Genetic Disorder

What are Genetic Disorders?

A genetic disorder is an illness caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due in part to a genetic disorders, they can also be caused by environmental factors. Most disorders are quite rare and affect one person in every several thousands or millions. Some types of recessive gene disorders confer an advantage in the heterozygous state in certain environments.

As we unlock the secrets of the human genome, we are learning that nearly all diseases have a genetic component. Some, including many cancers, are caused by a mutation in a gene or group of genes in the cells of an individual. Such mutations can occur randomly or due to some environmental exposure (such as cigarette smoke).

Other genetic disorders are hereditary - such as Huntington disease or Marfan's disease - where a mutated gene is passed down through a family and each generation of children can inherit the gene that causes the disease.

But most genetic disorders are "multifactorial inheritance disorders," meaning they are caused by a combination of small variations in genes, often in concert with environmental factors.

Through research on the human genome, we now know that many common diseases usually caused by genetic alterations in the genes of an individual's cells - such as breast cancer and colon cancer - also have rare hereditary forms. In these cases, gene variants that cause or strongly predispose a person to these cancers run in a family and significantly increase each member's risk of developing the disease.

Geneticists group genetic disorders into three categories:
Single gene disorders are caused by a mutation in a single gene. The mutation may be present on one or both chromosomes (one chromosome inherited from each parent). Sickle cell disease, cystic fibrosis and Tay-Sachs disease are examples of single gene disorders.

Chromosome disorders are caused by an excess or deficiency of the genes that are located on chromosomes, or structural changes within chromosomes. Down syndrome, for example, is caused by an extra copy of chromosome 21, but no individual gene on the chromosome is abnormal.

Multifactorial inheritance disorders are caused by a combination of small variations in genes, often in concert with environmental factors. Heart disease and most cancers are examples of these disorders. Behaviors are multifactorial, complex traits involving multiple genes that are affected by a variety of other factors. Researchers are learning more about the genetic contribution to behavioral disorders such as alcoholism, obesity, mental illness and Alzheimer disease. There is currently no recommended genetic testing for behavioral disorders such as alcoholism or obesity.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Genetic disorder" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Multifactorial And Polygenic (Complex) Genetic Disorder

Genetic disorders may also be complex, multifactorial or polygenic, this means that they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Multifactoral disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified.

On a pedigree, polygenic diseases do tend to “run in families”, but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure).

  • asthma
  • autism
  • autoimmune diseases such as multiple sclerosis
  • cancers
  • ciliopathies
  • cleft palate
  • diabetes
  • heart disease
  • hypertension
  • inflammatory bowel disease
  • mental retardation
  • obesity

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Genetic disorder" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Single Gene Genetic Disorder

Prevalence of some single gene disorders
DisorderPrevalence
Autosomal dominant
Familial hypercholesterolemia1 in 500
Polycystic kidney disease1 in 1250
Huntington disease1 in 2,500
Hereditary spherocytosis1 in 5,000
Marfan syndrome1 in 20,000
Autosomal recessive
Sickle cell anemia1 in 625
(African Americans)
Cystic fibrosis1 in 2,000
(Caucasians)
Tay-Sachs disease1 in 3,000
(American Jews)
Phenylketonuria1 in 12,000
Mucopolysaccharidoses1 in 25,000
Glycogen storage diseases1 in 50,000
Galactosemia1 in 57,000
X-linked
Duchenne muscular dystrophy1 in 7,000
Hemophilia1 in 10,000
Values are for liveborn infants

A single gene disorder is the result of a single mutated gene. There are estimated to be over 4000 human diseases caused by single gene defects. Single gene disorders can be passed on to subsequent generations in several ways. Genomic imprinting and uniparental disomy, however, may affect inheritance patterns. The divisions between recessive and dominant types are not "hard and fast" although the divisions between autosomal and X-linked types are (since the latter types are distinguished purely based on the chromosomal location of the gene). For example, achondroplasia is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe skeletal disorder that achondroplasics could be viewed as carriers of. Sickle-cell anemia is also considered a recessive condition, but heterozygous carriers have increased immunity to malaria in early childhood, which could be described as a related dominant condition.

Autosomal dominant

Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. There is a 50% chance that a child will inherit the mutated gene. Conditions that are autosomal dominant often have low penetrance, which means that although only one mutated copy is needed, a relatively small proportion of those who inherit that mutation go on to develop the disease. Examples of this type of disorder are Huntington's disease, Neurofibromatosis 1, Marfan Syndrome, Hereditary nonpolyposis colorectal cancer, and Hereditary multiple exostoses, which is a highly penetrant autosomal dominant disorder. Birth defects are also called congenital anomalies.

Autosomal recessive

Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder. Examples of this type of disorder are cystic fibrosis, sickle-cell disease (also partial sickle-cell disease), Tay-Sachs disease, Niemann-Pick disease, spinal muscular atrophy, and Dry (otherwise known as "rice-brand") earwax.

X-linked dominant

X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets. Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions such as Rett syndrome, Incontinentia Pigmenti type 2 and Aicardi Syndrome are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter Syndrome (47,XXY) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of a female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they receive their father's Y chromosome), and his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected fetus with each pregnancy, although it should be noted that in cases such as Incontinentia Pigmenti only female offspring are generally viable. In addition, although these conditions do not alter fertility per se, individuals with Rett syndrome or Aicardi syndrome rarely reproduce.

X-linked recessive

X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. A woman who is a carrier of an X-linked recessive disorder (XRXr) has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene and are therefore carriers. Examples of this type of disorder are Hemophilia A, Duchenne muscular dystrophy, red-green color blindness, Muscular dystrophy and Androgenetic alopecia.

Y-linked

Y-linked disorders are caused by mutations on the Y chromosome. Because males inherit a Y chromosome from their fathers, ''every'' son of an affected father will be affected. Because females inherit an X chromosome from their fathers, female offspring of affected fathers are ''never'' affected.

Since the Y chromosome is relatively small and contains very few genes, there are relatively few Y-linked disorders. Often the symptoms include infertility, which may be circumvented with the help of some fertility treatments. Examples are Male Infertility and hypertrichosis pinnae.

Mitochondrial

This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children. An example of this type of disorder is Leber's Hereditary Optic Neuropathy.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Genetic disorder" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.