Why do genetic diseases occur

While many people are born with genes that increase their chances of developing certain cancers, these people never manifest the disease unless specific mutations occur during the course of their lifetime. For instance, mutations in the HPC1 gene on chromosome 1 have been linked to the development of prostate cancer. Although an individual with this mutation can develop a nonmalignant polyp at a fairly young age, prostate cancer will not metastasize to the man's other organs unless a number of other tumor suppressor genes are also partially or completely disabled.

Dozens of such genes have been identified to date, and researchers know that the expression of some of these genes is environmentally induced. Moreover, researchers have also noted that mutation events continue to occur after the disease phenotype has manifested, and these events are often responsible for the development of treatment resistance.

In contrast, due to the involvement of multiple genes and large variation in the severity of disease phenotype, very little is known about many of the more complex late-onset diseases, such as Alzheimer's disease and schizophrenia.

AD is the most common cause of dementia in the elderly, and it is characterized physically by the presence of amyloid plaques in the patient's brain and neurofibrillary tangles in his or her nervous tissue. Surprisingly, these plaques and tangles have also been found to a lesser extent in the healthy aging population , so it remains unclear whether they cause the neurological symptoms of AD or are merely side effects.

Recently, variation in the APOE gene, which is involved in fat metabolism , has been implicated in the formation of amyloid plaques. In healthy individuals, APOE signals the production of apolipoprotein E, which breaks down excess lipids throughout the body. This is not the case in individuals with Alzheimer's, although the exact mechanisms behind disease progression—including the role of APOE variation—are still a mystery.

To further complicate matters, additional gene mutations may also have a major effect in AD. In contrast, cases of AD that manifest after 60 years of age have been associated with a number of chromosomal regions, clearly suggesting the condition is a polygenic trait.

Similarly elusive are the genes involved in the onset of schizophrenia. In a commonly used method, researchers are trying to map these genes by considering their functional products. Several theories exist as to the biochemical causes of schizophrenia; the two main hypotheses involve glutamate and dopamine neurotransmitter systems Stefansson et al. Nonetheless, most scientists agree that there is a significant genetic component in schizophrenia. Indeed, genome-wide scans employed in the search for gene variants contributing to the disease have identified multiple loci, adding schizophrenia to the growing list of major late-onset disorders whose patterns are complex and poorly understood.

Beyond accumulated mutations, yet another mode of late-onset disease manifestation is through the accumulation of disease-causing agents that are produced from birth or alternatively, a lack of vital substances in the body due to genetic malfunctions. This accumulation can be a gradual process, producing an imbalance that goes unnoticed for decades. An example of this mode of affliction is Huntington's disease HD , an autosomal dominant neurodegenerative disorder that first shows symptoms in middle adulthood.

HD is characterized physiologically by a severe loss of neuronal tissue in the striatum, a structure in the brain that regulates movement and the cognitive aspects of behavior. At the molecular level, Huntington's is caused by a mutation in the HTT gene, which encodes a protein called huntingtin. So, if this mutation is present from birth, why are the symptoms of HD not evident until adulthood?

To answer this question, briefly consider the other molecular players involved in Huntington's—particularly the BDNF gene, which codes for the production of brain-derived neurotrophic factor BDNF , a protein that has a number of important functions in the adult central nervous system.

The age of HD onset is also controlled by a number of modifier genes that influence BDNF levels, but their influence is not currently understood beyond association. Interestingly, physical exercise and diet significantly increase BDNF levels in the brain, and such factors are therefore being investigated for their therapeutic value. As previously described, Huntington's disease is a highly penetrant single-gene disorder that manifests late in life.

Although HD is caused by a mutation in a single gene, recent research indicates that the timing of its onset, however inevitable, might be regulated by a number of modifier genes.

This sort of pattern of gene modification is even more complex in multifactorial genetic disorders, such as cancer and heart disease. In fact, these and other late-onset disorders show high levels of genetic variation—which is one of the reasons it is often challenging to forecast the onset and development of these conditions. This phenomenon has been attributed to the fact that the majority of late-onset disorders, by definition, manifest after people's reproductive years, thus avoiding the stringent selective constraints associated with sexual reproduction Wright et.

The genetic variation of late-onset disorders is also a result of the natural increase in mutation that occurs during the lifetime of any individual. Mutations arise and accumulate throughout a person's life, resulting in more potential loci that can interact to cause disease.

Recently, large studies examining genetic variation in thousands of individuals have identified the genes responsible for the most significant impacts on complex disease—in other words, the genes associated with the clearest phenotypes. However, these genome-wide association studies often overlook genetic modifiers of phenotype that have subtle or less penetrant effects due to the difficulties associated with identifying statistically significant variation in large populations.

Thus, one of the central challenges in the study of common adult diseases is the need to better delineate disease mechanisms to provide new insight for preventive approaches and therapeutic targets. Ezzati, M. The reversal of fortunes: Trends in county mortality and cross-county morality disparities in the United States.

Scientists are learning more and more about genetics. A worldwide research project called The Human Genome Project created a map of all human genes. It shows where the genes are located on the chromosomes.

Doctors can use this map to find and treat or cure some kinds of genetic disorders. There is hope that treatments for many genetic disorders will be developed in the future. Reviewed by: Amy W. Anzilotti, MD. Larger text size Large text size Regular text size. Children of either sex can be affected by this pattern of inheritance. X-linked or sex-linked recessive inheritance occurs when a mother carries the affected gene on one of her two X chromosomes and passes it to her son males always inherit an X chromosome from their mother and a Y chromosome from their father, while daughters inherit an X chromosome from each parent.

Sons of carrier mothers have a 50 percent chance of inheriting the disorder. Daughters also have a 50 percent chance of inheriting the defective gene but usually are not affected, since the healthy X chromosome they receive from their father can offset the faulty one received from their mother. Affected fathers cannot pass an X-linked disorder to their sons but their daughters will be carriers of that disorder.

Carrier females occasionally can exhibit milder symptoms of MD. Facebook Twitter YouTube Instagram. All rights reserved. The mutation changes the gene's instructions for making a protein, so the protein does not work properly or is missing entirely.

This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from one or both parents. A mutation can also happen during your lifetime. Genetic tests on blood and other tissue can identify genetic disorders. The information on this site should not be used as a substitute for professional medical care or advice.

Contact a health care provider if you have questions about your health. Genetic Disorders. See, Play and Learn No links available.