Reference genome

Last updated
The first printout of the human reference genome presented as a series of books, displayed at the Wellcome Collection, London Wellcome genome bookcase.png
The first printout of the human reference genome presented as a series of books, displayed at the Wellcome Collection, London

A reference genome (also known as a reference assembly) is a digital nucleic acid sequence database, assembled by scientists as a representative example of the set of genes in one idealized individual organism of a species. As they are assembled from the sequencing of DNA from a number of individual donors, reference genomes do not accurately represent the set of genes of any single individual organism. Instead, a reference provides a haploid mosaic of different DNA sequences from each donor. For example, one of the most recent human reference genomes, assembly GRCh38/hg38 , is derived from >60 genomic clone libraries. [1] There are reference genomes for multiple species of viruses, bacteria, fungus, plants, and animals. Reference genomes are typically used as a guide on which new genomes are built, enabling them to be assembled much more quickly and cheaply than the initial Human Genome Project. Reference genomes can be accessed online at several locations, using dedicated browsers such as Ensembl or UCSC Genome Browser. [2]

Contents

Properties of reference genomes

Measures of length

The length of a genome can be measured in multiple different ways.

A simple way to measure genome length is to count the number of base pairs in the assembly. [3]

The golden path is an alternative measure of length that omits redundant regions such as haplotypes and pseudo autosomal regions. [4] [5] It is usually constructed by layering sequencing information over a physical map to combine scaffold information. It is a 'best estimate' of what the genome will look like and typically includes gaps, making it longer than the typical base pair assembly. [6]

Contigs and scaffolds

Diagram of reads arrangement, forming contigs and these can be assembled into scaffolds in the complete process of sequencing and assembly of a reference genome. The gap between contig 1 and 2 is indicated as sequenced, forming a scaffold, while the other gap is not sequenced and separates scaffold 1 and 2. Contigs and Scaffolds.png
Diagram of reads arrangement, forming contigs and these can be assembled into scaffolds in the complete process of sequencing and assembly of a reference genome. The gap between contig 1 and 2 is indicated as sequenced, forming a scaffold, while the other gap is not sequenced and separates scaffold 1 and 2.

Reference genomes assembly requires reads overlapping, creating contigs, which are contiguous DNA regions of consensus sequences. [7] If there are gaps between contigs, these can be filled by scaffolding, either by contigs amplification with PCR and sequencing or by Bacterial Artificial Chromosome (BAC) cloning. [8] [7] Filling these gaps is not always possible, in this case multiple scaffolds are created in a reference assembly. [9] Scaffolds are classified in 3 types: 1) Placed, whose chromosome, genomic coordinates and orientations are known; 2) Unlocalised, when only the chromosome is known but not the coordinates or orientation; 3) Unplaced, whose chromosome is not known. [10]

The number of contigs and scaffolds, as well as their average lengths are relevant parameters, among many others, for a reference genome assembly quality assessment since they provide information about the continuity of the final mapping from the original genome. The smaller the number of scaffolds per chromosome, until a single scaffold occupies an entire chromosome, the greater the continuity of the genome assembly. [11] [12] [13] Other related parameters are N50 and L50. N50 is the length of the contigs/scaffolds in which the 50% of the assembly is found in fragments of this length or greater, while L50 is the number of contigs/scaffolds whose length is N50. The higher the value of N50, the lower the value of L50, and vice versa, indicating high continuity in the assembly. [14] [15] [16]

Mammalian genomes

The human and mouse reference genomes are maintained and improved by the Genome Reference Consortium (GRC), a group of fewer than 20 scientists from a number of genome research institutes, including the European Bioinformatics Institute, the National Center for Biotechnology Information, the Sanger Institute and McDonnell Genome Institute at Washington University in St. Louis. GRC continues to improve reference genomes by building new alignments that contain fewer gaps, and fixing misrepresentations in the sequence.

