cosegregation

Cosegregation is the non-random transmission of genetic variants or markers from parents to offspring, such that they are inherited together more often than would be expected by chance. It most commonly occurs for loci that are physically close on the same chromosome, a situation known as genetic linkage. Cosegregation is observed in family pedigrees and is a fundamental concept behind linkage analysis, which is used to map the location of disease genes relative to genetic markers.

The strength of cosegregation depends on how often recombination occurs between the loci during meiosis. The recombination fraction, theta, ranges from 0 to 0.5, with theta near 0 indicating tight linkage and strong cosegregation, and theta near 0.5 indicating independent assortment. In practice, complete cosegregation (theta = 0) is rare; most apparent cosegregation is partial due to occasional recombination, as well as factors such as incomplete penetrance or phenocopies. Linkage analysis uses statistical measures, such as LOD scores, to compare the likelihood of the observed inheritance pattern under linkage versus no linkage.

Applications of cosegregation include locating disease-associated regions in the genome, refining candidate intervals, and supporting the pathogenic role of a variant by its co-transmission with the disease through multiple informative meioses. Limitations arise from recombination events, marker informativeness, population structure, and phenotypic variability. Cosegregation is distinct from linkage disequilibrium, which describes non-random association of alleles at different loci at the population level rather than within families.

See also: genetic linkage, recombination, linkage analysis, cosegregation analysis, linkage disequilibrium.