The t(11;22) is the only known recurrent, non-Robertsonian constitutional translocation. We have analyzed t(11;22) balanced-translocation carriers from multiple unrelated families by FISH, to localize the t(11;22) breakpoints on both chromosome 11 and chromosome 22. In 23 unrelated balanced-translocation carriers, the breakpoint was localized within a 400-kb interval between D22S788 (N41) and ZNF74, on 22q11. Also, 13 of these 23 carriers were tested with probes from chromosome 11, and, in each, the breakpoint was localized between D11S1340 and APOA1, on 11q23, to a region =185 kb. Thus, the breakpoints on both chromosome 11 and chromosome 22 are clustered in multiple unrelated families. Supernumerary-der(22)t(11;22) syndrome can occur in the progeny of balanced-t(11;22) carriers, because of malsegregation of the der(22). There has been speculation regarding the mechanism by which the malsegregation occurs. To elucidate this mechanism, we have analyzed 16 of the t(11;22) families, using short tandem-repeat-polymorphism markers on both chromosome 11 and chromosome 22. In all informative cases the proband received two of three alleles, for markers above the breakpoint on chromosome 22 and below the breakpoint on chromosome 11, from the t(11;22)-carrier parent. These data strongly suggest that 3:1 meiosis I malsegregation in the t(11;22) balanced-translocation-carrier parent is the mechanism in all 16 families. Taken together, these results establish that the majority of t(11;22) translocations occur within the same genomic intervals and that the majority of supernumerary-der(22) offspring result from a 3:1 meiosis I malsegregation in the balanced-translocation carrier.
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http://dx.doi.org/10.1086/302666 | DOI Listing |
Mol Cell
January 2025
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address:
Unassembled and partially assembled subunits of multi-protein complexes have emerged as major quality control clients, particularly under conditions of imbalanced gene expression such as stress, aging, and aneuploidy. The factors and mechanisms that eliminate such orphan subunits to maintain protein homeostasis are incompletely defined. Here, we show that the UBR4-KCMF1 ubiquitin ligase complex is required for the efficient degradation of multiple unrelated orphan subunits from the chaperonin, proteasome cap, proteasome core, and a protein targeting complex.
View Article and Find Full Text PDFPLoS One
January 2025
Instituto René Rachou, Fiocruz Minas, Fundação Oswaldo Cruz (Fiocruz), Belo Horizonte, Minas Gerais, Brazil.
Background: To develop an effective vaccine against Plasmodium vivax, the most widely dispersed human malaria parasite, it is critical to understand how coinfections with other pathogens could impact malaria-specific immune response. A recent conceptual study proposed that Epstein-Barr virus (EBV), a highly prevalent human herpesvirus that establishes lifelong persistent infection, may influence P. vivax antibody responses.
View Article and Find Full Text PDFJAMA Dermatol
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Centre for Molecular Medicine and Biobanking, University of Malta, Malta.
Importance: Variation in nicastrin (NCSTN) is associated with a monogenic subtype of hidradenitis suppurativa. Dysregulation of humoral immunity has been suggested as a potential mechanistic link between NCSTN variation and hidradenitis suppurativa. There is a paucity of biomarkers that can predict disease-associated variation.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Urology, Vanderbilt University Medical Center, Nashville, USA.
Recent advancements of large language models (LLMs) like generative pre-trained transformer 4 (GPT-4) have generated significant interest among the scientific community. Yet, the potential of these models to be utilized in clinical settings remains largely unexplored. In this study, we investigated the abilities of multiple LLMs and traditional machine learning models to analyze emergency department (ED) reports and determine if the corresponding visits were due to symptomatic kidney stones.
View Article and Find Full Text PDFJ Assist Reprod Genet
January 2025
Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research Group Genetics, Reproduction and Development, Centre for Medical Genetics, Laarbeeklaan 101, 1090, Brussels, Belgium.
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