Human reference genome

The original human reference genome was derived from thirteen anonymous volunteers from Buffalo, New York. Donors were recruited by advertisement in The Buffalo News , on Sunday, March 23, 1997. The first ten male and ten female volunteers were invited to make an appointment with the project's genetic counselors and donate blood from which DNA was extracted. As a result of how the DNA samples were processed, about 80 percent of the reference genome came from eight people and one male, designated RP11, accounts for 66 percent of the total. The ABO blood group system differs among humans, but the human reference genome contains only an O allele, although the others are annotated. [17] [18] [19] [20] [21]

Evolution of the cost of sequencing a human genome from 2001 to 2021 Cost per Genome.png
Evolution of the cost of sequencing a human genome from 2001 to 2021

As the cost of DNA sequencing falls, and new full genome sequencing technologies emerge, more genome sequences continue to be generated. In several cases people such as James D. Watson had their genome assembled using massive parallel DNA sequencing. [22] [23] Comparison between the reference (assembly NCBI36/hg18) and Watson's genome revealed 3.3  million single nucleotide polymorphism differences, while about 1.4 percent of his DNA could not be matched to the reference genome at all. [21] [22] For regions where there is known to be large-scale variation, sets of alternate loci are assembled alongside the reference locus.

Chromosomes ideogram of the human reference genome assembly GRCh38/hg38. Characteristic bands patterns are displayed in black, grey and white, while the gaps and partially assembled regions are displayed in blue and rose, respectively. Reference: Genome Data Viewer of the NCBI. Human genome assembly GRCh38 chromosomes ideogram NCBI.png
Chromosomes ideogram of the human reference genome assembly GRCh38/hg38. Characteristic bands patterns are displayed in black, grey and white, while the gaps and partially assembled regions are displayed in blue and rose, respectively. Reference: Genome Data Viewer of the NCBI.

The latest human reference genome assembly, released by the Genome Reference Consortium, was GRCh38 in 2017. [25] Several patches were added to update it, the latest patch being GRCh38.p14, published on the 3rd of February 2022. [26] [27] This build only has 349 gaps across the entire assembly, which implies a great improvement in comparison with the first version, which had roughly 150,000 gaps. [18] The gaps are mostly in areas such as telomeres, centromeres, and long repetitive sequences, with the biggest gap along the long arm of the Y chromosome, a region of ~30 Mb in length (~52% of the Y chromosome's length). [28] The number of genomic clone libraries contributing to the reference has increased steadily to >60 over the years, although individual RP11 still accounts for 70% of the reference genome. [1] Genomic analysis of this anonymous male suggests that he is of African-European ancestry. [1] According to the GRC website, their next assembly release for the human genome (version GRCh39) is currently "indefinitely postponed". [29]

In 2022, the Telomere-to-Telomere (T2T) Consortium, [30] an open, community-based effort, published the first completely assembled reference genome (version T2T-CHM13), without any gaps in the assembly. It did not contain a Y-chromosome until version 2.0. [31] [32] This assembly allows for the examination of centromeric and pericentromeric sequence evolution. The consortium employed rigorous methods to assemble, clean, and validate complex repeat regions which are particularly difficult to sequence. [33] It used ultra-long–read (>100 kb) sequencing to accurately sequence segmental duplications. [34]

The T2T-CHM13 is sequenced from CHM13hTERT, a cell line from an essentially haploid hydatidiform mole. "CHM" stands for "Complete Hydatidiform Mole," and "13" is its line number. "hTERT" stands for "human Telomerase Reverse Transcriptase". The cell line has been transfected with the TERT gene, which is responsible for maintaining telomere length and thus contributes to the cell line's immortality. [35] A hydatidiform mole contains two copies of the same parental genome, and thus is essentially haploid. This eliminates allelic variation and allows better sequencing accuracy. [34]

Recent genome assemblies are as follows: [36]

Release nameDate of releaseEquivalent UCSC version
GRCh39Indefinitely postponed [29] -
T2T-CHM13January 2022hs1
GRCh38Dec 2013hg38
GRCh37Feb 2009hg19
NCBI Build 36.1Mar 2006hg18
NCBI Build 35May 2004hg17
NCBI Build 34Jul 2003hg16

