Open Access Open Badges Research article

Finished sequence and assembly of the DUF1220-rich 1q21 region using a haploid human genome

Majesta O’Bleness1, Veronica B Searles1, C Michael Dickens1, David Astling1, Derek Albracht2, Angel C Y Mak3, Yvonne Y Y Lai3, Chin Lin3, Catherine Chu3, Tina Graves2, Pui-Yan Kwok3, Richard K Wilson2 and James M Sikela1*

Author Affiliations

1 Department of Biochemistry and Molecular Genetics, Human Medical Genetics and Neuroscience Programs, University of Colorado School of Medicine, 12801 E. 17th Avenue, Aurora, CO 80045, USA

2 The Genome Institute at Washington University School of Medicine, St. Louis, MO 63108, USA

3 Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA

For all author emails, please log on.

BMC Genomics 2014, 15:387  doi:10.1186/1471-2164-15-387

Published: 20 May 2014



Although the reference human genome sequence was declared finished in 2003, some regions of the genome remain incomplete due to their complex architecture. One such region, 1q21.1-q21.2, is of increasing interest due to its relevance to human disease and evolution. Elucidation of the exact variants behind these associations has been hampered by the repetitive nature of the region and its incomplete assembly. This region also contains 238 of the 270 human DUF1220 protein domains, which are implicated in human brain evolution and neurodevelopment. Additionally, examinations of this protein domain have been challenging due to the incomplete 1q21 build. To address these problems, a single-haplotype hydatidiform mole BAC library (CHORI-17) was used to produce the first complete sequence of the 1q21.1-q21.2 region.


We found and addressed several inaccuracies in the GRCh37sequence of the 1q21 region on large and small scales, including genomic rearrangements and inversions, and incorrect gene copy number estimates and assemblies. The DUF1220-encoding NBPF genes required the most corrections, with 3 genes removed, 2 genes reassigned to the 1p11.2 region, 8 genes requiring assembly corrections for DUF1220 domains (~91 DUF1220 domains were misassigned), and multiple instances of nucleotide changes that reassigned the domain to a different DUF1220 subtype. These corrections resulted in an overall increase in DUF1220 copy number, yielding a haploid total of 289 copies. Approximately 20 of these new DUF1220 copies were the result of a segmental duplication from 1q21.2 to 1p11.2 that included two NBPF genes. Interestingly, this duplication may have been the catalyst for the evolutionarily important human lineage-specific chromosome 1 pericentric inversion.


Through the hydatidiform mole genome sequencing effort, the 1q21.1-q21.2 region is complete and misassemblies involving inter- and intra-region duplications have been resolved. The availability of this single haploid sequence path will aid in the investigation of many genetic diseases linked to 1q21, including several associated with DUF1220 copy number variations. Finally, the corrected sequence identified a recent segmental duplication that added 20 additional DUF1220 copies to the human genome, and may have facilitated the chromosome 1 pericentric inversion that is among the most notable human-specific genomic landmarks.

1q21; DUF1220 domain; Hydatidiform mole