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1.
Nature ; 604(7905): 310-315, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35388217

RESUMEN

Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.


Asunto(s)
Biología Computacional , Bases de Datos Genéticas , Genómica , Genoma , Humanos , Difusión de la Información , Anotación de Secuencia Molecular , National Library of Medicine (U.S.) , Estados Unidos
2.
Nucleic Acids Res ; 47(D1): D745-D751, 2019 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-30407521

RESUMEN

The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.


Asunto(s)
Bases de Datos Genéticas , Genoma/genética , Genómica , Vertebrados/genética , Animales , Biología Computacional/tendencias , Humanos , Ratones , Anotación de Secuencia Molecular , Programas Informáticos
3.
Genome Res ; 27(5): 849-864, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28396521

RESUMEN

The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health.


Asunto(s)
Mapeo Contig/métodos , Genoma Humano , Genómica/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Mapeo Contig/normas , Genómica/normas , Haploidia , Haplotipos , Humanos , Polimorfismo Genético , Estándares de Referencia , Análisis de Secuencia de ADN/normas
4.
Genome Res ; 26(1): 130-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26560630

RESUMEN

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.


Asunto(s)
Cromosomas de los Mamíferos/genética , Evolución Molecular , Porcinos/genética , Cromosoma X/genética , Cromosoma Y/genética , Animales , Secuencia de Bases , Gatos/genética , Perros/genética , Femenino , Conversión Génica , Expresión Génica , Biblioteca de Genes , Orden Génico , Humanos , Masculino , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN
6.
Nat Genet ; 50(11): 1574-1583, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30275530

RESUMEN

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.


Asunto(s)
Mapeo Cromosómico , Sitios Genéticos , Genoma , Haplotipos , Ratones Endogámicos/genética , Animales , Animales de Laboratorio , Mapeo Cromosómico/veterinaria , Haplotipos/genética , Ratones , Ratones Endogámicos BALB C/genética , Ratones Endogámicos C3H/genética , Ratones Endogámicos C57BL/genética , Ratones Endogámicos CBA/genética , Ratones Endogámicos DBA/genética , Ratones Endogámicos NOD/genética , Ratones Endogámicos/clasificación , Anotación de Secuencia Molecular , Filogenia , Polimorfismo de Nucleótido Simple , Especificidad de la Especie
7.
Nature ; 418(6899): 743-50, 2002 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-12181558

RESUMEN

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.


Asunto(s)
Genoma , Ratones/genética , Mapeo Físico de Cromosoma/métodos , Animales , Cromosomas/genética , Cromosomas Humanos Par 6/genética , Clonación Molecular , Secuencia Conservada/genética , Mapeo Contig/métodos , Genoma Humano , Humanos , Datos de Secuencia Molecular , Mapeo de Híbrido por Radiación , Alineación de Secuencia , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie , Sintenía
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