Locus

In genetics, a locus is the position of a gene on a chromosome. Genes are located on chromosomes in a linear fashion, and each gene, or one of its alleles, have precise locations or loci on chromosomes. The exact chromosomal address of a gene may look something like “1p34.2”, where “1” designates the chromosome number, “p” designates the long arm or the short arm, and “34.2” is the exact location of the gene on that chromosomal arm. These numerical positions can be seen using a microscopically viewable ideogram of chromosomes that have been stained using one of several staining techniques like Giemsa Banding (G banding). By G-Banding chromosomes in metaphase, individual areas of chromosome absorb chemicals differently, giving chromosomes their banded appearance; then numbers and letters are used to pinpoint [Page 1028]exact locations of genes. If a higher-resolution banding is used, sub-bands and sub-sub-bands become visible. Sometimes, groups of genes occupy larger areas on chromosomes, and their location may be given as “11q14-q21” which is the OCA1 gene. This means that the genes extend from band q14 to band q21.

The distance between two loci is a very important parameter in clinical genetics. It gives us critical information on linkage between two or more genes, where linkage is the probability for neighboring alleles on a common chromosome to be transmitted together, as an intact unit, through meiosis. Linkage is the only method that allows us to create gene maps and trace disease genes along family generations. The distance between loci is the only predictor of genetic linkage.

Genetic distance is measured in units called centiMorgans (cM), which is defined as the genetic length over which, on average, one observes recombination 1 percent of the time. To measure distance between two loci, we need to know two variables: the recombination fraction between the two loci, and whether this recombination fraction deviates from 0.5. From these two variables, we can compute the lod score (Z) for “logarithmic of the odds.” Positive values of Z (odds>1) suggest the loci are linked, and negative values (odds<1) suggest loci are unlinked.

Genes located on a chromosome are not necessarily linked. These are called syntenic loci regardless of how far apart they are from each other, or how close together they lie on the chromosome. If two syntenic loci are so far apart that there is going to be at least one crossover between them with every meiosis, recombinant and nonrecombinant genotypes will occur in the offspring in equal proportions and the two loci will appear to be unlinked just as if the loci were on separate chromosomes. Locus heterogeneity is a situation in which identical clinical symptoms are caused by abnormalities at two or more genetic loci. If locus heterogeneity is unrecognized, it can confound genetic linkage analysis and give the false impression that a marker is unlinked to a disease locus when in fact it may be linked, but only in a subgroup of all families analyzed.