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

Positional cloning of the Fanconi anaemia group A gene

The Fanconi anaemia/Breast cancer consortium* Fanconi anaemia (FA) is an autosomal recessive disorder associated with progressive bone-marrow failure, a variety of congenital abnormalities, and predisposition to acute myeloid leukaemia1. Cells from FA patients show increased sensitivity to bifunctional DNA crosslinking agents such as diepoxybutane and mitomycin C, with characteristic chromosome breakage2. FA is genetically heterogeneous, at least five different complementation groups (FA-A to FA-E) having been described3,4. The gene for group C (FAC) was cloned by functional complementation and mapped to chromosome 9q22.3 (refs 3, 5), but the genes for the other complementation groups have not yet been identified. The group A gene (FAA) has recently been mapped to chromosome 16q24.3 by linkage analysis6, and accounts for 60−65% of FA cases7,8. We narrowed the candidate region by linkage and allelic association analysis, and have isolated a gene that is mutated in FA-A patients. The gene encodes a protein of 1,455 amino acids that has no significant homology to any other known proteins, and may therefore represent a new class of genes associated with the prevention or repair of DNA damage.Sinoula Apostolou, Scott A. Whitmore, Joanna Crawford, Gregory Lennon, Grant R. Sutherland, David F. Callen, Leonarda lanzano, Maria Savino, Maria D'Apolito, Angelo Notarangeio, Elena Memeo, Maria Rosaria Piemontese, Leopoldo Zelante, Anna Savoia, Rachel A. Gibson, Alex J. Tipping, Neil V. Morgan, Sheila Hassock, Stander Jansen, Thomy J. de Ravel, Carola Van Berkell, Jan C. Pronk, Douglas F. Easton, Christopher G. Mathew, Orna Levran, Peter C. Verlander, Sat Dev Batish, Tamar Erlich, Arleen D. Auerbach, Anne-Marie Cleton-Jansen, Elna W. Moerland, Cees J. Cornelisse, Norman A. Doggett, Larry L. Deaven & Robert K. Moyzishttp://www.ncbi.nlm.nih.gov/pubmed/889656

The sequence and analysis of duplication rich human chromosome 16

We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility

The sequence and analysis of duplication-rich human chromosome 16

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.Joel Martin, Cliff Han, Laurie A. Gordon, Astrid Terry, Shyam Prabhakar, Xinwei She, Gary Xie, Uffe Hellsten, Yee Man Chan, Michael Altherr, Olivier Couronne, Andrea Aerts, Eva Bajorek, Stacey Black, Heather Blumer, Elbert Branscomb, Nancy C. Brown, William J. Bruno, Judith M. Buckingham, David F. Callen, Connie S. Campbell, Mary L. Campbell, Evelyn W. Campbell, Chenier Caoile, Jean F. Challacombe, Leslie A. Chasteen, Olga Chertkov, Han C. Chi, Mari Christensen, Lynn M. Clark, Judith D. Cohn, Mirian Denys, John C. Detter, Mark Dickson, Mira Dimitrijevic-Bussod, Julio Escobar, Joseph J. Fawcett, Dave Flowers, Dea Fotopulos, Tijana Glavina, Maria Gomez, Eidelyn Gonzales, David Goodstein, Lynne A. Goodwin, Deborah L. Grady, Igor Grigoriev, Matthew Groza, Nancy Hammon, Trevor Hawkins, Lauren Haydu, Carl E. Hildebrand, Wayne Huang, Sanjay Israni, Jamie Jett, Phillip B. Jewett, Kristen Kadner, Heather Kimball, Arthur Kobayashi, Marie-Claude Krawczyk, Tina Leyba, Jonathan L. Longmire, Frederick Lopez, Yunian Lou, Steve Lowry, Thom Ludeman, Chitra F. Manohar, Graham A. Mark, Kimberly L. McMurray, Linda J. Meincke, Jenna Morgan, Robert K. Moyzis, Mark O. Mundt, A. Christine Munk, Richard D. Nandkeshwar, Sam Pitluck, Martin Pollard Paul Predki, Beverly Parson-Quintana, Lucia Ramirez, Sam Rash, James Retterer, Darryl O. Ricke, Donna L. Robinson, Alex Rodriguez, Asaf Salamov, Elizabeth H. Saunders, Duncan Scott, Timothy Shough, Raymond L. Stallings, Malinda Stalvey, Robert D. Sutherland, Roxanne Tapia, Judith G. Tesmer, Nina Thayer, Linda S. Thompson, Hope Tice, David C. Torney, Mary Tran-Gyamfi, Ming Tsai, Levy E. Ulanovsky, Anna Ustaszewska, Nu Vo, P. Scott White, Albert L. Williams, Patricia L. Wills, Jung-Rung Wu, Kevin Wu, Joan Yang, Pieter DeJong, David Bruce, Norman A. Doggett, Larry Deaven, Jeremy Schmutz, Jane Grimwood, Paul Richardson, Daniel S. Rokhsar, Evan E. Eichler, Paul Gilna, Susan M. Lucas, Richard M. Myers, Edward M. Rubin and Len A. Pennacchi