Use of Mitochondrial Donation
Botros Rizk, Yakoub Khalaf in Controversies in Assisted Reproduction, 2020
Mutations in both nuclear DNA (nDNA) and mtDNA can result in defective mitochondria, incapable of normal oxidative phosphorylation; these can cause a range of heterogeneous, devastating diseases that mainly, but not exclusively, affect tissues with high energy requirements through aerobic metabolism, such as neural and muscle tissues (3). The prevalence of mitochondrial diseases caused by mutations in nDNA is estimated at 2.9 cases per 100,000 individuals, while that of mitochondrial diseases caused by mutations in mtDNA is 9.6 cases per 100,000 (4). These figures indicate an overall prevalence for mitochondrial disease of around 12–13 cases per 100,000. Elevated mutation rates of mtDNA are thought to arise from oxidative damage to DNA caused by reactive oxidative species produced in mitochondria. Mitochondrial diseases can occur at any age and manifest with a wide range of symptoms. The clinical features, including severity, of mtDNA-dependent mitochondrial diseases (see Table 12.1 for examples of these) are highly variable and depend on a number of factors, including the nature of the mtDNA mutation, the proportion of the mtDNA that is pathogenic versus normal—often called the degree of heteroplasmy—and the particular tissue distribution of the abnormal mtDNA. Polymorphisms in mtDNA also allow it to be classified into distinct haplotypes and, at a population level, into haplogroups. There have been reports that distinct haplogroups might impact on the occurrence and severity of mtDNA-dependent mitochondrial disease (5,6).
Mitochondrial DNA Mutations and Aging
Sara C. Zapico in Mechanisms Linking Aging, Diseases and Biological Age Estimation, 2017
As described above, human mtDNA is highly polymorphic. On the basis of certain SNPs present in mtDNA, which are well established and widely distributed, the human population can be divided into haplogroups (Malhi et al. 2003). Analysis of these polymorphisms from a wide range of human populations have revealed sets of ancestral mutations that define these haplogroups that have common ancestry and, because of uniparental inheritance, evolve independently from each other. Each of these haplogroups is defined by specific sets of associated mutations, thus allowing for a quick and precise classification of the mtDNA molecules within a certain population (De Benedictis et al. 1999). These associated mutations were suggested to affect coupling efficiency of the ETC enabling adaptation to life in different climatic conditions (Wallace 2005).
Ascaris
Dongyou Liu in Handbook of Foodborne Diseases, 2018
A comprehensive review on the genetic variation at regional and global scales and implications on epidemiological and transmission patterns was provided.30 These authors state that no molecular markers have been so far able to give a clear-cut definition of species boundaries in Ascaris, as no fixed differences have been observed. Although a strong genetic structuring related to host affiliation has been observed at local scale, such a scenario seems to be groundless at global scale, with degree of genetic differentiation seemingly mostly reliant on geography.31 Local-scale analyses of Ascaris roundworms have often shown contrasting results, for instance, a tree where the two clusters A and B depicted a strong influence of host affiliation, in analyzing samples from Guatemala.25 In contrast, networks where the character host affiliation is clearly paraphyletic were described in China32 and in Brazil.33 Although revealing some clustering differences according to host preference, shared haplotypes between African and Asian locations and between worms of human and pig origin were identified. The phylogenetic tree and the parsimony network then provided,20 based on samples from the two hosts and from different geographic areas, described a more complex situation with a cross-linked relationships among haplotypes, with no clear geographical or host-affiliation criteria to be obviously relevant in shaping haplogroups. In this study, molecular variance analysis underlined that accumulation of genetic variability is predominant at the individual and population level rather than at the level of groups, defined on geography or host affiliation.
Gene flow and phylogenetic analyses of paternal lineages in the Yi-Luo valley using Y-STR genetic markers
Published in Annals of Human Biology, 2021
Guang-Yao Fan, Dan-Lu Song, Hai-Ying Jin, Xing-Kai Zheng
Based on Y-STR loci information, each haplotype was assigned with a Y-linked haplogroup with the highest probability value by the Nevgen Y-DNA Haplogroup Predictor. To guarantee enough accuracy of the assignments, we only retained 1,102 Y-haplogroups assignments with probability assignment values over 70% (Supplementary Table S5). Their nomenclature complied with the guidelines of the International Society of Genetic Genealogy (ISSOG: https://isogg.org/tree). Finally, we constructed a phylogenetic network based on median-joining. The list of predicted haplogroups is shown in Supplementary Table S5. Six major haplogroups (C2, N1a2, O1a1, O1b1, O2a1, and O2a2) existed among the Yi-Luo valley population (Supplementary Table S6). The first three common haplogroups of the population were O2a2, C2, and O2a1, which represented 47.1% (519/1,102), 14.6% (161/1,102), and 12.5% (138/1,102), respectively. The complete haplogroups for each population of the Yi-Luo valley are shown in Supplementary Table S6. The Y-chromosome haplogroups and their frequency distribution in the populations of the Yi-Luo valley are noted in Supplementary Figure S3.
Differential mitochondrial genome in patients with Rheumatoid Arthritis
Published in Autoimmunity, 2021
Kumar Sagar Jaiswal, Shweta Khanna, Arup Ghosh, Prasanta Padhan, Sunil Kumar Raghav, Bhawna Gupta
Using the mtDNA sequence, we can determine the haplogroups using the mutation signature and comparing them with the HapMap data. In order to find the contribution of mtDNA haplogroup-specific mutations with the occurrence of RA, we performed a haplogroup analysis of RA samples and corresponding controls. A total of 23 RA and 17 HC samples were sequenced and all samples were combined into a resulting rooted tree which includes all related polymorphisms relative to the rCRS. In the sequenced 40 samples, 35 distinct haplogroups were observed. All samples were found to belong to four haplogroups M, N, R and U (Supplementary Figure S2). After the assignment of samples to haplogroups, the prevalence of each haplogroup was determined in each group. The population sequenced have a high frequency of haplogroup M lineage in both RA and HC groups.
Paternal lineages in southern Iberia provide time frames for gene flow from mainland Europe and the Mediterranean world
Published in Annals of Human Biology, 2019
Candela L. Hernández, Jean-Michel Dugoujon, Luis J. Sánchez-Martínez, Pedro Cuesta, Andrea Novelletto, Rosario Calderón
Haplogroup T is considered a rare but informative paternal lineage. It is detected mainly in the Near/Middle East and East Africa (Underhill etal. 2001; Luis etal. 2004; King etal. 2007; El-Sibai etal. 2009). The presence of haplogroup T in Europe, in general, is low (Mendez etal. 2011). The specific source of the European T chromosomes is still unclear. The evolutionary origin of haplogroup T seems to be in the Near East, with a history of complex dispersal where M70 was introduced into Europe and sub-Saharan Africa (Nogueiro etal. 2010; Mendez etal. 2011). However, because of the present level of resolution and the small number of Europeans with haplogroup T, reliable estimates of the timing of male gene flow towards Europe do not clearly indicate the dispersal route of this haplogroup (Nogueiro etal. 2010; Grugni etal. 2018).
