Detection and annotation of transposable element insertions and deletions on the human genome using nanopore sequencing.

Repetitive sequences represent about 45% of the human genome. Some are transposable elements (TEs) with the ability to change their position in the genome, creating genetic variability both as insertions or deletions, with potential pathogenic consequences. We used long-read nanopore sequencing to identify TE variants in the genomes of 24 patients with antithrombin deficiency. We identified 7 344 TE insertions and 3 056 TE deletions, 2 926 were not previously described in publicly available databases. The insertions affected 3 955 genes, with 6 insertions located in exons, 3 929 in introns, and 147 in promoters. Potential functional impact was evaluated with gene annotation and enrichment analysis, which suggested a strong relationship with neuron-related functions and autism. We conclude that this study encourages the generation of a complete map of TEs in the human genome, which will be useful for identifying new TEs involved in genetic disorders.

Gynaecological and obstetrical bleeding in Caucasian women with congenital factor XI deficiency: Results from a twenty-year, retrospective, observational study / Hemorragia ginecológica y obstétrica en mujeres caucásicas con deficiencia congénita de factor XI: Resultados de veinte años de registro observacional y retrospectivo

Introduction: Factor XI (FXI) deficiency is a mild bleeding disorder, common among Ashkenazis, that may be underestimated in Caucasians. Management of FXI deficiency in women is a challenge, due to its unpredictable bleeding tendency and the little evidence available on this issue. Objective: To describe gynaecological/obstetrical bleeding complications and to analyze the effectiveness and safety of the antihaemorrhagic treatment among women with FXI deficiency. Material and methods: A retrospective, observational study of 214 Caucasian subjects with FXI deficiency collected during 20 years (1994-2014) without clinical selection. Results: We identified 95 women with FXI deficiency. Any haemorrhagic event was communicated by 26/95 (27.4%), being abnormal uterine bleeding the most frequently found (12/95, 12.6%). Nine postpartum haemorrhages were recorded from 136 deliveries (6.6%) in 57 women. Four postsurgical bleeding complications were registered among 25 gynaecological surgeries (16%) in 20 women. Abnormal uterine bleeding, postpartum and postsurgical haemorrhages were related to both a positive bleeding history and FXI:C values ≤43.5%. Prophylaxis with fresh frozen plasma, used in 12/25 (48%) gynaecological surgeries, did not prevent from postoperative bleeding in three cases, but two developed severe adverse reactions. Conclusion: Women with FXI deficiency, especially those with a positive history of bleeding or FXI:C ≤43.5%, are at risk of developing gynaecological/obstetrical haemorrhages, most of them mild/moderate. Systematic prophylaxis has questionable effectiveness, but might cause severe side effects

Introducción: La deficiencia del factor XI (FXI) es un trastorno hemorrágico leve, común entre los asquenazíes, que puede subestimarse en los caucásicos. El manejo de la deficiencia de FXI en las mujeres es un desafío, debido a la dificultad para predecir la tendencia hemorrágica y la poca evidencia disponible sobre este tema. Objetivo: Describir las complicaciones hemorrágicas ginecológicas/obstétricas y analizar la efectividad y la seguridad del tratamiento antihemorrágico en mujeres con deficiencia de FXI. Material y métodos: Estudio observacional retrospectivo de 214 sujetos caucásicos con deficiencia de FXI recogidos durante 20 años (1994-2014) sin selección clínica. Resultados: Se identificaron 95 mujeres con deficiencia de FXI. Cualquier evento hemorrágico fue comunicado por 26/95 (27.4%), siendo la hemorragia uterina anormal el más frecuente (12/95, 12.6%). Se registraron nueve hemorragias posparto de 136 partos (6,6%) en 57 mujeres. Se registraron cuatro complicaciones hemorrágicas posquirúrgicas en 25 cirugías ginecológicas (16%) en 20 mujeres. La hemorragia uterina anormal y las hemorragias postparto y posquirúrgicas se relacionaron con una historia positiva para hemorragia y valores de FXI:C ≤ 43.5%. La profilaxis con plasma fresco congelado, utilizado en 12/25 (48%) cirugías ginecológicas, no evitó la hemorragia postoperatoria en tres casos, pero dos desarrollaron reacciones adversas graves. Conclusión: Las mujeres con deficiencia de FXI, especialmente aquellas con una historia positiva para hemorragia o FXI:C ≤ 43.5%, están en riesgo de desarrollar hemorragias ginecológicas/obstétricas, la mayoría de ellas leves/moderadas. La profilaxis sistemática tiene una efectividad cuestionable, pero puede causar efectos secundarios graves