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Genetic Heterogeneity
Genetic heterogeneity occurs when disorders that appear to be similar are actually caused by mutations affecting different genes or different mutations affecting the same allele of a gene. Alzheimer's disease, kidney disease and many other diseases all contain a degree of genetic heterogeneity. The three main categories of genetic heterogeneity are: locus heterogeneity, allelic heterogeneity, and clinical heterogeneity.

Locus Heterogeneity
Locus heterogeneity is when different genes are affected by mutations, but individuals with mutations in different genes look physically similar. If this occurs, there is a good indication that the genes are connected in the same pathway. If certain genes share a similar pathway in which they all work together, a mutation to any of these genes has the potential to cause the same disorder.

Allelic Heterogeneity
Allelic heterogeneity is when different mutations affecting the same gene result in individuals looking physically similar. This arises when the same portion of a DNA sequence is changed as a result of a mutation or multiple mutations. Over the generations, the same sequence may again have a different alteration made to it. These changes build up over time and within individuals so that the same gene in different individuals can have different mutations, and yet all of the individuals will appear to look the same. An example of this is cystic fibrosis. Currently, there are 2000 mutations affecting the CFTR gene (cystic fibrosis transmembrane conductance regulator) that all result in an individual having cystic fibrosis.

Clinical Heterogeneity
Clinical heterogeneity is different from allelic heterogeneity in that different mutations to a single gene will result in individuals that appear physically different. An example of this involves mutations to a gene known as FGFR3 (fibroblast growth factor receptor 3). Different mutations to this gene result in varying diseases associated with abnormal bone growth.

Genetic Heterogeneity in Breast Cancer
A particular example of genetic heterogeneity is breast cancer. Currently, breast cancer kills more women than any other disease. Breast cancer can be caused by different mutations affecting specific genes (for example, BRCA1 and BRCA2), or it can be caused by different mutations affecting genes in similar pathways. As a result, breast cancer is not one specific disease, but is a group of many different diseases caused by mutations to different genes. Although breast cancer may arise as a result of a mutation to a specific gene, the variety of different mutations gives rise to different forms of breast cancer, each of which have their own specific risk factors, behaviours, and features. Because there is so much diversity amongst breast cancers, treatment varies from patient to patient.

Genetic heterogeneity is not only the cause of many breast cancers, but it is also found within the tumors themselves. Genetic heterogeneity can be found within a single tumor (intratumor heterogeneity), or it can be found between different tumors (intertumor heterogeneity). This heterogeneity is typically caused by genome instability. Genetic heterogeneity makes it difficult to treat diseases such as breast cancer because there are so many potential mutations that could cause the disease.