest that all patients with both DM and hearing impairment, at least in this age group, should undergo investigation for this mutation. Furthermore, our results suggest that mtDNA haplogroup U is associated with maternal family history of DM. PMID:22492248

  7. No association between typical European mitochondrial variation and prostate cancer risk in a Spanish cohort.

    PubMed

    Fachal, Laura; Gómez-Caamaño, Antonio; Alvarez Iglesias, Vanesa; Gómez Carballa, Alberto; Calvo, Patricia; Salas, Antonio; Vega, Ana

    2014-07-01

    Mitochondrial common variants (mtSNPs) and the haplogroups defined by them have been inconsistently correlated with increased prostate cancer risk. Here we aimed to investigate the influence of the mitochondrial genetic background on prostate cancer. A total of 15 single-nucleotide polymorphisms (SNPs) representing the common European branches of the mtDNA phylogeny were analyzed in a cohort of 620 Spanish prostate cancer patients and 616 matched population-based controls. Association tests were computed on mtSNPs and haplogroups. None of the evaluated mtSNPs or haplogroups were statistically associated with prostate cancer risk in our Spanish cohort. We show that previous association findings do not rest on solid grounds given that all of them (i) were based on underpowered studies, (ii) did not control for population stratification, (iii) lacked replication/confirmation cohorts, and (iv) and did not control for multiple test corrections. Taken together, a critical reassessment of the previous literature and the results obtained in the present study suggest that mtDNA common European variants are not correlated with increases in the risk for prostate cancer. PMID:24898828

  8. Whole mitochondrial DNA sequencing in Alpine populations and the genetic history of the Neolithic Tyrolean Iceman

    PubMed Central

    Coia, V.; Cipollini, G.; Anagnostou, P.; Maixner, F.; Battaggia, C.; Brisighelli, F.; Gómez-Carballa, A; Destro Bisol, G.; Salas, A.; Zink, A.

    2016-01-01

    The Tyrolean Iceman is an extraordinarily well-preserved natural mummy that lived south of the Alpine ridge ~5,200 years before present (ybp), during the Copper Age. Despite studies that have investigated his genetic profile, the relation of the Iceman´s maternal lineage with present-day mitochondrial variation remains elusive. Studies of the Iceman have shown that his mitochondrial DNA (mtDNA) belongs to a novel lineage of haplogroup K1 (K1f) not found in extant populations. We analyzed the complete mtDNA sequences of 42 haplogroup K bearing individuals from populations of the Eastern Italian Alps – putatively in genetic continuity with the Tyrolean Iceman—and compared his mitogenome with a large dataset of worldwide K1 sequences. Our results allow a re-definition of the K1 phylogeny, and indicate that the K1f haplogroup is absent or rare in present-day populations. We suggest that mtDNA Iceman´s lineage could have disappeared during demographic events starting in Europe from ~5,000 ybp. Based on the comparison of our results with published data, we propose a scenario that could explain the apparent contrast between the phylogeographic features of maternal and paternal lineages of the Tyrolean Iceman within the context of the demographic dynamics happening in Europe from 8,000 ybp. PMID:26764605

  9. Mitochondrial DNA diversity in Mennonite communities from the midwestern United States.

    PubMed

    Melton, Phillip E; Mosher, M J; Rubicz, R; Zlojutro, M; Crawford, M H

    2010-06-01

    We examined mitochondrial DNA (mtDNA) variation in six Mennonite communities from Kansas (Goessel, Lone Tree, Garden View, Meridian, and Garden City) and Nebraska (Henderson) to determine their genetic structure and its relationship to population history. Mitochondrial DNA haplogroup and haplotype information were obtained from blood samples from 118 individuals. Molecular genetic variation was analyzed using diversity measures, neutrality test statistics, spatial analysis of molecular variance (SAMOVA), and multidimensional scaling plots. The Mennonite samples exhibited eight western European mtDNA haplogroups: H, HV0, I, J, K, T, U, and X. Comparable to other populations of European descent, haplogroup H was the most frequent in all six communities and ranged from 35% in Lone Tree to 75% in Old Order Mennonites from Garden City. Fifty-eight different mtDNA haplotypes were found in these groups with only one shared among all six populations. Haplotype diversities varied from 0.81 in Goessel to 0.96 in Henderson and Garden View. Multivariate statistical analysis of these populations indicates that these Anabaptist communities formed new congregations by fissioning along familial lines. Population subdivision of these communities into congregations supports previously documented patterns of fission-fusion. These haploid molecular data provide a more accurate reflection of biological relationships between midwestern Mennonite communities than evidence based on classical genetic markers. PMID:20649384

  10. Mitochondrial Diseases

    PubMed Central

    Lee, Young-Mock

    2012-01-01

    Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the main part of cellular energy in the form of ATP. Although several proteins related with signalling, assembling, transporting, and enzymatic function can be impaired in mitochondrial diseases, most frequently the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial diseases usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Neuromuscular system is frequently affected in mitochondrial diseases. Although there is actually no specific therapy and cure for mitochondrial diseases, the understanding of the pathophysiology may further facilitate the diagnostic approach and open perspectives to future in mitochondrial diseases. PMID:24649452