The diploid nature of the human genome was first observed as unbanded and banded chromosomes over 40 years ago, and karyotyping still predominates in clinical laboratories as the standard for global genome interrogation. As such, the human genome functions as a diploid entity with phenotypes arising due to the sometimes complex interplay of alleles of genes and/or their noncoding functional regulatory elements. LF is supported by CIHR scholarship.Ĭompeting interests: The authors have declared that no competing interests exist.Ĭomparative genomic hybridization CHB+JPT,Įach of our genomes is typically composed of DNA packaged into two sets of 23 chromosomes one set inherited from each parent whose own DNA is a mosaic of preceding ancestors. SWS is an Investigator of the Canadian Institutes of Health Research (CIHR) and a Fellow of the Canadian Institute for Advanced Research. Craig Venter Institute, Genome Canada/Ontario Genomics Institute, The Hospital for Sick Children Foundation, the McLaughlin Centre for Molecular Medicine, and the Canada Foundation for Innovation. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: Funding was provided from the J. Received: Accepted: JPublished: September 4, 2007Ĭopyright: © 2007 Levy et al. Rubin, Lawrence Berkeley National Laboratories, United States of America PLoS Biol 5(10):Īcademic Editor: Edward M. (2007) The Diploid Genome Sequence of an Individual Human. The existence of a well-characterized diploid human genome sequence provides a starting point for future individual genome comparisons and enables the emerging era of individualized genomic information.Ĭitation: Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, et al. Inclusion of insertion and deletion genetic variation into our estimates of interchromosomal difference reveals that only 99.5% similarity exists between the two chromosomal copies of an individual and that genetic variation between two individuals is as much as five times higher than previously estimated. However, the results also reveal that lesser-studied genomic variants, insertions and deletions, while comprising a minority (22%) of genomic variation events, actually account for almost 74% of variant nucleotides. Comparison with previous reference human genome sequences, which were composites comprising multiple humans, revealed that the majority of genomic alterations are the well-studied class of variants based on single nucleotides (SNPs). Our approach, based on whole-genome shotgun sequencing and using enhanced genome assembly strategies and software, generated an assembled genome over half of which is represented in large diploid segments (>200 kilobases), enabling study of the diploid genome. We have generated an independently assembled diploid human genomic DNA sequence from both chromosomes of a single individual (J. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. Moreover, 44% of genes were heterozygous for one or more variants. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. Presented here is a genome sequence of an individual human.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |