From: Human genetics and genomics a decade after the release of the draft sequence of the human genome
Year | Development | References |
---|---|---|
1977 | Sanger dideoxynucleotide/chain termination sequencing method developed | [38] |
 | Mammalian genes shown to contain introns | [50] |
1978 | First report of characterisation of gross gene deletions responsible for human inherited disease (α- and β-thalassaemia) by Southern blotting | [51] |
1979 | First single base-pair substitution causing a human inherited disease (β-thalassaemia) characterized by DNA sequencing | [52] |
1980 | Construction of a genetic linkage map in humans using restriction fragment length polymorphisms | [53] |
1990 | Initiation of the Human Genome Project (HGP) | [54] |
1992 | Second-generation linkage map of the human genome | [55] |
1996 | The Human Gene Mutation Database (HGMD), an attempt to collate known (published) gene lesions responsible for human inherited disease, established and made available at http://www.hgmd.org | [56] |
 | Genome-wide association studies (GWAS) approach for genetic studies of complex diseases first proposed | [57] |
2001 | Completion of draft DNA sequences of the human genome by the International Human Genome Sequencing Consortium (IHGSC) and Celera Genomics | |
 | International SNP Map Working Group identifies 1.42 million SNPs in the human genome | [58] |
 | Genetic architecture of complex diseases subjected to intense debate | |
 | Linkage disequilibrium (LD) patterns documented between SNPs in regions of the human genome | |
2003 | Initiation of the International HapMap Project | [63] |
 | First whole-genome SNP genotyping array - Affymetrix GeneChip 10K | [17] |
2004 | IHGSC publishes the 'finished version' of the DNA sequence of the human genome | [64] |
 | Initiation of the ENCODE project | [65] |
 | Discovery of hundreds of copy number variations (CNVs) in the human genome | |
 | Database of Genomic Variants (DGV) established to catalogue CNVs | [27] |
 | First new-generation sequencing (NGS) technology - Roche 454 GS 20 System | |
2005 | Completion of the International HapMap Phase I Project | [66] |
 | First proper GWAS using a commercial whole-genome SNP genotyping array | [3] |
2005-present | Rapid developments of whole-genome and custom SNP genotyping arrays and technologies | [18] |
 | Rapid developments of sequencing technologies | |
2006 | Discovery of more than 1,000 regions of homozygosity > 1 megabase (Mb) in the genomes of outbred populations | [28] |
 | First comprehensive map of CNVs in the HapMap populations | [22] |
 | An initial map of insertion and deletion variants in the human genome | [67] |
 | Illumina sequencing platform commercially marketed | |
2007 | The first human diploid genome (Craig Venter's genome) sequenced by the Sanger sequencing method | [68] |
 | Completion of the International HapMap Phase II Project and extension to Phase III | [69] |
 | Genome-wide detection and characterisation of positive selection in human populations | [70] |
 | Completion of the ENCODE project | [71] |
 | Explosion of GWAS publications ('Year of GWAS'), approximately 100 new GWASs | [4] |
 | 'Human Genetic Variation' considered to be the 'Breakthrough of The Year' in 2007 by Science | [4] |
 | Sequence capture or enrichment methods and technologies developed | |
 | Pervasive transcription documented | [75] |
 | Demonstration of paired-end mapping (PEM) to detect structural variation using NGS technologies | [76] |
 | Demonstration of ChIP-Seq to map transcription factor binding sites | [77] |
 | Demonstration of ChIP-Seq to interrogate histone modifications | [78] |
 | Life Technologies SOLiD sequencing platform commercially marketed | |
 | A community resource project launched to sequence large-insert clones from many individuals, systematically discovering and resolving these complex variants at the DNA sequence level (The Human Genome Structural Variation Working Group) | [79] |
2007-Present | Microarray-based methods increasingly supplanted by sequencing-based approaches such as ChIP-Seq, RNA-Seq, Methyl-Seq and CNV-Seq | |
