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

The cleavage specificity of an IgA1 protease from Haemophilus influenzae

Bacterial IgA1 proteases are thought to be important virulence factors in respiratory tract infections. These proteolytic enzymes specifically cleave one of several post-proline peptide bonds within the hinge region of human immunoglobulin A1 (IgA1). Human IgA1 was cleaved with an IgA1 protease purified from an isolate of non-typeable Haemophilus influenzae (NTHI) and cleavage products were N-terminally sequenced. Cleavage of human IgA1 produced two different sized Fc fragments and N terminal sequencing of both these fragments revealed the sequence -Thr-Pro-Ser-Pro-Ser. The IgA1 protease could produce this double cleavage or it is possible that the bacterial strain of the NTHI could be producing two different IgA1 proteases simultaneously. However, PCR with sequence-specific primers amplified only one sequence of the IgA1 protease gene confirming that the NTHI isolate contained one iga gene, which would code for one IgA1 protease. Thus, one isolate of NTHI, which contains one iga gene sequence has been found to produce an IgA1 protease that cleaves two peptide bonds within the human IgA1 hinge region at replicate sequences. The iga gene sequence determines the unique cleavage specificity of the NTHI IgA1 protease and affects the inhibition of the protease. Further work will be required in order to design specific inhibitors to this important class of proteolytic enzymes