Mitochondrial DNA (mtDNA) is maternally inherited in mammals. Despite the high genome copy number in mature oocytes (10(5)) and the relatively small number of cell divisions in the female germline, mtDNA sequence variants segregate rapidly between generations. To investigate the molecular basis for this apparent paradox we created lines of heteroplasmic mice carrying two mtDNA genotypes. We show that the pattern of segregation can be explained by random genetic drift occurring in early oogenesis, and that the effective number of segregating units for mtDNA is approximately 200 in mice. These results provide the basis for estimating recurrence risks for mitochondrial disease due to pathogenic mtDNA mutations and for predicting the rate of fixation of neutral mtDNA mutations in maternal lineages.
Leigh Syndrome (LS) is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. COX deficiency is an autosomal recessive trait and most patients belong to a single genetic complementation group. DNA sequence analysis of the genes encoding the structural subunits of the COX complex has failed to identify a pathogenic mutation. Using microcell-mediated chromosome transfer, we mapped the gene defect in this disorder to chromosome 9q34 by complementation of the respiratory chain deficiency in patient fibroblasts. Analysis of a candidate gene (SURF1) of unknown function revealed several mutations, all of which predict a truncated protein. These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease.
The bridge between engineering design and cognitive science research is critical to understand the effectiveness of design methods as implemented by human designers. The study reported in this paper evaluates the effects of design fixation in a group of engineering design faculty, and also provides evidence for approaches to overcome design fixation. Three conditions are compared, a control, a fixation group whom were provided with an example solution, and a defixation group whom were also given materials to mitigate their design fixation. Measures include indicators of design fixation and participant perceptions. The study demonstrates that the engineering design faculty show statistically significant evidence of design fixation, but only partially perceive its effects. This study also indicates that design fixation can be mitigated. The group of participants in this study, due to their background in engineering design research and experience with student design teams, was expected to have more accurate perceptions or awareness of design fixation than the typical participant. Understanding the incongruities between participant perceptions and quantitative design outcomes are particularly of interest to researchers of design methods. For this study, clear evidence exists that designers, even those that study and teach design on a regular basis, do not know when they are being influenced or fixated by misleading or poor information.
Drawing inspiration from examples by analogy can be a powerful tool for innovative design during conceptual ideation but also carries the risk of negative design outcomes (e.g., design fixation), depending on key properties of examples. Understanding these properties is critical for effectively harnessing the power of analogy. The current research explores how variations in analogical distance, commonness, and representation modality influence the effects of examples on conceptual ideation. Senior-level engineering students generated solution concepts for an engineering design problem with or without provided examples drawn from the U.S. Patent database. Examples were crossed by analogical distance (near-field vs. far-field), commonness (more vs. less-common), and modality (picture vs. text). A control group that received no examples was included for comparison. Effects were examined on a mixture of ideation process and product variables. Our results show positive effects of far-field and less-common examples on novelty and variability in quality of solution concepts. These effects are not modulated by modality. However, detailed analyses of process variables suggest divergent inspiration pathways for far-field vs. less-common examples. Additionally, the combination of far-field, less-common examples resulted in more novel concepts than in the control group. These findings suggest guidelines for the effective design and implementation of design-by-analogy methods, particularly a focus on far-field, less-common examples during the ideation process.
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