Next-generation sequencing-based genome diagnostics across clinical genetics centers: Implementation choices and their effects

Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome- and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care

Радиационная стойкость нитевидных кристаллов SiGe, используемых для сенсоров физических величин

Приведены результаты исследования влияния облучения γ-квантами дозами до 1·10¹⁸ см⁻² и магнитного поля с индукцией до 14 Тл на электропроводность нитевидных кристаллов Si1-xGex в интервале температуры 4,2-300 К.Вивчено вплив опромінення γ-квантами (випромінювання Co⁶⁰) з дозами до 1·10¹⁸ см⁻² та магнітного поля з індукцією до 14 Тл на електропровідність ниткоподібних кристалів Si1-xGex (х = 0,03) з питомим опором 0,08,0,025 Ом·см в інтервалі температур 4,2 .300 К. Встановлено, що опір кристалів слабо змінюється в процесі опромінення дозами до 2·10¹⁷ см⁻², в той же час спостерігаються істотні зміни магнітоопору. На основі проведених досліджень запропоновано умови створення радіаційно стійких сенсорів деформації, дієздатних в умовах сильних магнітних полів.An influence of γ-irradiation (Co⁶⁰) with doze up to 1·10¹⁸ cm⁻² and magnetic field with induction up to 14 T on conduction of Si1-xGex (x = 0,03) whisker crystals with resistivity of 0,08-0,025 Ohm·cm in temperature range 4,2-300 K have been studied. It is shown that whisker crystals resistance faintly varies under irradiation with doze 2·10¹⁷ cm⁻², while their magnetoresistance substantially changes. The strain sensors stable to irradiation action operating in high magnetic fields on the base of the whiskers have been designed