Mitochondrial DNA haplogroup associated with sperm motility in the Han population

In this study, we aimed to determine whether the main mitochondrial DNA （mtDNA） haplogroups of the Han people have an impact on spermatozoa motility, We recruited 312 men who were consecutively admitted to two affiliated hospitals of College of Medicine, Zhejiang University from May 2011 to April 2012 as part of fertility investigations. Semen and whole blood samples were collected from the men. We determined the mtDNA haplogroups by analysing the sequences of mtDNA hypervariable segment I and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes, No significant differences were found in the clinical characteristics of the mtDNA haplogroup R and non-R （P〉0.05）. Our results suggest that mtDNA haplogroup R is a strong independent predictor of sperm motility in the Han population, conferring a 2.97-fold （95% confidence interval： 1.74-4.48, P〈0.001） decreased chance of asthenozoospermia compared with those without haplogroup R.     

Common genes for non-syndromic deafness are uncommon in sub-Saharan Africa: A report from Nigeria

IntroductionLittle is known about the molecular epidemiology of deafness in sub-Saharan Africa (SSA). Even in Nigeria, the most populous African nation, no genetic studies of deafness have been conducted. This pioneering work aims at investigating the frequencies of gene mutations relatively common in other parts of the world (i.e. those in GJB2, GJB6, and mitochondrial DNA) among subjects from Nigeria with hearing loss (HL) with no evidence of acquired pathology or syndromic findings. In addition, we review the literature on the genetics of deafness in SSA.MethodWe evaluated 81 unrelated deaf probands from the Yoruba tribe residing in Ibadan, a suburban city in Nigeria, for the aetiology of their deafness. Subjects underwent genetic testing if their history was negative for an environmental cause and physical examination did not find evidence of a syndrome. Both exons of GJB2 and mitochondrial DNA flanking the 1555A>G mutations were PCR-amplified followed by Sanger sequencing. GJB6 deletions were screened via quantitative PCR.ResultWe identified 44 probands who had nonsyndromic deafness with no environmental cause. The age at study time ranged between 8 months and 45 years (mean = 24 years) and age at onset was congenital or prelingual (<age 2 years) in 37 (84%) probands and postlingual in 7 (16%) probands. Among these, 35 probands were the only affected members of their families (simplex cases), while there were at least two affected family members in nine cases (multiplex). Molecular analyses did not show a pathogenic variant in any one of the 44 probands studied.ConclusionGJB2, GJB6 and mitochondrial DNA 1555A>G mutations were not found among this initial cohort of the deaf in Nigeria. This makes imperative the search for other genes in the aetiology of HL in this population.     

Differentiation Effect of Pyruvate and Uridine on Cultured U937-ρ° Cells

ABSTRACT

The human pro-monocytic leukemia U937 cell line was previously reported to become ρ°cells after a long-term ethidium bromide exposure. In the authors' extensive PCR studies with different pairs of primers for the mtDNA molecule they showed that these U937-ρ° cells, after being cultured in their laboratory for a time, did replete their mtDNA. That the cells grew well in the normal medium (RPMI 1640 plus 10% fetal calf serum and 2 mM L-glutamine) as the parental cells also suggests that these cells contain functional mitochondria and mtDNA molecules. Further experiments showed that the cells cultured in the medium with pyruvate and uridine rather rapidly and strongly adhered on the culture flask walls while the cells cultured in the medium without pyruvate and uridine either floated or only very loosely covered the culture flask walls. Ultrastructural examination showed that the floating cells, which were often found in the culture without pyruvate and uridine, were rather similar to monocytes in nature, like the original U937 cells, while the attached larger cells appearing earlier in the culture with pyruvate and uridine demonstrated macrophage differentiation, indicating a differentiation effect of pyruvate and uridine on the cells.     

