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.
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.
Comparative genomic hybridization (CGH) is a molecular cytogenetic method for analysing copy number variations (CNVs) relative to ploidy level in the DNA of a test sample compared to a reference sample,without the need for culturing cells. The aim of this technique is to quickly and efficiently compare two genomic DNA samples arising from two sources,which are most often closely related,because it is suspected that they contain differences in terms of either gains or losses of either whole chromosomes or subchromosomal regions. This technique was originally developed for the evaluation of the differences between the chromosomal complements of solid tumor and normal tissue,and has an improved resolution of 5–10 megabases compared to the more traditional cytogenetic analysis techniques of giemsa banding and fluorescence in situ hybridization (FISH) which are limited by the resolution of the microscope utilized.
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.
Deleted in azoospermia protein 3 is a protein that in humans is encoded by the DAZ3 gene.
Testis-specific chromodomain protein Y 1 is a protein that in humans is encoded by the CDY1 gene.
Sodium/myo-inositol cotransporter is a protein that in humans is encoded by the SLC5A3 gene.
Zinc finger protein 33B is a protein that in humans is encoded by the ZNF33B gene.
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.
Koolen–De Vries syndrome (KdVS),also known as 17q21.31 microdeletion syndrome,is a rare genetic disorder caused by a deletion of a segment of chromosome 17 which contains six genes. This deletion syndrome was discovered independently in 2006 by three different research groups.
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.
Non-allelic homologous recombination (NAHR) is a form of homologous recombination that occurs between two lengths of DNA that have high sequence similarity,but are not alleles.
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 Canada's first human genome centre,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.
Condensin-2 complex subunit H2,also known as chromosome-associated protein H2 (CAP-H2) or non-SMC condensin II complex subunit H2 (NCAPH2),is a protein that in humans is encoded by the NCAPH2 gene. CAP-H2 is a subunit of condensin II,a large protein complex involved in chromosome condensation.
The 2000s witnessed an explosion of genome sequencing and mapping in evolutionarily diverse species. While full genome sequencing of mammals is rapidly progressing,the ability to assemble and align orthologous whole chromosomal regions from more than a few species is not yet possible. The intense focus on the building of comparative maps for domestic,laboratory and agricultural (cattle) animals has traditionally been used to understand the underlying basis of disease-related and healthy phenotypes.
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.
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.
Matthew Edward Hurles is director of the Wellcome Sanger Institute and an honorary professor of Human Genetics and Genomics at the University of Cambridge.