Limitations

For much of a genome, the reference provides a good approximation of the DNA of any single individual. But in regions with high allelic diversity, such as the major histocompatibility complex in humans and the major urinary proteins of mice, the reference genome may differ significantly from other individuals. [37] [38] [39] Due to the fact that the reference genome is a "single" distinct sequence, which gives its utility as an index or locator of genomic features, there are limitations in terms of how faithfully it represents the human genome and its variability. Most of the initial samples used for reference genome sequencing came from people of European ancestry. In 2010, it was found that, by de novo assembling genomes from African and Asian populations with the NCBI reference genome (version NCBI36), these genomes had ~5Mb sequences that did not align against any region of the reference genome. [40]

Following projects to the Human Genome Project seek to address a deeper and more diverse characerization of the human genetic variability, which the reference genome is not able to represent. The HapMap Project, active during the period 2002 -2010, with the purpose of creating a haplotypes map and their most common variations among different human populations. Up to 11 populations of different ancestry were studied, such as individuals of the Han ethnic group from China, Gujaratis from India, the Yoruba people from Nigeria or Japanese people, among others. [41] [42] [43] [44] The 1000 Genomes Project, carried out between 2008 and 2015, with the aim of creating a database that includes more than 95% of the variations present in the human genome and whose results can be used in studies of association with diseases (GWAS) such as diabetes, cardiovascular or autoimmune diseases. A total of 26 ethnic groups were studied in this project, expanding the scope of the HapMap project to new ethnic groups such as the Mende people of Sierra Leone, the Vietnamese people or the Bengali people. [45] [46] [47] [48] The Human Pangenome Project, which started its initial phase in 2019 with the creation of the Human Pangenome Reference Consortium, seeks to create the largest map of human genetic variability taking the results of previous studies as a starting point. [49] [50]

Mouse reference genome

Recent mouse genome assemblies are as follows: [36]

Release nameDate of releaseEquivalent UCSC version
GRCm39June 2020mm39
GRCm38Dec 2011mm10
NCBI Build 37Jul 2007mm9
NCBI Build 36Feb 2006mm8
NCBI Build 35Aug 2005mm7
NCBI Build 34Mar 2005mm6

Other genomes

Since the Human Genome Project was finished, multiple international projects have started, focused on assembling reference genomes for many organisms. Model organisms (e.g., zebrafish ( Danio rerio ), chicken ( Gallus gallus ), Escherichia coli etc.) are of special interest to the scientific community, as well as, for example, endangered species (e.g., Asian arowana ( Scleropages formosus) or the American bison ( Bison bison )). As of August 2022, the NCBI database supports 71 886 partially or completely sequenced and assembled genomes from different species, such as 676 mammals, 590 birds and 865 fishes. Also noteworthy are the numbers of 1796 insects genomes, 3747 fungi, 1025 plants, 33 724 bacteria, 26 004 virus and 2040 archaea. [51] A lot of these species have annotation data associated with their reference genomes that can be publicly accessed and visualized in genome browsers such as Ensembl and UCSC Genome Browser. [52] [53]

Some examples of these international projects are: the Chimpanzee Genome Project, carried out between 2005 and 2013 jointly by the Broad Institute and the McDonnell Genome Institute of Washington University in St. Louis, which generated the first reference genomes for 4 subspecies of Pan troglodytes ; [54] [55] the 100K Pathogen Genome Project, which started in 2012 with the main goal of creating a database of reference genomes for 100 000 pathogen microorganisms to use in public health, outbreaks detection, agriculture and environment; [56] the Earth BioGenome Project, which started in 2018 and aims to sequence and catalog the genomes of all the eukaryotic organisms on Earth to promote biodiversity conservation projects. Inside this big-science project there are up to 50 smaller-scale affiliated projects such as the Africa BioGenome Project or the 1000 Fungal Genomes Project. [57] [58] [59]

Related Research Articles

<span class="mw-page-title-main">Genome</span> All genetic material of an organism

In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

In genetics, shotgun sequencing is a method used for sequencing random DNA strands. It is named by analogy with the rapidly expanding, quasi-random shot grouping of a shotgun.

