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

Risk of Hepatobiliary and Pancreatic Cancers After Hepatitis C Virus Infection: A Population-Based Study of US Veterans

Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer. We conducted a cohort study including 146,394 HCV-infected and 572,293 HCV-uninfected patients who received care at Veterans Affairs health care facilities. Patients with two visits between 1996 and 2004 with HCV infection were included, as were up to four matched HCV-uninfected subjects for each HCV-infected subject. Risks of ICC, ECC, pancreatic cancer, and HCC were assessed using proportional hazards regression. In the 1.37 million person-years of follow-up, which began 6 months after the baseline visit, there were 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC. As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR], 15.09; 95% confidence interval [95% CI], 13.44, 16.94). Risk for ICC was elevated with HCV infection 2.55; 1.31, 4.95), but risk for ECC was not significantly increased (1.50; 0.60, 1.85). Adjustments for cirrhosis, diabetes, inflammatory bowel disease, hepatitis B, alcoholism, and alcoholic liver disease did not reduce the risk for ICC below twofold. The risk of pancreatic cancer was slightly elevated (1.23; 1.02, 1.49), but was attenuated after adjusting for alcohol use, pancreatitis, and other variables. Conclusions. Findings indicated that HCV infection conferred a more than twofold elevated risk of ICC. Absence of an association with ECC was consistent in adjusted and unadjusted models. A significant association with pancreatic cancer was erased by alcohol use and other variables. (HEPATOLOGY 2009;49:116-123.