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I. Introduction to Inherited Disorders

An inherited disorder, or a genetic disorder, is a problem caused by abnormalities in the human genome. These disorders are passed down from the offspring's parents' genes. Genetic disorders are commonly put into three categories: single-gene disorders, chromosomal disorders, and complex disorders.

Before we get started, let's go over some vocab.

Gene: A unit of genetic information that is transferred from parent to offspring.

Allele: An alternative form of a gene.

Locus: Fixed position on a chromosome where a gene is located.

Homologous: (of a chromosome) Pairs of chromosomes that consist of alleles of the same gene in the same loci in each chromosome.

Non-homologous: (of a chromosome) Chromosomes consisting of alleles of different genes.

Dominant: (of a gene) A gene that produces a phenotype in an organism, whether or not the allele is identical.

Recessive: (of a gene) Denoting heritable traits controlled by genes that are not overpowered by dominant characteristics inherited from one parent. Recessive genes are inherited from both parents.

Autosome: Any chromosome that is not a sex chromosome.

Sex chromosome: Any chromosome involved in determining the sex of an organism. (i.e. X and Y in humans)

Mutation: A change in the structure of a gene, resulting in a variant form that can be passed down to following generations. Mutations can be broken down into deletions, insertions, and base substitutions.

Deletion: The removal of a chromosomal segment.

Insertion: The insertion of a chromosomal segment.

Translocation: The movement of a chromosomal segment from one chromosome to another, non-homologous one.

Inversion: The reversal of a chromosomal segment within a chromosome.

Duplication: The repetition of a chromosomal segment.

Homozygous: (of an individual) Having two identical alleles of a gene or genes.

Heterozygous: (of an individual) Having two different alleles of a gene or genes.

Karyotype: the number and visual appearance of the chromosomes in the cell nuclei of an individual.

II. Single-Gene Disorders

A single gene disorder is exactly what it sounds like: a disorder caused by a single gene. This is an example of a Mendelian disorder. We can break this down into four categories:

Autosomal Dominant: This is a trait that means only one copy of a changed gene is needed to produce a certain phenotype. These gene changes are usually heritable, either from the parent or the parent's parent. In some cases, such as in a heterozygous carrier instance, a person can not express the phenotype of the disorder, but will still carry the risk of passing the trait down to their offspring. A person with an autosomal disorder has a 50% chance of passing it down to their offspring.
Examples of these diseases include Huntington disease, neurofibromatosis, and polycystic kidney disease.


Brain Scan of Huntington's Disease

Autosomal Recessive: This is a trait that is necessary for the offspring to have two copies of the changed to have the disorder. Each parent will contribute one copy of the gene to the offspring. The parents must each be heterozygous dominant/recessive, or homozygous recessive in order to carry or have a chance at passing down the changed gene. When both parents are carrier, each child has a 25% chance at having the disorder, a 50% chance at being a carrier, and a 25% chance of being neither a carrier nor express the phenotype.
Examples of these diseases include Cystic fibrosis, Sickle cell anemia, and Tay Sachs disease.


Illustration of Sickle cell anemia

X-linked dominant: This is a trait that follows a similar pattern to an autosomal dominant inheritance, only with this expression, more females are affected than males. This disorders are incredibly rare.
Examples of these diseases include Vitamin D resistance rickets, Rett syndrome, X-linked porphyria, and Fragile X syndrome.


Vitamin D Resistance Rickets

X-linked recessive: This is a trait that is most commonly seen in males, and is far more common than X-linked dominant traits. Individuals with these disorders do not have normal copies of the genes. Since males only have one X chromosome, the male will inherit the disorder upon this chromosome. These traits are passed down from the mother of the child. Females with the changed copy of the genes have a "backup" X chromosome, and therefore will become carriers of the disease instead of expressing the phenotype. Female carriers have a 25% chance of passing down the trait to her son, a 25% chance of having a son without the disorder, a 25% chance of having a carrier daughter, and a 25% chance of having a daughter who is not a carrier. Males with an X-linked recessive disorder will not pass this down to their sons, but 100% of his daughters will be carriers.
Exmaples of these diseases include Red-green color blindness and hemophilia.


Visual of Hemophilia

III. Chromosomal Disorders

A chromosomal disorder is defined as an abnormal condition due to a mutation in an individual's DNA.

Chromosomal disorders have two main types: Numerical, and structural.

Numerical chromosomal disorders are when there is a change in the number of chromosomes. The most severe chromosome disorders, those usually fatal, are caused by the loss or gain of whole chromosomes. Believe it or not, this kind of mutation can affect thousands of genes. Common types of numerical aberrations are triploidy, trisomy, monosomy, and mosaicism.

Structural chromosomal disorders result from breakages in the chromosomes, which can mean there may be more or less copies of a gene. See deletions, duplications, translocations, and inversions.


Translocation Mutation

The cause of chromosomal disorders are not well understood, however, we do understand that abnormalities occur during meiosis. Sometimes, abnormalities happen during gamete formation, and other abnormalities can happen after conception. Errors can occur in cell division (this is called nondisjunction) and call result in mutations.

Some chromosomal disorders can be inherited, while others are random accidents that occur during cell division or early fetal development.

Examples of chromosomal disorders include Down's syndrome (trisomy 21), Edward's syndrome (trisomy 18), Turner Syndrome (monosomy X), and Patau syndrome (trisomy 13).

Karyotype of Down Syndrome


Karyotype for Turner Syndrome

IV. Complex Disorders

Believe it or not, most genetic disorders are categorized under complex disorders. A complex disorder does not have a pattern of prediction or inheritance as seen in Mendelian gene disorders. Instead, these disorders are often influenced by environment.

A complex disorder is also called a multi-factorial disorder, which sounds exactly what it means: it is influenced by several factors. These can be genetic, environmental, or both. If an individual is predisposed to a disorder, often, an environmental or chemical (alcohol, drugs, stress, diet) trigger can "kick-start" the disorder.


Amyloid Positive Brain Scan

Close relatives of an individual with a multi-factorial genetic disorder have been shown to have a higher chance of developing the disorder rather than close relatives of someone who is not predisposed.


Fetal Progression of Spina Bifida

Examples of complex disorders include Alzheimer's, asthma, spina bifida, Parkinson Disease, and certain mental disorders such as bipolar disorder, schizophrenia, and schizoaffective disorder.


MRI of a Schizophrenic Brain

V. Credits and Further Reading:

Single Gene Disorders
Prenatal Testing for Single Gene Disorders
Chromosomal Abnormalities
Structural Abnormalities
What is Amyloid Positive?
Common Genetic Factors in Mental Disorders
Inheritance Pattern of Bipolar Disorder


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Pet Links:

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