A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements

Background: Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Case presentation: Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. Conclusions: To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single-nucleotide polymorphism probes with further analyses of the breakpoint junctions are recommended in cases suspected of having complex chromosomal abnormalities based on discrepancies between clinical and conventional cytogenetic findings

Suicide ideation of individuals in online social networks

Suicide explains the largest number of death tolls among Japanese adolescents in their twenties and thirties. Suicide is also a major cause of death for adolescents in many other countries. Although social isolation has been implicated to influence the tendency to suicidal behavior, the impact of social isolation on suicide in the context of explicit social networks of individuals is scarcely explored. To address this question, we examined a large data set obtained from a social networking service dominant in Japan. The social network is composed of a set of friendship ties between pairs of users created by mutual endorsement. We carried out the logistic regression to identify users' characteristics, both related and unrelated to social networks, which contribute to suicide ideation. We defined suicide ideation of a user as the membership to at least one active user-defined community related to suicide. We found that the number of communities to which a user belongs to, the intransitivity (i.e., paucity of triangles including the user), and the fraction of suicidal neighbors in the social network, contributed the most to suicide ideation in this order. Other characteristics including the age and gender contributed little to suicide ideation. We also found qualitatively the same results for depressive symptoms.Comment: 4 figures, 9 table

Examples of the degree () and the local clustering coefficient ().

<p>The shown values of and are for the nodes shown by the filled circles.</p

Univariate logistic regression of depressive symptoms on individual and network variables.

<p>OR: odds ratio; CI: 95% confidence interval; AUC: area under the curve.</p