<span class="mw-page-title-main">Human genome</span> Complete set of nucleic acid sequences for humans

The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA sequences and various types of DNA that does not encode proteins. The latter is a diverse category that includes DNA coding for non-translated RNA, such as that for ribosomal RNA, transfer RNA, ribozymes, small nuclear RNAs, and several types of regulatory RNAs. It also includes promoters and their associated gene-regulatory elements, DNA playing structural and replicatory roles, such as scaffolding regions, telomeres, centromeres, and origins of replication, plus large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly repetitive sequences. Introns make up a large percentage of non-coding DNA. Some of this non-coding DNA is non-functional junk DNA, such as pseudogenes, but there is no firm consensus on the total amount of junk DNA.

<span class="mw-page-title-main">Genomics</span> Discipline in genetics

Genomics is an interdisciplinary field of molecular biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dimensional structural configuration. In contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of all of an organism's genes, their interrelations and influence on the organism. Genes may direct the production of proteins with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics also involves the sequencing and analysis of genomes through uses of high throughput DNA sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain.

<span class="mw-page-title-main">Genome project</span> Scientific endeavours to determine the complete genome sequence of an organism

Genome projects are scientific endeavours that ultimately aim to determine the complete genome sequence of an organism and to annotate protein-coding genes and other important genome-encoded features. The genome sequence of an organism includes the collective DNA sequences of each chromosome in the organism. For a bacterium containing a single chromosome, a genome project will aim to map the sequence of that chromosome. For the human species, whose genome includes 22 pairs of autosomes and 2 sex chromosomes, a complete genome sequence will involve 46 separate chromosome sequences.

A contig is a set of overlapping DNA segments that together represent a consensus region of DNA. In bottom-up sequencing projects, a contig refers to overlapping sequence data (reads); in top-down sequencing projects, contig refers to the overlapping clones that form a physical map of the genome that is used to guide sequencing and assembly. Contigs can thus refer both to overlapping DNA sequences and to overlapping physical segments (fragments) contained in clones depending on the context.

In genetics, an expressed sequence tag (EST) is a short sub-sequence of a cDNA sequence. ESTs may be used to identify gene transcripts, and were instrumental in gene discovery and in gene-sequence determination. The identification of ESTs has proceeded rapidly, with approximately 74.2 million ESTs now available in public databases. EST approaches have largely been superseded by whole genome and transcriptome sequencing and metagenome sequencing.

In bioinformatics, sequence assembly refers to aligning and merging fragments from a longer DNA sequence in order to reconstruct the original sequence. This is needed as DNA sequencing technology might not be able to 'read' whole genomes in one go, but rather reads small pieces of between 20 and 30,000 bases, depending on the technology used. Typically, the short fragments (reads) result from shotgun sequencing genomic DNA, or gene transcript (ESTs).

<span class="mw-page-title-main">Metagenomics</span> Study of genes found in the environment

Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microbiomics.

<span class="mw-page-title-main">Epigenome</span> Biological term

In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgenerational epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome. The human epigenome, including DNA methylation and histone modification, is maintained through cell division. The epigenome is essential for normal development and cellular differentiation, enabling cells with the same genetic code to perform different functions. The human epigenome is dynamic and can be influenced by environmental factors such as diet, stress, and toxins.

<span class="mw-page-title-main">Human Genome Project</span> International scientific research project

The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a physical and a functional standpoint. It started in 1990 and was completed in 2003. It remains the world's largest collaborative biological project. Planning for the project started after it was adopted in 1984 by the US government, and it officially launched in 1990. It was declared complete on April 14, 2003, and included about 92% of the genome. Level "complete genome" was achieved in May 2021, with only 0.3% of the bases covered by potential issues. The final gapless assembly was finished in January 2022.

<span class="mw-page-title-main">BBS5</span> Protein-coding gene in the species Homo sapiens

Bardet–Biedl syndrome 5 protein is a protein that in humans is encoded by the BBS5 gene.

<span class="mw-page-title-main">DRC3</span> Protein-coding gene in the species Homo sapiens

Dynein regulatory complex subunit 3 is a protein that in humans is encoded by the DRC3 gene.

