RESUMEN
Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.
Asunto(s)
ADN/química , Genoma Humano , Análisis por Micromatrices , Análisis de Secuencia de ADN/métodos , Secuencia de Bases , Biología Computacional , Costos y Análisis de Costo , ADN/genética , Bases de Datos de Ácidos Nucleicos , Biblioteca Genómica , Genotipo , Haplotipos , Proyecto Genoma Humano , Humanos , Masculino , Nanoestructuras , Nanotecnología , Técnicas de Amplificación de Ácido Nucleico , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/economía , Análisis de Secuencia de ADN/instrumentación , Análisis de Secuencia de ADN/normas , Programas InformáticosRESUMEN
We describe a 14-year-old Hispanic boy who presented with a 2-month history of enlarging plum-colored cutaneous tumors on his face, trunk, and proximal extremities. Histopathologic examination showed nodular infiltrates of malignant mononuclear cells extending from the superficial dermis to the deep subcutis. Immunohistochemical staining of the biopsy specimen and flow cytometry studies on a bone marrow aspirate revealed a CD4+, CD56+ hematolymphoid tumor that was negative for all other myeloid and lymphoid markers. Based on this information, the patient was diagnosed with the recently described, rare non-T, non-B, nonmyeloid CD4+ CD56+ hematolymphoid malignancy. To our knowledge, this is the youngest patient reported in the literature.