Ultrastructural Changes of Mitochondria in the Cultivated Skin Fibroblasts of Patients with Point Mutations in Mitochondrial DNA

Mitochondrial disorders represent a heterogeneous group of multisystem diseases with extreme variability in clinical phenotype. The diagnosis of mitochondrial disorders relies heavily on extensive biochemical and molecular analyses combined with morphological studies including electron microscopy. Although muscle is the tissue of choice for electron microscopic studies, the authors investigated cultivated human skin fibroblasts (HSF) harboring 3 different pathologic mtDNA mutations: 3243A > G, 8344A > G, 8993T > G. They addressed to the possibility of whether mtDNA mutations influence mitochondrial morphology in HSF and if ultrastructural changes of mitochondria may be used for differential diagnostics of mitochondrial disorders caused by mtDNA mutations. Ultrastructural analysis of patients' HSF revealed a heterogeneous mixture of mainly abnormal, partially swelling mitochondria with unusual and sparse cristae. The most characteristic cristal abnormalities were heterogeneity in size and shapes or their absence. Typical filamentous and branched mitochondria with numerous cristae as appeared in control HSF were almost not observed. In all lines of cultured HSF with various mtDNA mutations, similar ultrastructural abnormalities and severely changed mitochondrial interior were found, although no alterations in function and amount of OXPHOS were detected by routinely used biochemical methods in two lines of cultured HSF. This highlights the importance of morphological analysis, even in cultured fibroblasts, in diagnostics of mitochondrial disorders.     

Human mitochondrial DNA variation in Southern Italy

Background: Since prehistoric times Southern Italy has been a cultural crossroads of the Mediterranean basin. Genetic data on the peoples of Basilicata and Calabria are scarce and, particularly, no records on mtDNA variability have been published.

Aim: In this study mtDNA haplotypes of populations from Basilicata, Calabria and Sicily are compared with those of other Italian and Mediterranean populations, so as to investigate their genetic relationships.

Subjects and methods: A total of 341 individuals was analysed for mtDNA in order to provide their classification into haplogroups. Multivariate analysis was used to compare the studied populations with other Mediterranean samples; median-joining network analysis was applied to observe the relationship between the major lineages of the Southern Italians.

Results: The haplogroup distribution in the Southern Italian samples falls within the typical pattern of mtDNA variability of Western Eurasia. The comparison with other Mediterranean countries showed a substantial homogeneity of the area, which is probably related to the historic contact through the Mediterranean Sea.

Conclusion: The mtDNA analysis demonstrated that Southern Italy displays a typical pattern of Mediterranean basin variability, even though it appears plausible that Southern Italy was less affected by the effects of the Late Glacial Maximum, which reduced genetic diversity in Europe.     

Genetic ancestries in northwest Cambodia

A survey of the genetic ancestry of 125 Cambodian children resident in Siem Reap province was undertaken, based on eight Y-chromosome binary polymorphisms and sequencing of the mtDNA HV1 region. The data indicated a largely East Asian paternal ancestry and a local Southeast Asian maternal ancestry. The presence of Y-chromosomes P* and R1a1* was suggestive of a small but significant Indo-European male ancestral component, which probably reflects the history of Indian, and later European, influences on Cambodia.     

线粒体DNA4个多态性与宁夏汉族乳腺癌无相关性

 目的 探讨线粒体DNA（mtDNA）np16 189、np16 223、np16 519和D310区多态性及其交互作用与宁夏汉族乳腺癌及其临床病理特征的相关性。方法 用病例-对照法和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测195例乳腺癌患者和196例健康体检者各位点基因型,计算基因型频率,用χ2和OR（Odds ratio）检验分析单个、多个位点联合与乳腺癌的相关性,并分析各位点的基因型频率与乳腺癌临床病理特征的相关性。结果 1）mtDNA np16 189、np16 223和np16 519 3个位点的基因型频率在病例组和对照组中的分布无差异;D310区三种基因型在病例组高于对照组（OR=6. 6629,P＞0.05）,携带异质型的个体发生乳腺癌的危险性比携带突变型个体低（OR=0.216,95%CI为0.058～0.809）。2）4个多态性位点之间的交互作用在两组间无差异。3）4个多态性位点与乳腺癌临床病理特征间无相关性。结论 mtDNA np16 189、np16 223、np16 519和D310区及其交互作用与宁夏汉族乳腺癌无相关性。     

The influence of clan structure on the genetic variation in a single Ghanaian village

Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure. To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations. In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north-eastern Ghana. We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village. We also observed a deep male substructure within one of the clans in this village. Among all males, we observed only three Y-single-nucleotide polymorphism (SNP) haplogroups: E1b1a*-M2, E1b1a7a*-U174 and E1b1a8a*-U209, P277, P278. In contrast to the marked Y-chromosomal substructure, mitochondrial DNA HVS-1 sequence variation and autosomal short-tandem repeats variation patterns indicate high genetic diversities and a virtually random female-mediated gene flow among clans. On the extreme micro-geographical scale of this single Bimoba village, correspondence between the Y-chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure. If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale. Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large.