Pedigree derived mutation rate across the entire mitochondrial genome of the Norfolk Island population.

Estimates of mutation rates for various regions of the human mitochondrial genome (mtGenome) vary widely, depending on whether they are inferred using a phylogenetic approach or obtained directly from pedigrees. Traditionally, only the control region, or small portions of the coding region have been targeted for analysis due to the cost and effort required to produce whole mtGenome Sanger profiles. Here, we report one of the first pedigree derived mutation rates for the entire human mtGenome. The entire mtGenome from 225 individuals originating from Norfolk Island was analysed to estimate the pedigree derived mutation rate and compared against published mutation rates. These individuals were from 45 maternal lineages spanning 345 generational events. Mutation rates for various portions of the mtGenome were calculated. Nine mutations (including two transitions and seven cases of heteroplasmy) were observed, resulting in a rate of 0.058 mutations/site/million years (95% CI 0.031-0.108). These mutation rates are approximately 16 times higher than estimates derived from phylogenetic analysis with heteroplasmy detected in 13 samples (n = 225, 5.8% individuals). Providing one of the first pedigree derived estimates for the entire mtGenome, this study provides a better understanding of human mtGenome evolution and has relevance to many research fields, including medicine, anthropology and forensics.

Topical anaesthesia in neonatal circumcision: a study of 208 consecutive cases.

OBJECTIVE: To assess the suitability and effectiveness of EMLA cream (a eutectic mixture of lignocaine and prilocaine) as a topical anaesthetic for routine neonatal circumcision. DESIGN: A clinical trial of EMLA cream was conducted on 208 consecutive routine neonatal circumcisions. All circumcisions were performed by the Plastibell technique with prior use of EMLA anaesthetic cream. Results were obtained by intra-operative observation and follow-up questionnaire answered by parents. RESULTS: There was a marked decrease in crying during the procedure. In infants under the age of 7 months, 99.0% fed immediately, 96.0% settled rapidly and remained settled, 96.5% had no disturbance of sleep pattern, 92.5% had little or no pain and 96.0% had no pain or difficulty when urinating. None required stronger analgesia than paracetamol. Infants over the age of 7 months had more difficulty settling; however, their discomfort was no different from that seen in infants of similar age who were circumcised using general anaesthesia. There were no 'serious' complications and only 3.5% had minor complications. There were no side effects or complications attributable to the EMLA cream. CONCLUSION: EMLA anaesthetic cream, properly applied, is a safe and effective method of anaesthesia for circumcision of neonates to 7 months of age. It reduces or eliminates pain, restlessness, agitation and interference with parent bonding. The common practice (in Australia) of suggesting that parents postpone circumcision until the child is suitable for general anaesthesia should be seriously questioned.