The human genome is a complete set of nucleic acid sequences for humans, encoded as the DNA within each of the 24 distinct chromosomes in the cell nucleus. A small DNA molecule is 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.
Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.
The International HapMap Project was an organization that aimed to develop a haplotype map (HapMap) of the human genome, to describe the common patterns of human genetic variation. HapMap is used to find genetic variants affecting health, disease and responses to drugs and environmental factors. The information produced by the project is made freely available for research.
Comparative genomics is a branch of biological research that examines genome sequences across a spectrum of species, spanning from humans and mice to a diverse array of organisms from bacteria to chimpanzees. This large-scale holistic approach compares two or more genomes to discover the similarities and differences between the genomes and to study the biology of the individual genomes. Comparison of whole genome sequences provides a highly detailed view of how organisms are related to each other at the gene level. By comparing whole genome sequences, researchers gain insights into genetic relationships between organisms and study evolutionary changes. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. Therefore, Comparative genomics provides a powerful tool for studying evolutionary changes among organisms, helping to identify genes that are conserved or common among species, as well as genes that give unique characteristics of each organism. Moreover, these studies can be performed at different levels of the genomes to obtain multiple perspectives about the organisms.
Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype.
Human genetic variation is the genetic differences in and among populations. There may be multiple variants of any given gene in the human population (alleles), a situation called polymorphism.
The Neanderthal genome project is an effort, founded in July 2006, of a group of scientists to sequence the Neanderthal genome.
The 1000 Genomes Project (1KGP), taken place from January 2008 to 2015, was an international research effort to establish the most detailed catalogue of human genetic variation at the time. Scientists planned to sequence the genomes of at least one thousand anonymous healthy participants from a number of different ethnic groups within the following three years, using advancements in newly developed technologies. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal Nature. In 2012, the sequencing of 1092 genomes was announced in a Nature publication. In 2015, two papers in Nature reported results and the completion of the project and opportunities for future research.
The Centre for Applied Genomics is a genome centre in the Research Institute of The Hospital for Sick Children, and is affiliated with the University of Toronto. TCAG also operates as a Science and Technology Innovation Centre of Genome Canada, with an emphasis on next-generation sequencing (NGS) and bioinformatics support. Research at TCAG focuses on the genetic and genomic basis of human variability, health and disease, including research on the genetics of autism spectrum disorder and structural variation of the human genome. The centre is located in the Peter Gilgan Centre for Research and Learning in downtown Toronto, Canada.
DECIPHER is a web-based resource and database of genomic variation data from analysis of patient DNA. It documents submicroscopic chromosome abnormalities and pathogenic sequence variants, from over 25000 patients and maps them to the human genome using Ensembl or UCSC Genome Browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndromes, together with links to relevant scientific reports and support groups.
The Center for Applied Genomics is a research center at the Children's Hospital of Philadelphia that focuses on genomics research and the utilization of basic research findings in the development of new medical treatments.
Stephen Wayne "Steve" Scherer is a Canadian scientist who currently serves as the Chief of Research at The Hospital for Sick Children (SickKids) and distinguished University Professor at the University of Toronto. He obtained his PhD at the University of Toronto under Professor Lap-chee Tsui. Together they founded the Centre for Applied Genomics (TCAG). He is a Senior Fellow of Massey College at the University of Toronto. In 2014, he was named an esteemed Clarivate Citation laureate in Physiology or Medicine for the “Discovery of large-scale gene copy number variation and its association with specific diseases.”
Genomic structural variation is the variation in structure of an organism's chromosome, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Originally, a structure variation affects a sequence length about 1kb to 3Mb, which is larger than SNPs and smaller than chromosome abnormality. However, the operational range of structural variants has widened to include events > 50bp. Some structural variants are associated with genetic diseases, however most are not. Approximately 13% of the human genome is defined as structurally variant in the normal population, and there are at least 240 genes that exist as homozygous deletion polymorphisms in human populations, suggesting these genes are dispensable in humans. While humans carry a median of 3.6 Mbp in SNPs, a median of 8.9 Mbp is affected by structural variation which thus causes most genetic differences between humans in terms of raw sequence data.
Transmission electron microscopy DNA sequencing is a single-molecule sequencing technology that uses transmission electron microscopy techniques. The method was conceived and developed in the 1960s and 70s, but lost favor when the extent of damage to the sample was recognized.
Single-cell sequencing examines the nucleic acid sequence information from individual cells with optimized next-generation sequencing technologies, providing a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment. For example, in cancer, sequencing the DNA of individual cells can give information about mutations carried by small populations of cells. In development, sequencing the RNAs expressed by individual cells can give insight into the existence and behavior of different cell types. In microbial systems, a population of the same species can appear genetically clonal. Still, single-cell sequencing of RNA or epigenetic modifications can reveal cell-to-cell variability that may help populations rapidly adapt to survive in changing environments.
Structural variation in the human genome is operationally defined as genomic alterations, varying between individuals, that involve DNA segments larger than 1 kilo base (kb), and could be either microscopic or submicroscopic. This definition distinguishes them from smaller variants that are less than 1 kb in size such as short deletions, insertions, and single nucleotide variants.
ANNOVAR is a bioinformatics software tool for the interpretation and prioritization of single nucleotide variants (SNVs), insertions, deletions, and copy number variants (CNVs) of a given genome.
Emmanouil Theophilos Dermitzakis is a Greek human geneticist and despotic professor in the Department of Genetic Medicine and Development at the University of Geneva, where he is also Director of the Health 2030 Genome Center. He is an ISI Highly Cited Researcher and an elected member of the European Molecular Biology Organization. He is a member of the Swiss Institute of Bioinformatics, where his research group is focused on the genetics and genomics of complex traits in humans. He has joined GlaxoSmithKline as Vice President, Computational Biology in R&D.
Matthew Edward Hurles is director of the Wellcome Sanger Institute and an honorary professor of Human Genetics and Genomics at the University of Cambridge.
Circular consensus sequencing (CCS) is a DNA sequencing method that is used in conjunction with single-molecule real-time sequencing to yield highly accurate long-read sequencing datasets with read lengths averaging 15–25 kb with median accuracy greater than 99.9%. These long reads, which are created via the formation of consensus sequencing obtained from multiple passes on a single DNA molecule, can be used to improve results for complex applications such as single nucleotide and structural variant detection, genome assembly, assembly of difficult polyploid or highly repetitive genomes, and assembly of metagenomes.
