Association mapping
Encyclopedia
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 phenotype
s (observable characteristics) to genotype
s (the genetic constitution of organisms).
, than outside of it. Association mapping thus asks if a particular genetic marker
(most often a SNP) is more common in a particular phenotype than you would expect by chance. It is most often performed by scanning the entire genome for significant associations between a panel of SNPs (which, in many cases are spotted onto glass slides to create “SNP chips
”) and a particular phenotype. These associations must then be independently verified in order to show that they either a. contribute to the trait of interest directly, or b. are linked to/ in linkage disequilibrium with a quantitative trait locus (QTL) that contributes to the trait of interest.
s. Association mapping has been most widely applied to the study of human disease, specifically in the form of a genome-wide association study
(GWAS). A genome-wide association study is performed by scanning an entire genome for SNPs associated with a particular trait of interest, or in the case of human disease, with a particular disease of interest. To date, thousands of genome wide associations studies have been performed on the human genome in attempt to identify SNPs associated with a wide variety of complex human diseases (e.g. cancer
, Alzheimer’s disease, and obesity
). The results of all such published GWAS are maintained in an NIH database (figure 1). Whether or not these studies have been clinically and/or therapeutically useful, however, remains controversial.
Linkage disequilibrium
In population genetics, linkage disequilibrium is the non-random association of alleles at two or more loci, not necessarily on the same chromosome. It is also referred to as to as gametic phase disequilibrium , or simply gametic disequilibrium...
mapping", is a method of mapping quantitative trait loci
Quantitative trait locus
Quantitative traits refer to phenotypes that vary in degree and can be attributed to polygenic effects, i.e., product of two or more genes, and their environment. Quantitative trait loci are stretches of DNA containing or linked to the genes that underlie a quantitative trait...
(QTLs) that takes advantage of historic linkage disequilibrium to link phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s (observable characteristics) to genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
s (the genetic constitution of organisms).
Theory
Association mapping is based on the idea that traits that have entered a population only recently will still be linked to the surrounding genetic sequence of the original evolutionary ancestor, or in other words, will more often be found within a given haplotypeHaplotype
A haplotype in genetics is a combination of alleles at adjacent locations on the chromosome that are transmitted together...
, than outside of it. Association mapping thus asks if a particular genetic marker
Genetic marker
A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
(most often a SNP) is more common in a particular phenotype than you would expect by chance. It is most often performed by scanning the entire genome for significant associations between a panel of SNPs (which, in many cases are spotted onto glass slides to create “SNP chips
SNP genotyping
SNP genotyping is the measurement of genetic variations of single nucleotide polymorphisms between members of a species. It is a form of genotyping, which is the measurement of more general genetic variation. SNPs are one of the most common types of genetic variation...
”) and a particular phenotype. These associations must then be independently verified in order to show that they either a. contribute to the trait of interest directly, or b. are linked to/ in linkage disequilibrium with a quantitative trait locus (QTL) that contributes to the trait of interest.
Use
The advantage of association mapping is that it can map quantitative traits with high resolution in a way that is statistically very powerful. Association mapping, however, also requires extensive knowledge of SNPs within the genome of the organism of interest, and is therefore difficult to perform in species that have not been well studied or do not have well-annotated genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s. Association mapping has been most widely applied to the study of human disease, specifically in the form of a genome-wide association study
Genome-wide association study
In genetic epidemiology, a genome-wide association study , also known as whole genome association study , is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait...
(GWAS). A genome-wide association study is performed by scanning an entire genome for SNPs associated with a particular trait of interest, or in the case of human disease, with a particular disease of interest. To date, thousands of genome wide associations studies have been performed on the human genome in attempt to identify SNPs associated with a wide variety of complex human diseases (e.g. cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, Alzheimer’s disease, and obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
). The results of all such published GWAS are maintained in an NIH database (figure 1). Whether or not these studies have been clinically and/or therapeutically useful, however, remains controversial.