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.
In genetics and bioinformatics, a single-nucleotide polymorphism is a germline substitution of a single nucleotide at a specific position in the genome that is present in a sufficiently large fraction of considered population.
A haplotype is a group of alleles in an organism that are inherited together from a single parent.
In population genetics, linkage disequilibrium (LD) is the non-random association of alleles at different loci in a given population. Loci are said to be in linkage disequilibrium when the frequency of association of their different alleles is higher or lower than expected if the loci were independent and associated randomly.
A DNA segment is identical by state (IBS) in two or more individuals if they have identical nucleotide sequences in this segment. An IBS segment is identical by descent (IBD) in two or more individuals if they have inherited it from a common ancestor without recombination, that is, the segment has the same ancestral origin in these individuals. DNA segments that are IBD are IBS per definition, but segments that are not IBD can still be IBS due to the same mutations in different individuals or recombinations that do not alter the segment.
Genetic association is when one or more genotypes within a population co-occur with a phenotypic trait more often than would be expected by chance occurrence.
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.
In molecular biology, SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA, is the most frequent type of variation in the genome. Around 335 million SNPs have been identified in the human genome, 15 million of which are present at frequencies of 1% or higher across different populations worldwide.
A tag SNP is a representative single nucleotide polymorphism (SNP) in a region of the genome with high linkage disequilibrium that represents a group of SNPs called a haplotype. It is possible to identify genetic variation and association to phenotypes without genotyping every SNP in a chromosomal region. This reduces the expense and time of mapping genome areas associated with disease, since it eliminates the need to study every individual SNP. Tag SNPs are useful in whole-genome SNP association studies in which hundreds of thousands of SNPs across the entire genome are genotyped.
In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.
Minor allele frequency (MAF) is the frequency at which the second most common allele occurs in a given population. They play a surprising role in heritability since MAF variants which occur only once, known as "singletons", drive an enormous amount of selection.
The 1000 Genomes Project, launched in January 2008, was an international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of at least one thousand anonymous participants from a number of different ethnic groups within the following three years, using newly developed technologies which were faster and less expensive. 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 Single Nucleotide Polymorphism Database (dbSNP) is a free public archive for genetic variation within and across different species developed and hosted by the National Center for Biotechnology Information (NCBI) in collaboration with the National Human Genome Research Institute (NHGRI). Although the name of the database implies a collection of one class of polymorphisms only, it in fact contains a range of molecular variation: (1) SNPs, (2) short deletion and insertion polymorphisms (indels/DIPs), (3) microsatellite markers or short tandem repeats (STRs), (4) multinucleotide polymorphisms (MNPs), (5) heterozygous sequences, and (6) named variants. The dbSNP accepts apparently neutral polymorphisms, polymorphisms corresponding to known phenotypes, and regions of no variation. It was created in September 1998 to supplement GenBank, NCBI’s collection of publicly available nucleic acid and protein sequences.
WGAViewer is a bioinformatics software tool which is designed to visualize, annotate, and help interpret the results generated from a genome wide association study (GWAS). Alongside the P values of association, WGAViewer allows a researcher to visualize and consider other supporting evidence, such as the genomic context of the SNP, linkage disequilibrium (LD) with ungenotyped SNPs, gene expression database, and the evidence from other GWAS projects, when determining the potential importance of an individual SNP.
In genetics, association mapping, also known as "linkage disequilibrium mapping", is a method of mapping quantitative trait loci (QTLs) that takes advantage of historic linkage disequilibrium to link phenotypes to genotypes, uncovering genetic associations.
A reference genome is a digital nucleic acid sequence database, assembled by scientists as a representative example of the set of genes in one idealized individual organism of a species. As they are assembled from the sequencing of DNA from a number of individual donors, reference genomes do not accurately represent the set of genes of any single individual organism. Instead a reference provides a haploid mosaic of different DNA sequences from each donor. For example, one of the most recent human reference genomes, assembly GRCh38/hg38, is derived from >60 genomic clone libraries. There are reference genomes for multiple species of viruses, bacteria, fungus, plants, and animals. Reference genomes are typically used as a guide on which new genomes are built, enabling them to be assembled much more quickly and cheaply than the initial Human Genome Project. Reference genomes can be accessed online at several locations, using dedicated browsers such as Ensembl or UCSC Genome Browser.
In genetics, haplotype estimation refers to the process of statistical estimation of haplotypes from genotype data. The most common situation arises when genotypes are collected at a set of polymorphic sites from a group of individuals. For example in human genetics, genome-wide association studies collect genotypes in thousands of individuals at between 200,000-5,000,000 SNPs using microarrays. Haplotype estimation methods are used in the analysis of these datasets and allow genotype imputation of alleles from reference databases such as the HapMap Project and the 1000 Genomes Project.
Imputation in genetics refers to the statistical inference of unobserved genotypes. It is achieved by using known haplotypes in a population, for instance from the HapMap or the 1000 Genomes Project in humans, thereby allowing to test for association between a trait of interest and experimentally untyped genetic variants, but whose genotypes have been statistically inferred ("imputed"). Genotype imputation is usually performed on SNPs, the most common kind of genetic variation.
SNV calling from NGS data is any of a range of methods for identifying the existence of single nucleotide variants (SNVs) from the results of next generation sequencing (NGS) experiments. These are computational techniques, and are in contrast to special experimental methods based on known population-wide single nucleotide polymorphisms. Due to the increasing abundance of NGS data, these techniques are becoming increasingly popular for performing SNP genotyping, with a wide variety of algorithms designed for specific experimental designs and applications. In addition to the usual application domain of SNP genotyping, these techniques have been successfully adapted to identify rare SNPs within a population, as well as detecting somatic SNVs within an individual using multiple tissue samples.
Yusuke Nakamura is a Japanese prominent geneticist and cancer researcher best known for developing Genome-Wide Association Study (GWAS). He is one of the world's pioneers in applying genetic variations and whole genome sequencing, leading the research field of personalized medicine.
