The origin and significance of additional aneuploidy events in couples undergoing preimplantation genetic diagnosis for translocations by array comparative genomic hybridization

Diagnostic application of array comparative genomic hybridization (aCGH) in preimplantation genetic diagnosis for reciprocal and Robertsonian translocations has revealed 55–65% embryos with additional aneuploidies with or without translocation-related imbalances. The occurrence of these extra abnormalities with the balanced form of the translocation reduces the number of embryos suitable for transfer. Eighty-three embryos were followed up on days 5–7 of development from 23 infertile or sub-fertile carriers for whole chromosome and segmental aneuploidies present in addition to the balanced or unbalanced translocations detected on aCGH diagnosis. Embryos were analysed by fluorescence in-situ hybridization (n = 63) and aCGH (n = 20). Meiotic aneuploidy affected 35% of embryos and 47% had mitotic events; 15% had both types. Meiotic and mitotic events were almost equal (60 versus 64), 97 affected whole chromosomes (58 meiotic, 39 mitotic) and 27 were segmental (two meiotic, 25 mitotic). In 85.5% of embryos with whole chromosome additional aneuploidies, the aneuploidy was present throughout or in more than 50% of cells. All embryos diagnosed as abnormal (translocation balanced or unbalanced) after aCGH diagnosis at cleavage stage would have remained unsuitable for transfer if tested at later stages of development. Additional aneuploidies merit full consideration when considering the choice of embryos to transfer

Bioinformatic analysis of microduplications at 5p15.33: identification of TPPP as a candidate gene for autism and intellectual disability

Theidentification of candidate genes by bioinformatic analysis of recurrent copy number variations (CNV) (5p15.33 duplications) revealed by molecular karyotyping in a clinical cohor

In Mice, Tuberculosis Progression Is Associated with Intensive Inflammatory Response and the Accumulation of Gr-1dim Cells in the Lungs

Infection with Mycobacterium tuberculosis (Mtb) results in different clinical outcomes ranging from asymptomatic containment to rapidly progressing tuberculosis (TB). The mechanisms controlling TB progression in immunologically-competent hosts remain unclear.To address these mechanisms, we analyzed TB progression in a panel of genetically heterogeneous (A/SnxI/St) F2 mice, originating from TB-highly-susceptible I/St and more resistant A/Sn mice. In F2 mice the rates of TB progression differed. In mice that did not reach terminal stage of infection, TB progression did not correlate with lung Mtb loads. Nor was TB progression correlated with lung expression of factors involved in antibacterial immunity, such as iNOS, IFN-gamma, or IL-12p40. The major characteristics of progressing TB was high lung expression of the inflammation-related factors IL-1beta, IL-6, IL-11 (p<0.0003); CCL3, CCL4, CXCL2 (p<0.002); MMP-8 (p<0.0001). The major predictors of TB progression were high expressions of IL-1beta and IL-11. TNF-alpha had both protective and harmful effects. Factors associated with TB progression were expressed mainly by macrophages (F4-80(+) cells) and granulocytes (Gr-1(hi)/Ly-6G(hi) cells). Macrophages and granulocytes from I/St and A/Sn parental strains exhibited intrinsic differences in the expression of inflammatory factors, suggesting that genetically determined peculiarities of phagocytes transcriptional response could account for the peculiarities of gene expression in the infected lungs. Another characteristic feature of progressing TB was the accumulation in the infected lungs of Gr-1(dim) cells that could contribute to TB progression.In a population of immunocompetent hosts, the outcome of TB depends on quantitatively- and genetically-controlled differences in the intensity of inflammatory responses, rather than being a direct consequence of mycobacterial colonization. Local accumulation of Gr-1(dim) cells is a newly identified feature of progressing TB. High expression of IL-1beta and IL-11 are potential risk factors for TB progression and possible targets for TB immunomodulation