A century of genetic analysis has revealed that multiple mechanisms control the distribution of meiotic crossover events. In Drosophila melanogaster, two significant positional controls are interference and the strongly polar centromere effect. Here, we assess the factors controlling the distribution of crossovers (COs) and noncrossover gene conversions (NCOs) along all five major chromosome arms in 196 single meiotic divisions to generate a more detailed understanding of these controls on a genome-wide scale. Analyzing the outcomes of single meiotic events allows us to distinguish among different classes of meiotic recombination. In so doing, we identified 291 NCOs spread uniformly among the five major chromosome arms and 541 COs (including 52 double crossovers and one triple crossover). We find that unlike COs, NCOs are insensitive to the centromere effect and do not demonstrate interference. Although the positions of COs appear to be determined predominately by the long-range influences of interference and the centromere effect, each chromosome may display a different pattern of sensitivity to interference, suggesting that interference may not be a uniform global property. In addition, unbiased sequencing of a large number of individuals allows us to describe the formation of de novo copy number variants, the majority of which appear to be mediated by unequal crossing over between transposable elements. This work has multiple implications for our understanding of how meiotic recombination is regulated to ensure proper chromosome segregation and maintain genome stability.
Balancer chromosomes are multiply inverted chromosomes that suppress meiotic crossing over and prevent the recovery of crossover products. Balancers are commonly used in Drosophila melanogaster to maintain deleterious alleles and in stock construction. They exist for all three major chromosomes, yet the molecular location of the breakpoints and the exact nature of many of the mutations carried by the second and third chromosome balancers has not been available. Here, we precisely locate eight of 10 of the breakpoints on the third chromosome balancer TM3, six of eight on TM6, and nine of 11 breakpoints on TM6B. We find that one of the inversion breakpoints on TM3 bisects the highly conserved tumor suppressor gene p53—a finding that may have important consequences for a wide range of studies in Drosophila. We also identify evidence of single and double crossovers between several TM3 and TM6B balancers and their normal-sequence homologs that have created genetic diversity among these chromosomes. Overall, this work demonstrates the practical importance of precisely identifying the position of inversion breakpoints of balancer chromosomes and characterizing the mutant alleles carried by them.
Tibial plateau fractures are debilitating injuries. They can occurin younger individuals who sustain a high energy trauma or, withincreasing age, lesser degrees of trauma and underlying bone pathology such as osteoporosis, metabolic bone disease, and malignancy.1Outside these cases, tibial plateau fractures are relatively uncommon.However, these fractures can occur in healthy patients who have sustained direct trauma to the knee.Fractures of the tibial plateau often are classified according to theSchatzker or AO classification systems.2,3 These systems evaluate theinvolvement of both the medial and lateral plateaus, degree of comminution, extension into the joint, and displacement (both articularsurfaces and the relationship of the diaphysis to the metaphysis).Most tibial plateau fractures occur in the lateral aspect of the tibialplateau.1 The increased frequency of lateral fractures is due to themedial tibial plateau being able to resist higher weight-bearing loaddue to the presence of more cancellous bone. More importantly, thelateral plateau has more articular surface exposed during extensioncompared to the medial plateau, which increases likelihood of injury.4The standard of care for most displaced tibial plateau fracturesis surgical management with open reduction and internal fixation(ORIF).5 Conservative management, such as leg bracing, is an optionfor fractures that are nondisplaced or in patients too fragile for surgical intervention. In the senior population, a total knee arthroplasty(TKA) is a less common option. Tibial plateau fractures, particularlymedial tibial plateau fractures, caused by direct trauma in the elderly,non-osteoporotic population are uncommon.We present the case of an active male without overt risk for severefracture (10-year fracture risk of 10% via FRAX score) who wasworking to repair a trail in the Rocky Mountains. While other injurieswere more likely given the mechanism of injury and patient risk, thiscase highlighted the importance of considering tibial plateau fracture,even in atypical settings without significant risk. Improved awarenessof this mechanism of injury will lead to more accurate diagnosis andgreater post-injury management.
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