<span class="mw-page-title-main">STK40</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase 40 is an enzyme that in humans is encoded by the STK40 gene.

<span class="mw-page-title-main">Scaffolding (bioinformatics)</span> Bioinformatics technique

Scaffolding is a technique used in bioinformatics. It is defined as follows:

Link together a non-contiguous series of genomic sequences into a scaffold, consisting of sequences separated by gaps of known length. The sequences that are linked are typically contiguous sequences corresponding to read overlaps.

Single-cell DNA template strand sequencing, or Strand-seq, is a technique for the selective sequencing of a daughter cell's parental template strands. This technique offers a wide variety of applications, including the identification of sister chromatid exchanges in the parental cell prior to segregation, the assessment of non-random segregation of sister chromatids, the identification of misoriented contigs in genome assemblies, de novo genome assembly of both haplotypes in diploid organisms including humans, whole-chromosome haplotyping, and the identification of germline and somatic genomic structural variation, the latter of which can be detected robustly even in single cells.

Donna R. Maglott is a staff scientist at the National Center for Biotechnology Information known for her research on large-scale genomics projects, including the mouse genome and development of databases required for genomics research.

A plant genome assembly represents the complete genomic sequence of a plant species, which is assembled into chromosomes and other organelles by using DNA fragments that are obtained from different types of sequencing technology.

<span class="mw-page-title-main">Karen Miga</span> American genomics expert

Karen Elizabeth Hayden Miga is an American geneticist who co-leads the Telomere-to-Telomore (T2T) consortium that released fully complete assembly of the human genome in March 2022. She is an assistant professor of biomolecular engineering at the University of California, Santa Cruz and Associate Director of Human Pangenomics at the UC Santa Cruz Genomics Institute. She was named as "One to Watch" in the 2020 Nature's 10 and one of Time 100’s most influential people of 2022.

