The sequence of the human genome.
Level 5 - mechanism / opinion, no new human data
Level 5 by design analogy (laboratory genomic sequencing and descriptive bioinformatics assembly).
PubMed 11181995 · doi:10.1126/science.1058040
What was done
Researchers performed whole-genome shotgun sequencing on plasmid clone DNA obtained from five individuals, producing 27,271,853 high-quality reads (5.11-fold coverage). These reads were combined with shredded publicly funded sequence data (550-bp segments providing 2.9-fold coverage) to reach 8-fold effective assembly coverage. Sequences were assembled using two strategies: whole-genome assembly and regional chromosome assembly, followed by computational gene prediction and single-nucleotide polymorphism (SNP) identification.
What was found
The assembly yielded a 2.91-billion base pair (bp) consensus sequence covering the euchromatic genome, with over 90% of the genome residing in scaffolds of at least 100,000 bp and 25% in scaffolds of 10 million bp or larger. The sequence revealed 26,588 protein-encoding transcripts with strong corroborating evidence and approximately 12,000 additional computationally derived genes. Exons comprised 1.1% of the genome, introns spanned 24%, and 75% was intergenic. Comparison across sequences identified 2.1 million SNPs, with random haploid genomes differing at an average rate of 1 bp per 1,250 bp, and fewer than 1% of SNPs leading to protein coding variations.
Why it matters
This study provided the first published whole-genome shotgun assembly and gene catalog of the human genome, establishing a foundational reference sequence and identifying millions of polymorphism markers for genetics research.
Limits
The sequence covered only euchromatic regions, leaving gaps and omitting heterochromatic regions. Genomic DNA was derived from only five individuals, limiting population-wide diversity. Functional validation was absent for approximately 12,000 predicted genes, and the phenotypic consequences of the identified SNPs were not determined.
Cited by
- supports The human genome was sequenced in 2001.