Transmission, genetic counselling, and prenatal diagnosis of mitochondrial DNA disease

No abstract available

No evidence for paternal mtDNA transmission to offspring or extra-embryonic tissues after ICSI.

Item does not contain fulltextThere is a risk that ICSI may increase the transmission of mtDNA diseases to children born after this technique. Knowledge of the fate and transmission of paternal mitochondrial DNA is important since mutations in mitochondrial DNA have been described in oligozoospermic males. We have used an adaptation of solid phase mini-sequencing to exclude the presence of levels of paternal mtDNA >0.001% in ICSI families. This method is more sensitive than those used in previous studies and is sufficient to detect the likely paternal contribution (approximately 0.1-0.5% from simple calculations of expected dilution during fertilization). Using this method, we were able to detect concentrations as low as 0.001% paternal mtDNA in a maternal mtDNA background. No paternal mtDNA was detected in the embryonic (blood or buccal swabs) tissue of children born after ICSI nor in extra-embryonic tissue (placenta or umbilical cord). In conclusion, we did not detect paternal mtDNA in blood, buccal swabs, placenta or umbilical cord of children born after ICSI. We have found no evidence that ICSI increases the risk of paternal transmission of mtDNA and hence of mtDNA disorders

74th ENMC International Workshop: Mitochondrial Diseases

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Look after they leap : illustrating the value of retrospective reports in employee turnover

The prevailing methodology for studying employee turnover is limited because it emphasizes prediction rather than understanding. This paper critiques this methodology and draws out the implications of an alternative: retrospective self-reporting, by actual leavers. Retrospective self-reporting has three main advantages. First, it allows direct assessment of actual incidents of turnover, so interventions can be informed by accounts of real events, instead of being based on inference. Second, it offers insight into the dynamic character of decisions to quit, which are often unpredictable or precipitated by sudden events. Third, it allows for assessment of the role of non-work factors. This makes a methodological contribution, allowing greater insight into the decision to quit, which is ontologically, socially and dynamically complex. It has implications for how we construe and manage turnover. The argument is illustrated by a recent study of 352 UK National Health Service nurse leavers but has wider implications for turnover in the public sector

Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility

Human mitochondrial DNA polymerase, encoded by POLG, contains a polyglutamine tract encoded by a CAG microsatellite repeat 1,2. Analysis of POLG genotypes in different populations identified an association between absence of the common, tenrepeat allele and male infertility typified by a range of sperm quality defects but excluding azoospermia

A prevalent POLG CAG microsatellite length allele in humans and African great apes

The human nuclear gene for the catalytic subunit of mitochondrial DNA polymerase γ (POLG) contains within its coding region a CAG microsatellite encoding a polyglutamine repeat. Previous studies demonstrated an association between length variation at this repeat and male infertility, suggesting a mechanism whereby the prevalent (CAG) 10 allele, which occurs at a frequency of >80% in different populations, could be maintained by selection. Sequence analysis of the POLG CAG microsatellite region of more than 1000 human chromosomes reveals that virtually all allelic variation at the locus is accounted for by length variation of the CAG repeat. Analysis of POLG from African great apes shows that a prevalent length allele is present in each species, although its exact length is species-specific. In common chimpanzee (Pan troglodytes) a number of different sequence variants contribute to the prevalent length allele, strongly supporting the idea that the length of the POLG microsatellite region, rather than its exact nucleotide or amino acid sequence, is what is maintained. Analysis of POLG in other primates indicates that the repeat has expanded from a shorter, glutamine-rich sequence, present in the common ancestor of Old and New World monkeys