Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.

There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone-induced pancreatitis.Une hausse de l'incidence de pancréatite aiguë a été constatée à l'échelle mondiale. Malgré l'amélioration de l'accès aux soins et aux techniques d'imagerie et d'intervention, la pancréatite aiguë est toujours associée à une morbidité et une mortalité importantes. Bien qu'il existe des guides de pratique clinique pour la prise en charge de la pancréatite aiguë, des études récentes sur la vérification de la prise en charge clinique de cette affection révèlent des lacunes importantes dans la conformité aux recommandations fondées sur des données probantes. Ces résultats mettent en relief l'importance de formuler des recommandations compréhensibles et applicables pour le diagnostic et la prise en charge de la pancréatite aiguë. La présente ligne directrice vise à fournir des recommandations fondées sur des données probantes pour la prise en charge de la pancréatite aiguë, qu'elle soit bénigne ou grave, ainsi que de ses complications et de celles de la pancréatite causée par un calcul biliaire.A cute pancreatitis can range from a mild, self-limiting disease that requires no more than supportive measures to severe disease with lifethreatening complications. The most common causes of acute pan creatitis are gallstones and binge alcohol consumption.1 There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality.A systematic review of clinical practice guidelines for the management of acute pancreatitis revealed 14 guidelines published between 2004 and 2008 alone.2 Although these guidelines have significant overlap in their recommendations for diagnosing and managing acute pancreatitis, there is disagreement in some aspects of both the timing and types of interventions that should be used for both mild and severe acute pancreatitis. The availability of new imaging modalities and noninvasive therapies has also changed clinical practice. Finally, despite the availability of guidelines, recent studies auditing clinical management of acute pancreatitis have sh...