References

  1. 1 2 3 "How many individuals were sequenced for the human reference genome assembly?". Genome Reference Consortium. Retrieved 7 April 2022.
  2. ↑ Flicek P, Aken BL, Beal K, Ballester B, Caccamo M, Chen Y, et al. (January 2008). "Ensembl 2008". Nucleic Acids Research. 36 (Database issue): D707–D714. doi:10.1093/nar/gkm988. PMC   2238821 . PMID   18000006.
  3. ↑ "Help - Glossary - Homo sapiens - Ensembl genome browser 87". www.ensembl.org.
  4. ↑ "Golden path length | VectorBase". www.vectorbase.org. Archived from the original on 2020-08-07. Retrieved 2016-12-12.
  5. ↑ "Help - Glossary - Homo sapiens - Ensembl genome browser 87". www.ensembl.org.
  6. ↑ "Whole assembly vs Golden path length in Ensembl? - SEQanswers". seqanswers.com. 31 July 2014. Retrieved 2016-12-12.
  7. 1 2 Gibson, Greg; Muse, Spencer V. (2009). A Primer of Genome Science (3rd ed.). Sinauer Associates. p. 84. ISBN   978-0-878-93236-8.
  8. ↑ "Help - Glossary - Homo_sapiens - Ensembl genome browser 107". www.ensembl.org. Retrieved 2022-09-26.
  9. ↑ Luo, Junwei; Wei, Yawei; Lyu, Mengna; Wu, Zhengjiang; Liu, Xiaoyan; Luo, Huimin; Yan, Chaokun (2021-09-02). "A comprehensive review of scaffolding methods in genome assembly". Briefings in Bioinformatics. 22 (5): bbab033. doi:10.1093/bib/bbab033. ISSN   1477-4054. PMID   33634311.
  10. ↑ "Chromosomes, scaffolds and contigs". www.ensembl.org. Retrieved 2022-09-26.
  11. ↑ Meader, Stephen; Hillier, LaDeana W.; Locke, Devin; Ponting, Chris P.; Lunter, Gerton (May 2010). "Genome assembly quality: Assessment and improvement using the neutral indel model". Genome Research. 20 (5): 675–684. doi:10.1101/gr.096966.109. ISSN   1088-9051. PMC   2860169 . PMID   20305016.
  12. ↑ Rice, Edward S.; Green, Richard E. (2019-02-15). "New Approaches for Genome Assembly and Scaffolding". Annual Review of Animal Biosciences. 7 (1): 17–40. doi:10.1146/annurev-animal-020518-115344. ISSN   2165-8102. PMID   30485757. S2CID   54121772.
  13. ↑ Cao, Minh Duc; Nguyen, Son Hoang; Ganesamoorthy, Devika; Elliott, Alysha G.; Cooper, Matthew A.; Coin, Lachlan J. M. (2017-02-20). "Scaffolding and completing genome assemblies in real-time with nanopore sequencing". Nature Communications. 8 (1): 14515. Bibcode:2017NatCo...814515C. doi: 10.1038/ncomms14515 . ISSN   2041-1723. PMC   5321748 . PMID   28218240.
  14. ↑ Mende, Daniel R.; Waller, Alison S.; Sunagawa, Shinichi; Järvelin, Aino I.; Chan, Michelle M.; Arumugam, Manimozhiyan; Raes, Jeroen; Bork, Peer (2012-02-23). "Assessment of Metagenomic Assembly Using Simulated Next Generation Sequencing Data". PLOS ONE. 7 (2): e31386. Bibcode:2012PLoSO...731386M. doi: 10.1371/journal.pone.0031386 . ISSN   1932-6203. PMC   3285633 . PMID   22384016.
  15. ↑ Alhakami, Hind; Mirebrahim, Hamid; Lonardi, Stefano (2017-05-18). "A comparative evaluation of genome assembly reconciliation tools". Genome Biology. 18 (1): 93. doi: 10.1186/s13059-017-1213-3 . ISSN   1474-7596. PMC   5436433 . PMID   28521789.
  16. ↑ Castro, Christina J.; Ng, Terry Fei Fan (2017-11-01). "U50: A New Metric for Measuring Assembly Output Based on Non-Overlapping, Target-Specific Contigs". Journal of Computational Biology. 24 (11): 1071–1080. doi:10.1089/cmb.2017.0013. PMC   5783553 . PMID   28418726.
  17. ↑ Scherer S (2008). A short guide to the human genome. CSHL Press. p. 135. ISBN   978-0-87969-791-4.
  18. 1 2 "E pluribus unum". Nature Methods. 7 (5): 331. May 2010. doi: 10.1038/nmeth0510-331 . PMID   20440876.
  19. ↑ Ballouz S, Dobin A, Gillis JA (August 2019). "Is it time to change the reference genome?". Genome Biology. 20 (1): 159. doi: 10.1186/s13059-019-1774-4 . PMC   6688217 . PMID   31399121.
  20. ↑ Rosenfeld JA, Mason CE, Smith TM (11 July 2012). "Limitations of the human reference genome for personalized genomics". PLOS ONE. 7 (7): e40294. Bibcode:2012PLoSO...740294R. doi: 10.1371/journal.pone.0040294 . PMC   3394790 . PMID   22811759.
