A person’s genome contains all the instructions needed for life. If you think of the genome as a detailed city map, each location has a unique address. In genetics, this address is called a genomic locus, which is a specific, physical position on a chromosome. This precise point allows scientists to find and study genes and other significant DNA sequences, providing a framework for exploring how genetic information is organized and inherited.
Defining a Genomic Locus
A genomic locus is a fixed position on one of the 23 pairs of chromosomes in human cells. This location is constant from person to person, providing a universal reference point for geneticists. The complete ordered list of known loci for a particular genome forms what is called a genetic map, which is essential for navigating our DNA. Each locus represents a particular segment of the DNA sequence.
A gene, which is a segment of DNA containing instructions for making a protein, occupies a specific locus. The term locus is broader, however, as it can refer to the location of any DNA sequence. This includes areas with regulatory functions that control gene activity or segments used as genetic markers for research.
On a pair of homologous chromosomes, inherited from each parent, there can be different versions of the same DNA sequence at a given locus. These variations are called alleles. For instance, a locus for eye color might have an allele for brown eyes and another for blue eyes. An individual is homozygous for that locus if they have two identical alleles and heterozygous if the alleles are different.
Mapping and Identifying Loci
Scientists use a precise coordinate system to describe the location of any locus. This genetic address begins with the chromosome number (1-22, or X and Y). Each chromosome has a centromere that divides it into a short arm (“p”) and a long arm (“q”). Staining reveals a unique pattern of bands, which are numbered outward from the centromere. A complete locus designation, like 11p15.4, indicates chromosome 11, on the short arm (p), at band 15, sub-band 4.
Genetic linkage analysis finds loci by tracking the inheritance of a chromosome region and a trait through multiple generations of a family. If a specific locus is consistently inherited by family members who share the trait, the responsible gene is likely located at or near that locus. This method is effective for identifying genes that cause single-gene disorders.
Genome-Wide Association Studies (GWAS) scan the genomes of thousands of unrelated individuals, comparing a group with a specific disease to a control group. Researchers look for genetic markers, like single-nucleotide polymorphisms (SNPs), that appear more frequently in the group with the trait. This statistical association points to a genomic locus involved in the trait or disease.
Functional Significance of Loci
The function of a locus is determined by the biological role of the DNA sequence it contains. These locations can be categorized based on the information they hold and how that information is used by the cell.
Protein-coding loci contain genes, the blueprints for building proteins. Proteins perform a vast array of tasks, from catalyzing reactions to providing structural support. The DNA sequence at a protein-coding locus dictates the amino acid sequence and function of a specific protein.
Regulatory loci do not code for proteins but act like switches to control the activity of other genes. They determine when, where, and how much of a protein is made by binding to proteins that enhance or suppress gene expression. Examples include promoters, which initiate gene transcription, and enhancers, which can significantly boost gene activity even from a distance.
Non-coding RNA loci are transcribed into RNA molecules that are not translated into proteins but have other jobs. These functional RNAs participate in processes like guiding protein synthesis or regulating gene expression. Examples include microRNAs and long non-coding RNAs.
Loci in Health and Disease
The specific allele present at a genomic locus can have significant consequences for an individual’s health. These genetic variations are central to understanding both rare and common diseases, from being the sole cause of a condition to contributing a small amount to overall risk.
In single-gene disorders, a mutation at a single locus is responsible for causing a disease. For example, sickle cell anemia results from a mutation at the HBB gene locus on chromosome 11. This gene provides instructions for making part of hemoglobin, and the mutation leads to abnormal protein, causing red blood cells to become misshapen and block blood flow.
Most common human diseases, like type 2 diabetes and heart disease, are complex or polygenic traits. They are influenced by variations at many different loci across the genome, with each variant contributing a small effect to the overall risk. GWAS has identified hundreds of such loci for various conditions, implicating genes involved in processes like insulin secretion and glucose metabolism.