Reference genome

, London A reference genome is a genome assembly that represents the complete genetic sequence of an organism as a continuous string of nucleotides (A, T, C, and G). For an assembly to serve as a reference genome, it is typically accompanied by annotations, produced through a process known as DNA or genome annotation. The annotations specify the genomic coordinates (start and end locations) of genes, exons, introns, and mRNA, and are often paired with corresponding transcript (mRNA) and protein sequences (algorithm predicted or experimentally validated). Reference genomes exist for a wide variety of species, including species of viruses, bacteria, fungi, plants and animals, and they differ in how they are constructed and represented. A reference may be derived from a single individual or from multiple individuals whose sequences are collapsed into one representative assembly - haplotype. Two main factors determine reference genome's assembly quality: the sequencing technology which affects sequence accuracy and the assembly level which indicates how complete the genome representation is. The ideal is a chromosome-level assembly, which is a complete DNA sequence for each chromosome with no unplaced segments. However, achieving this remains technically challenging, especially for large or repetitive genomes (dense in repetitive elements).…

, London]] A reference genome is a genome assembly that represents the complete genetic sequence of an organism as a continuous string of nucleotides (A, T, C, and G). For an assembly to serve as a reference genome, it is typically accompanied by annotations, produced through a process known as DNA or genome annotation. The annotations specify the genomic coordinates (start and end locations) of genes, exons, introns, and mRNA, and are often paired with corresponding transcript (mRNA) and protein sequences (algorithm predicted or experimentally validated). Reference genomes exist for a wide variety of species, including species of viruses, bacteria, fungi, plants and animals, and they differ in how they are constructed and represented. A reference may be derived from a single individual or from multiple individuals whose sequences are collapsed into one representative assembly - haplotype. Two main factors determine reference genome's assembly quality: the sequencing technology which affects sequence accuracy and the assembly level which indicates how complete the genome representation is. The ideal is a chromosome-level assembly, which is a complete DNA sequence for each chromosome with no unplaced segments. However, achieving this remains technically challenging, especially for large or repetitive genomes (dense in repetitive elements). Earlier sequencing technologies often produced assemblies at the contig (short contiguous sequences) or scaffold (ordered sets of contigs) level, with limited chromosomal context. The exact size of these fragments depends on the sequencing platform and bioinformatic methods available at the time. For assemblies that are not fully resolved, summary statistics such as N50 and L50 are commonly used to characterise contiguity and assembly fragmentation; these metrics are explained in the Contigs and Scaffolds section. Reference genomes are central to omics research, particularly genomics. They provide a reference for "mapping" DNA sequence data from many individuals, enabling efficient identification of the genomic location of these sequences and the detection of polymorphisms (sequence differences among individuals) through a process known as variant calling. The limitations of this practice, such as reference bias and under-representation of population diversity, have led to the development of population-level reference sets and pangenomes. Reference genomes and their annotations are publicly accessible through online genome browsers and archives such as Ensembl, the European Nucleotide Archive (ENA) at EMBL-EBI, the UCSC Genome Browser, and NCBI. ==Properties of reference genomes== ==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; one male, designated RP11, accounts for 66 percent of the total genome. The ABO blood group system differs among humans, but the human reference genome contains only an O allele, although the others are annotated. ]] 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. 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. For regions where there is known to be large-scale variation, sets of alternate loci are assembled alongside the reference locus. The latest human reference genome assembly, released by the Genome Reference Consortium, was GRCh38 in 2017¹. Several patches were added to update it, the latest patch being GRCh38.p14, published on the 3rd of February 2022¹. 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. 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). 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. Genomic analysis of this anonymous male suggests that he is of African-European ancestry. According to the GRC website, their next assembly release for the human genome (version GRCh39) is currently "indefinitely postponed". In 2022, the Telomere-to-Telomere (T2T) Consortium, 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. 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. It used ultra-long–read (>100 kb) sequencing to accurately sequence segmental duplications. 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. 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. Recent genome assemblies are as follows: ==See also== European Reference Genome Atlas

Text derived from https://en.wikipedia.org/w/index.php?oldid=1353765350 under CC BY-SA 4.0; modifications have been made.