Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease.

Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD), surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease.A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist.Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2), cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25). The most frequent diagnosis was usual interstitial pneumonia (UIP) (n = 7). Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications.In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield

Safety outcomes.

<p>Data are presented as number of subjects or mean (range) where appropriate.</p

Biopsy characteristics.

<p>Data are presented as mean and range or mean and standard deviation where appropriate. Biopsy location is reported per subject. Percentages are calculated relative to total number of clinical biopsy subjects (n = 25).</p

Subject characteristics.

<p>Mean (range) or number (percentage) are presented as appropriate for demographic information. Pulmonary function tests are reported as mean (standard deviation). DLCO is reported corrected for hemoglobin when available.</p

Bronchoscopic cryobiopsy identifies characteristic histopathology from multiple DPLDs.

<p>Representative hematoxylin and eosin stained cryobiopsies from subjects with cryptogenic organizing pneumonia (A) 100x and (B) 400×, (C) bronchiolitis obliterans (200×), (D–E) respiratory bronchiolitis-interstial lung disease/desquamative interstitial pneumonia(100×) and (F) adenocarcinoma with lepidic spread, previously bronchoalveolar cell carcinoma (100×). Power reported as original magnification.</p

Bronchoscopic cryoprobe and low power images of biopsies demonstrate cryobiopsies are larger than typical forceps biopsies.

<p>(A) Bronchoscopic cryoprobe. (B) Gross pathology of a representative cryobiopsy specimen measuring 19 mm in length. (C) Typical transbronchial forceps biopsy. (D)) Normal bronchoscopic cryobiopsy sample. All images were taken at low power (40×).</p

Distribution of diagnoses made by bronchoscopic cryobiopsy in 25 clinical subjects.

<p>Abbreviations: UIP/IPF, usual interstitial pneumonia/idiopathic pulmonary fibrosis; OP, organizing pneumonia; RBILD/DIP, respiratory bronchiolitis-interstitial lung disease/desquamative interstitial pneumonia; HP, hypersensitivity pneumonitis; CB, constrictive bronchiolitis.</p