The decade since the Human Genome Project ended has witnessed a remarkable sequencing technology explosion that has permitted a multitude of questions about the genome to be asked and answered, at ...unprecedented speed and resolution. Here I present examples of how the resulting information has both enhanced our knowledge and expanded the impact of the genome on biomedical research. New sequencing technologies have also introduced exciting new areas of biological endeavour. The continuing upward trajectory of sequencing technology development is enabling clinical applications that are aimed at improving medical diagnosis and treatment.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing ...platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45-to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.
Comprehensive, high-quality reference genomes are required for functional characterization and taxonomic assignment of the human gut microbiota. We present the Unified Human Gastrointestinal Genome ...(UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. These genomes encode >170 million protein sequences, which we collated in the Unified Human Gastrointestinal Protein (UHGP) catalog. The UHGP more than doubles the number of gut proteins in comparison to those present in the Integrated Gene Catalog. More than 70% of the UHGG species lack cultured representatives, and 40% of the UHGP lack functional annotations. Intraspecies genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which are specific to individual human populations. The UHGG and UHGP collections will enable studies linking genotypes to phenotypes in the human gut microbiome.
Complex allelic variation hampers the assembly of haplotype-resolved sequences from diploid genomes. We developed trio binning, an approach that simplifies haplotype assembly by resolving allelic ...variation before assembly. In contrast with prior approaches, the effectiveness of our method improved with increasing heterozygosity. Trio binning uses short reads from two parental genomes to first partition long reads from an offspring into haplotype-specific sets. Each haplotype is then assembled independently, resulting in a complete diploid reconstruction. We used trio binning to recover both haplotypes of a diploid human genome and identified complex structural variants missed by alternative approaches. We sequenced an F1 cross between the cattle subspecies Bos taurus taurus and Bos taurus indicus and completely assembled both parental haplotypes with NG50 haplotig sizes of >20 Mb and 99.998% accuracy, surpassing the quality of current cattle reference genomes. We suggest that trio binning improves diploid genome assembly and will facilitate new studies of haplotype variation and inheritance.
One of the major questions in human genetics is what percentage of individuals in the general population carry a disease-causing mutation. Based on publicly available information on genotypes from ...six main world populations, we created a database including data on 276,921 sequence variants, present within 187 genes associated with autosomal recessive (AR) inherited retinal diseases (IRDs). Assessment of these variants revealed that 10,044 were categorized as disease-causing mutations. We developed an algorithm to compute the gene-specific prevalence of disease, as well as the mutational burden in healthy subjects. We found that the genetic prevalence of AR-IRDs corresponds approximately to 1 case in 1,380 individuals, with 5.5 million people expected to be affected worldwide. In addition, we calculated that unaffected carriers ofmutations are numerous, ranging from 1 in 2.26 individuals in Europeans to 1 in 3.50 individuals in the Finnish population. Our analysis indicates that about 2.7 billion people worldwide (36% of the population) are healthy carriers of at least one mutation that can cause AR-IRD, a value that is probably the highest across any group of Mendelian conditions in humans.
Pan-genomics in the human genome era Sherman, Rachel M; Salzberg, Steven L
Nature reviews. Genetics,
04/2020, Letnik:
21, Številka:
4
Journal Article
Recenzirano
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Since the early days of the genome era, the scientific community has relied on a single 'reference' genome for each species, which is used as the basis for a wide range of genetic analyses, including ...studies of variation within and across species. As sequencing costs have dropped, thousands of new genomes have been sequenced, and scientists have come to realize that a single reference genome is inadequate for many purposes. By sampling a diverse set of individuals, one can begin to assemble a pan-genome: a collection of all the DNA sequences that occur in a species. Here we review efforts to create pan-genomes for a range of species, from bacteria to humans, and we further consider the computational methods that have been proposed in order to capture, interpret and compare pan-genome data. As scientists continue to survey and catalogue the genomic variation across human populations and begin to assemble a human pan-genome, these efforts will increase our power to connect variation to human diversity, disease and beyond.