  21. 1 2 Wade N (May 31, 2007). "Genome of DNA Pioneer Is Deciphered". New York Times. Retrieved February 21, 2009.
  22. 1 2 Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, et al. (April 2008). "The complete genome of an individual by massively parallel DNA sequencing". Nature. 452 (7189): 872–876. Bibcode:2008Natur.452..872W. doi: 10.1038/nature06884 . PMID   18421352.
  23. ↑ The exception to this is J. Craig Venter whose DNA was sequenced and assembled using shotgun sequencing methods.
  24. ↑ "Genome Data Viewer - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-08-18.
  25. ↑ Schneider VA, Graves-Lindsay T, Howe K, Bouk N, Chen HC, Kitts PA, et al. (May 2017). "Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly". Genome Research. 27 (5): 849–864. doi:10.1101/gr.213611.116. PMC   5411779 . PMID   28396521.
  26. ↑ "GRCh38.p14 - hg38 - Genome - Assembly - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-08-19.
  27. ↑ Genome Reference Consortium (2022-05-09). "GenomeRef: GRCh38.p14 is now released!". GRC Blog (GenomeRef). Retrieved 2022-08-19.
  28. ↑ "GRCh38.p14 - hg38 - Genome - Assembly - NCBI - Statistics Report". www.ncbi.nlm.nih.gov. Retrieved 2022-08-18.
  29. 1 2 "Genome Reference Consortium". www.ncbi.nlm.nih.gov. Retrieved 2022-08-18.
  30. ↑ "Telomere-to-Telomere". NHGRI. Retrieved 2022-08-16.
  31. ↑ Nurk S, Koren S, Rhie A, Rautiainen M, Bzikadze AV, Mikheenko A, et al. (April 2022). "The complete sequence of a human genome". Science. 376 (6588): 44–53. Bibcode:2022Sci...376...44N. doi:10.1126/science.abj6987. PMC   9186530 . PMID   35357919. S2CID   247854936.
  32. ↑ "T2T-CHM13v2.0 - Genome - Assembly - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-08-16.
  33. ↑ Altemose, Nicolas; Logsdon, Glennis A.; Bzikadze, Andrey V.; Sidhwani, Pragya; Langley, Sasha A.; Caldas, Gina V.; Hoyt, Savannah J.; Uralsky, Lev; Ryabov, Fedor D.; Shew, Colin J.; Sauria, Michael E. G.; Borchers, Matthew; Gershman, Ariel; Mikheenko, Alla; Shepelev, Valery A. (April 2022). "Complete genomic and epigenetic maps of human centromeres". Science. 376 (6588): eabl4178. doi:10.1126/science.abl4178. ISSN   0036-8075. PMC   9233505 . PMID   35357911.
  34. 1 2 Church, Deanna M. (April 2022). "A next-generation human genome sequence". Science. 376 (6588): 34–35. Bibcode:2022Sci...376...34C. doi:10.1126/science.abo5367. ISSN   0036-8075. PMID   35357937.
  35. ↑ Steinberg, Karyn Meltz; Schneider, Valerie A.; Graves-Lindsay, Tina A.; Fulton, Robert S.; Agarwala, Richa; Huddleston, John; Shiryev, Sergey A.; Morgulis, Aleksandr; Surti, Urvashi; Warren, Wesley C.; Church, Deanna M.; Eichler, Evan E.; Wilson, Richard K. (December 2014). "Single haplotype assembly of the human genome from a hydatidiform mole". Genome Research. 24 (12): 2066–2076. doi:10.1101/gr.180893.114. ISSN   1088-9051. PMC   4248323 . PMID   25373144.
  36. 1 2 "UCSC Genome Bioinformatics: FAQ". genome.ucsc.edu. Retrieved 2016-08-18.
  37. ↑ MHC Sequencing Consortium (October 1999). "Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium". Nature. 401 (6756): 921–923. Bibcode:1999Natur.401..921T. doi:10.1038/44853. PMID   10553908. S2CID   186243515.
  38. ↑ Logan DW, Marton TF, Stowers L (September 2008). Vosshall LB (ed.). "Species specificity in major urinary proteins by parallel evolution". PLOS ONE. 3 (9): e3280. Bibcode:2008PLoSO...3.3280L. doi: 10.1371/journal.pone.0003280 . PMC   2533699 . PMID   18815613.
  39. ↑ Hurst J, Beynon RJ, Roberts SC, Wyatt TD (October 2007). Urinary Lipocalins in Rodenta:is there a Generic Model?. Chemical Signals in Vertebrates 11. Springer New York. ISBN   978-0-387-73944-1.
  40. ↑ Li R, Li Y, Zheng H, Luo R, Zhu H, Li Q, et al. (January 2010). "Building the sequence map of the human pan-genome". Nature Biotechnology. 28 (1): 57–63. doi:10.1038/nbt.1596. PMID   19997067. S2CID   205274447.
