Initial sequencing and analysis of the human genome

Nature, 2000

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNAPro genes and the other contains 27 tandem repeats of tRNATyr-tRNATyr-tRNASergenes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

The Indian Journal of Medical Research, 2003

The recent sequencing of the human genome, resulting from two independent global efforts, is poised to revolutionize all aspects of human health. This landmark achievement has also vindicated two different methodologies that can now be used to target other important large genomes. The human genome sequence has revealed several novel/surprising features notably the probable presence of a mere 30-35,000 genes. In depth comparisons have led to classification of protein families and identification of several orthologues and paralogues. Information regarding non-protein coding genes as well as regulatory regions has thrown up several new areas of research. Although still incomplete, the sequence is poised to become a boon to pharmaceutical companies with the promise of delivering several new drug targets. Several ethical concerns have also been raised and need to be addressed in earnest. This review discusses all these aspects and dwells on the possible impact of the human genome sequence on human health, medicine and also health care delivery system.

2005

Nature, 2002

After the initial assembly of sequence data, stretches of poor or ambiguous quality and apparent gap regions were identified for further sequencing to obtain greater than 99.99% sequence accuracy. But despite extensive efforts to improve the sequence quality and to fill the gaps, 4 of the 390 PAC/BAC clones sequenced are still at phase 1 (GenBank, http:// www.ncbi.nlm.nih.gov/HTGS/) because the consensus sequence could not be ordered correctly owing to numerous repeats. The remainder comprises 16 phase 2 and 370 phase 3 clones. The nine contigs for chromosome 1 representing the non-overlapping segments of continuous sequence were conjoined by inserting into the gap regions nucleotides that were calculated on the basis of the results of FISH experiments. All of the sequence information of chromosome 1 has been submitted to the DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp/) with the accession number BA000010 (Con Division).

PLoS Biology, 2003

Nature, 2000

We thank G. Copenhaver for his contribution to completing the chromosome; M. Marra and M. Sekhon for mapping data; J. Hazan, H. Roest Crollius and M. Katinka for discussions; and system administrators, sequencing facility, bioinformatics department and administrative staff from TIGR, Genoscope and Kazusa Institute.

Nature, 2004

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineageindependent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

Nucleic Acids Research, 2003

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcriptioncoupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational`hot' and`cold' regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.

Science, 2004

Nucleic Acids Research, 2002

A set of 22 551 unique human NotI¯anking sequences (16.2 Mb) was generated. More than 40% of the set had regions with signi®cant similarity to known proteins and expressed sequences. The data demonstrate that regions¯anking NotI sites are less likely to form nucleosomes ef®ciently and resemble promoter regions. The draft human genome sequence contained 55.7% of the NotI¯anking sequences, Celera's database contained matches to 57.2% of the clones and all public databases (including non-human and previously sequenced NotĪ anks) matched 89.2% of the NotI¯anking sequences (identity b90% over at least 50 bp, data from December 2001). The data suggest that the shotgun sequencing approach used to generate the draft human genome sequence resulted in a bias against cloning and sequencing of NotI¯anks. A rough estimation (based primarily on chromosomes 21 and 22) is that the human genome contains 15 000±20 000 NotI sites, of which 6000±9000 are unmethylated in any particular cell. The results of the study suggest that the existing tools for computational determination of CpG islands fail to identify a signi®cant fraction of functional CpG islands, and unmethylated DNA stretches with a high frequency of CpG dinucleotides can be found even in regions with low CG content.

Nature, 2003

The recent draft assembly of the human genome provides a unified basis for describing genomic structure and function. The draft is sufficiently accurate to provide useful annotation, enabling direct observations of previously inferred biological phenomena.

Rice, one of the world's most important food plants, has important syntenic relationships with the other cereal species and is a model plant for the grasses. Here we present a map-based, finished quality sequence that covers 95% of the 389 Mb genome, including virtually all of the euchromatin and two complete centromeres. A total of 37,544 nontransposable-element-related protein-coding genes were identified, of which 71% had a putative homologue in Arabidopsis. In a reciprocal analysis, 90% of the Arabidopsis proteins had a putative homologue in the predicted rice proteome. Twenty-nine per cent of the 37,544 predicted genes appear in clustered gene families. The number and classes of transposable elements found in the rice genome are consistent with the expansion of syntenic regions in the maize and sorghum genomes. We find evidence for widespread and recurrent gene transfer from the organelles to the nuclear chromosomes. The map-based sequence has proven useful for the identification of genes underlying agronomic traits. The additional single-nucleotide polymorphisms and simple sequence repeats identified in our study should accelerate improvements in rice production.

Cytogenetic and Genome Research, 2013

higher in embryonic tissues compared to placenta. The findings advance the knowledge about the comparative organization of the PAR in mammals and suggest that the region might have important functions in early development in pigs.