2008 | First human diploid genome (James Watson's genome) sequenced by NGS technologies | [46] |
 | First whole cancer genome (acute myeloid leukaemia [AML]) sequenced | [82] |
 | Initiation of the 1000 Genomes Project | [83] |
 | Vast majority of human genes shown to undergo alternative splicing (RNA-Seq) | |
 | Large scale mapping and sequencing of structural variation using a clone-based method | [86] |
 | Demonstration of depth-of-coverage approach to detect CNVs using NGS technologies | [87] |
 | First GWAS meta-analysis using imputation methods | [88] |
 | The issue of 'missing heritability' in GWASs recognised | [89] |
2009 | Feasibility of exome sequencing approach to identify a causal mutation for a Mendelian disorder first demonstrated | [12] |
 | Exome sequencing as a useful tool for diagnostic application demonstrated | [90] |
 | Third generation sequencing (TGS; single molecule sequencing) technology introduced --Heliscope Single Molecule Sequencer (Helicos Biosciences) commercially marketed | [91] |
 | First human diploid genome sequenced by TGS technology | [92] |
 | Latest assembly of the human genome (Genome Reference Consortium, release GRCh37, February 2009), Genebuild published by Ensembl (database version 56.37a) includes 23,616 protein-coding genes, 6,407 putative RNA genes and 12,346 pseudogenes | |
 | Large intergenic non-coding RNAs (lincRNAs) found to represent a novel category of evolutionarily conserved RNAs | |
 | Direct single molecule RNA sequencing without prior conversion of RNA to cDNA | [95] |
 | First human DNA methylomes at base resolution | [96] |
 | Comprehensive mapping of long-range chromatin interactions | |
2010 | Number of disease-causing/disease-associated germline mutations collated in the Human Gene Mutation Database exceeds 100,000 in > 3,700 different nuclear genes | |
 | More than 17 million SNPs in the human genome catalogued in the SNP Database (dbSNP; http://www.ncbi.nlm.nih.gov/projects/SNP/) | [101] |
 | As of 2nd November 2010, DGV catalogued 66,741 CNVs, 953 inversions and 34,229 insertions and deletions (indels) (100 base pairs (bp) -- 1 kilobase (kb) from 42 published studies | |
 | 1,048 microRNAs found in the human genome | miRBase, Release 16.0: September 2010, http://www.mirbase.org/ |
 | Completion of the International HapMap Phase III Project | [21] |
 | Completion of pilot phase of the 1000 Genomes Project | [102] |
 | Second generation whole-genome SNP genotyping array (with SNP selection from the 1000 Genomes Project) launched | |
 | Cost of whole-genome sequencing (at several tenfold of sequencing coverage depth) reduced to less than $5,000 | [44] |
 | Metagenomic sequencing of human gut microbes accomplished using NGS technologies | [103] |
 | Exome sequencing study identifies causal mutations and genes for previously unexplained Mendelian disorders | |
 | GWAS meta-analysis involving total sample size of > 249,000 | [104] |
 | Comprehensive mapping of CNVs using high-resolution tiling oligonucleotide microarrays (42 million probes) | [105] |
 | Characterisation of 20 sequenced human genomes to evaluate the prospects for identifying rare functional variants | [106] |
 | Neanderthal genome sequenced | [107] |
 | The genome of an extinct Palaeo-Eskimo sequenced | [108] |
 | Exome sequencing of 200 individuals identifies an excess of low-frequency non-synonymous coding variants | [109] |
 | International Cancer Genome Consortium (ICGC) launched | [110] |
 | Largest GWAS of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls performed | [111] |
2011 | As of 13th May 2011, 874 publications and 4,327 SNPs documented in the National Human Genome Research Institute (NHGRI) 'A Catalog of Published Genome-wide Association Studies' | |
 | Comprehensive mapping of copy number variations based on whole-genome DNA sequencing data | [112] |
 | Developments of other TGS technologies, such as single-molecule real-time sequencing and nanopore sequencing, are on the horizon | [32] |
 | New addition to the NGS market -- the Ion Torrent Personal Genome Machine (PGM), produced by Life Technologies (Carlsbad, CA) | |
 | Single-cell sequencing to infer tumour evolution | [113] |