The DNA sequence and biology of human chromosome 19

Grimwood, Jane
Gordon, Laurie A.
Olsen, Anne
Terry, Astrid
Schmutz, Jeremy
Lamerdin, Jane
Hellsten, Uffe
Goodstein, David
Couronne, Olivier
Tran-Gyamfi, Mary
Aerts, Andrea
Altherr, Michael
Ashworth, Linda
Bajorek, Eva
Black, Stacey
Branscomb, Elbert
Caenepeel, Sean
Carrano, Anthony
Caoile, Chenier
Man Chan, Yee
Christensen, Mari
Cleland, Catherine A.
Copeland, Alex
Dalin, Eileen
Dehal, Paramvir
Denys, Mirian
Detter, John C.
Escobar, Julio
Flowers, Dave
Fotopulos, Dea
Garcia, Carmen
Georgescu, Anca M.
Glavina, Tijana
Gomez, Maria
Gonzales, Eidelyn
Groza, Matthew
Hammon, Nancy
Hawkins, Trevor
Haydu, Lauren
Ho, Isaac
Huang, Wayne
Israni, Sanjay
Jett, Jamie
Kadner, Kristen
Kimball, Heather
Kobayashi, Arthur
Larionov, Vladimer
Leem, Sun-Hee
Lopez, Frederick
Lou, Yunian
Lowry, Steve
Malfatti, Stephanie
Martinez, Diego
McCready, Paula
Medina, Catherine
Morgan, Jenna
Nelson, Kathryn
Nolan, Matt
Ovcharenko, Ivan
Pitluck, Sam
Pollard, Martin
Popkie, Anthony P.
Predki, Paul
Quan, Glenda
Ramirez, Lucia
Rash, Sam
Retterer, James
Rodriguez, Alex
Rogers, Stephanine
Salamov, Asaf
Salazar, Angelica
She, Xinwei
Smith, Doug
Slezak, Tom
Solovyev, Victor
Thayer, Nina
Tice, Hope
Tsai, Ming
Ustaszewska, Anna
Vo, Nu
Wagner, Mark
Wheeler, Jeremy
Wu, Kevin
Xie, Gary
Yang, Joan
Dubchak, Inna
Furey, Terrence S.
DeJong, Pieter
Dickson, Mark
Gordon, David
Eichler, Evan E.
Pennacchio, Len A.
Richardson, Paul
Stubbs, Lisa
Rokhsar, Daniel S.
Myers, Richard M.
Rubin, Edward M.
Lucas, Susan M.

¹Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, 975 California Avenue, Palo Alto, California 94304, USA
²DOE's Joint Genome Institute, 2800 Mitchell Avenue, Walnut Creek, California 94598, USA
³Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550, USA
⁴Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
⁵Laboratory of Biosystems and Cancer, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
⁶Department of Genetics, Center for Computational Genomics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA
⁷Center for Biomolecular Science and Engineering, University of California, Santa Cruz, California 95064, USA
⁸Children's Hospital Oakland, Oakland, California 94609, USA
⁹Howard Hughes Medical Institute at the Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA

Received 1 December 2003; accepted 10 February 2004; doi:10.1038/nature02399.

Supplementary Information accompanies the paper on www.nature.com/nature.

Correspondence and requests for materials should be addressed to J.G. ([email protected]) and E.M.R ([email protected]). The entire sequence for the chromosome is deposited in GenBank under accession numbers NT_00255, NT_ 077812, NT_011295 and NT_011109.

Nature 428(6982):p 529-535, April 1, 2004.

Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G+C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish speciesTakifugu.