Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas)

Chronic lymphocytic leukaemia, dyspnoea and “tree-in-bud” sign on chest CT scan

Chronic lymphocytic leukaemia (CLL) is a common disorder. Patients typically present with lymphadenopathy, splenomegaly and marked lymphocytosis (often >100 000/μl). Although pulmonary involvement from CLL can be found in more than one third of patients on autopsy, respiratory symptoms caused by the disease itself are not often reported. Pulmonary involvement mainly includes parenchymal infiltrates, peribronchial and perivascular infiltration, recurrent bacterial pneumonia, oedema or infarction, pleural effusions, and lymphadenopathy. Occasionally, patients may present with dry cough and progressive dyspnoea, even with low peripheral white blood cell count. We report a case of CLL and dyspnoea at rest, predominant “tree-in-bud” sign on chest computed tomography scan, and biopsy proven bronchiolar infiltration with monoclonal lymphocytes. With bronchoalveolar lavage alone, the diagnosis would have been missed. Chemotherapy with rituximab, cyclophosphamide, and fludarabinphosphate led to a prompt clinical and radiological improvement with a gain in 6 min walking distance from 60 to 210 m

An attempt to recover the Po'ouli by translocation and an appraisal of recovery strategy for bird species of extreme rarity

The Po'ouli (Melamprosops phaeosoma), a Hawaiian honeycreeper endemic to Maui, has a population of only three known individuals; no breeding pair currently exists, and their home ranges are too far apart for breeding to occur. Without timely intervention this monotypic genus will likely go extinct. Conservationists have faced a dilemma: facilitate breeding amongst the known individuals, manage their ecosystem to benefit uncounted Po'ouli, or a combination of both? Po'ouli biology is poorly known - but their remote home ranges are closely monitored. A State and Federal Environmental Assessment in 1999 recommended that one Po'ouli be translocated into the home range of another in an attempt to facilitate breeding. This first manipulative recovery action was achieved in April 2002, and provided valuable new information for future captive management efforts, but upon release, radio telemetry confirmed that the translocated bird returned to its own home range after one day. We describe the recent progress that has been made to recover the Po'ouli, and critically evaluate the Po'ouli case study and the lessons learned from it that can help expedite recovery of other birds of extreme rarity. (C) 2003 Elsevier Ltd. All rights reserved