Introduction: Epigenetics is the study of the interaction between genotype and phenotype, first described by Waddingtonen in 1939. Objective: To identify new technologies that predict clinical ...markers of perinatal maternal risk with the help of epigenetics. Method: We searched all the databases that have had an impact worldwide, including Elsevier, WoS, Pubmed, Scielo, Redalyc, among others, generating a search with the terms epigenetic, clinical markers. Results: Of a total of 37 preselected articles, three were discarded, selecting 34 articles that met the inclusion/exclusion criteria in all that covers the topic and objective of this research work. Discussion: There are new lines of research that allow to know the epigenome of each individual and how the environment interact on it. Epigenetic biomarkers that exceed the usual diagnostic techniques on different pathologies are being developed. It is very important to continue in the search for information, for this reason several countries that have the appropriate technology are conducting epigenetic studies for later use in medicine. Conclusion: The woman during pregnancy experiences a series of changes that predispose her to the development of some pathology and the research in them is limited by her condition, but the diseases that stand out are diabetes, obesity and preeclampsia where epigenetics has shown that changes in specific genes occur.
Keywords: epigenetic, human genome, biomarkers.
RESUMEN
Introducción: La epigenética es el estudio de la interacción entre el genotipo y el fenotipo, descrito por primera vez por Waddingtonen en 1939. Objetivo: Identificar nuevas tecnologías que pronostiquen marcadores clínicos de riesgo materno perinatal con ayuda de la epigenética. Método: Se procedió a realizar búsquedas en todas las bases de datos que a nivel mundial han tomado impacto, entre ellas están Elsevier, WoS, Pubmed, Scielo, Redalyc, entre otros, generando búsqueda con los términos epigenética, marcadores clínicos. Resultados: De un total de 37 artículos preseleccionados, se descartó tres, seleccionando 34 artículos que cumplían con los criterios de inclusión/exclusión en todo lo que abarca el tema y el objetivo de este trabajo investigativo. Discusión: Existen nuevas líneas de investigación que permiten conocer el epigenoma de cada individuo y como el ambiente influye sobre este. Se están desarrollando biomarcadores epigenéticos que superen las técnicas habituales de diagnóstico para la detección de diversas patologías. Es muy importante seguir en la búsqueda de información, por esto varios países que cuentan con la tecnología adecuada se encuentran realizando estudios de epigenética para su uso posterior en la medicina. Conclusión: La mujer durante el embarazo experimenta una serie de cambios que le predisponen al desarrollo de alguna patología y las investigaciones en ellas se ven limitadas por su condición, pero las enfermedades que resaltan son la diabetes, obesidad y la preeclampsia donde la epigenética ha demostrado que suceden cambios en genes específicos.
Palabras clave: epigenética, genoma humano, biomarcadores
Comprehensively characterizing the cellular composition and organization of tissues has been a long-term scientific challenge that has limited our ability to study fundamental and clinical aspects of ...human physiology. The Human Cell Atlas (HCA) is a global collaborative effort to create a reference map of all human cells as a basis for both understanding human health and diagnosing, monitoring, and treating disease. Many aspects of the HCA are analogous to the Human Genome Project (HGP), whose completion presents a major milestone in modern biology. To commemorate the HGP’s 20-year anniversary of completion, we discuss the launch of the HCA in light of the HGP, and highlight recent progress by the HCA consortium.
The Human Cell Atlas (HCA) consortium was founded as a collaborative and open effort to create a reference map of the cells in the human body.Organizing a large-scale project such as the HCA draws inspiration from the Human Genome Project (HGP) that was completed 20 years ago.Significant progress has been made by the HCA community, including profiling more than 39 million cells from 15 major organs to date.The expected impact of the HCA is illustrated by its use during the coronavirus disease 2019 (COVID-19) pandemic.
Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate genomic analysis in chordate species with an emphasis on human, major vertebrate model organisms and farm animals. Over ...the past year we have increased the number of species that we support to 77 and expanded our genome browser with a new scrollable overview and improved variation and phenotype views. We also report updates to our core datasets and improvements to our gene homology relationships from the addition of new species. Our REST service has been extended with additional support for comparative genomics and ontology information. Finally, we provide updated information about our methods for data access and resources for user training.
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