A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion
of the human genome was generated by the whole-genome shotgun sequencing m
ethod. The 14.8-billion bp DNA sequence was generated over 9 months from 27
,271,853 high-quality sequence reads (5.11-fold coverage of the genome) fro
m both ends of plasmid clones made from the DNA of five individuals. Two as
sembly strategies-a whole-genome assembly and a regional chromosome assembl
y-were used, each combining sequence data from Celera and the publicly fund
ed genome effort. The public data were shredded into 550-bp segments to cre
ate a 2.9-fold coverage of those genome regions that had been sequenced, wi
thout including biases inherent in the cloning and assembly procedure used
by the publicly funded group. This brought the effective coverage in the as
semblies to eightfold, reducing the number and size of gaps in the final as
sembly over what would be obtained with 5.11-fold coverage. The two assembl
y strategies yielded very similar results that Largely agree with independe
nt mapping data. The assemblies effectively cover the euchromatic regions o
f the human chromosomes. More than 90% of the genome is in scaffold assembl
ies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 mill
ion bp or larger. Analysis of the genome sequence revealed 26,588 protein-e
ncoding transcripts for which there was strong corroborating evidence and a
n additional similar to 12,000 computationally derived genes with mouse mat
ches or other weak supporting evidence. Although gene-dense clusters are ob
vious, almost half the genes are dispersed in Low G+C sequence separated by
large tracts of apparently noncoding sequence. Only 1.1% of the genome is
spanned by exons, whereas 24% is in introns, with 75% of the genome being i
ntergenic DNA. Duplications of segmental blocks, ranging in size up to chro
mosomal Lengths, are abundant throughout the genome and reveal a complex ev
olutionary history. Comparative genomic analysis indicates vertebrate expan
sions of genes associated with neuronal function, with tissue-specific deve
lopmental regulation, and with the hemostasis and immune systems. DNA seque
nce comparisons between the consensus sequence and publicly funded genome d
ata provided locations of 2.1 million single-nucleotide polymorphisms (SNPs
). A random pair of human haploid genomes differed at a rate of 1 bp per 12
50 on average, but there was marked heterogeneity in the Level of polymorph
ism across the genome. Less than 1% of all SNPs resulted in variation in pr
oteins, but the task of determining which SNPs have functional consequences
remains an open challenge.