  41. ↑ The International HapMap Consortium (October 2005). "A haplotype map of the human genome". Nature. 437 (7063): 1299–1320. Bibcode:2005Natur.437.1299T. doi:10.1038/nature04226. PMC   1880871 . PMID   16255080.
  42. ↑ Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, et al. (October 2007). "A second generation human haplotype map of over 3.1 million SNPs". Nature. 449 (7164): 851–861. Bibcode:2007Natur.449..851F. doi:10.1038/nature06258. PMC   2689609 . PMID   17943122.
  43. ↑ Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, et al. (September 2010). "Integrating common and rare genetic variation in diverse human populations". Nature. 467 (7311): 52–58. Bibcode:2010Natur.467...52T. doi:10.1038/nature09298. PMC   3173859 . PMID   20811451.
  44. ↑ "International HapMap Project". Genome.gov. Retrieved 2022-08-18.
  45. ↑ Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, et al. (October 2010). "A map of human genome variation from population-scale sequencing". Nature. 467 (7319): 1061–1073. Bibcode:2010Natur.467.1061T. doi:10.1038/nature09534. PMC   3042601 . PMID   20981092.
  46. ↑ Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. (November 2012). "An integrated map of genetic variation from 1,092 human genomes". Nature. 491 (7422): 56–65. Bibcode:2012Natur.491...56T. doi:10.1038/nature11632. PMC   3498066 . PMID   23128226.
  47. ↑ Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. (October 2015). "A global reference for human genetic variation". Nature. 526 (7571): 68–74. Bibcode:2015Natur.526...68T. doi:10.1038/nature15393. PMC   4750478 . PMID   26432245.
  48. ↑ Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. (October 2015). "An integrated map of structural variation in 2,504 human genomes". Nature. 526 (7571): 75–81. Bibcode:2015Natur.526...75.. doi:10.1038/nature15394. PMC   4617611 . PMID   26432246.
  49. ↑ Miga KH, Wang T (August 2021). "The Need for a Human Pangenome Reference Sequence". Annual Review of Genomics and Human Genetics. 22 (1): 81–102. doi:10.1146/annurev-genom-120120-081921. PMC   8410644 . PMID   33929893.
  50. ↑ Wang T, Antonacci-Fulton L, Howe K, Lawson HA, Lucas JK, Phillippy AM, et al. (April 2022). "The Human Pangenome Project: a global resource to map genomic diversity". Nature. 604 (7906): 437–446. Bibcode:2022Natur.604..437W. doi:10.1038/s41586-022-04601-8. PMC   9402379 . PMID   35444317. S2CID   248297723.
  51. ↑ "Genome List - Genome - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-08-18.
  52. ↑ "Species List". uswest.ensembl.org. Archived from the original on 2022-08-06. Retrieved 2022-08-18.
  53. ↑ "GenArk: UCSC Genome Archive". hgdownload.soe.ucsc.edu. Retrieved 2022-08-18.
  54. ↑ "Chimpanzee Genome Project". BCM-HGSC. 2016-03-04. Retrieved 2022-08-18.
  55. ↑ Prado-Martinez J, Sudmant PH, Kidd JM, Li H, Kelley JL, Lorente-Galdos B, et al. (July 2013). "Great ape genetic diversity and population history". Nature. 499 (7459): 471–475. Bibcode:2013Natur.499..471P. doi:10.1038/nature12228. PMC   3822165 . PMID   23823723.
  56. ↑ "100K Pathogen Genome Project – Genomes for Public Health & Food Safety" . Retrieved 2022-08-18.
  57. ↑ Lewin HA, Robinson GE, Kress WJ, Baker WJ, Coddington J, Crandall KA, et al. (April 2018). "Earth BioGenome Project: Sequencing life for the future of life". Proceedings of the National Academy of Sciences of the United States of America. 115 (17): 4325–4333. Bibcode:2018PNAS..115.4325L. doi: 10.1073/pnas.1720115115 . PMC   5924910 . PMID   29686065.
  58. ↑ "African BioGenome Project – Genomics in the service of conservation and improvement of African biological diversity" . Retrieved 2022-08-18.
  59. ↑ "1000 Fungal Genomes Project". mycocosm.jgi.doe.gov. Retrieved 2022-08-18.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.