Genetic Disorders 101Genes are the individual instructions carried in DNA (deoxyribonucleic acid) that tell our bodies how to develop and function; they govern our physical and medical characteristics, such as hair color, blood type and susceptibility to disease. A genetic disorder is a disease caused in whole or in part by a change in the normal DNA sequence. Genetic disorders can be caused by a mutation in one gene, by mutations in multiple genes, by a combination of gene mutations and environmental factors, or by damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes).
Researchers are discovering that nearly all diseases have a genetic component. Some diseases are caused by mutations that are inherited from the parents and are present in an individual at birth, like sickle cell disease. Other diseases are caused by acquired mutations in a gene or group of genes that occur during a person's life. Such mutations are not inherited from a parent, but occur randomly or due to some environmental exposure such as cigarette smoke, which causes cancer.
Genetic disorders typically involve the inheritance of a mutated disease-causing gene, such as sickle cell disease, cystic fibrosis, and Tay-Sachs disease. The mutated gene is passed down through a family, and each generation of children can inherit the gene that causes the disease.
Most genetic disorders are "multifactorial inheritance disorders," in which there is no single error but occur from a combination of variations in genes that together or in combination with environmental factors can result in a serious defect. Most multifactorial disorders cannot be diagnosed with PGD. Examples of such diseases include many common diseases, such as heart disease and diabetes.
Research has also shown that although many commonly occurring diseases are often caused by the inheritance of mutations in multiple genes at once, rare hereditary mutations in a single gene can be the cause. For example, breast cancer develops from gene mutations that cause or predispose members of a family and increase each family member's risk of developing a disease.
Single Gene DisordersA single gene disorder is the result of a single mutated gene. It is estimated that there are over 4000 human diseases caused by single gene defects that are passed on to subsequent generations. Some well-known single gene disorders include Tay-Sachs disease, cystic fibrosis, Duchenne muscular dystrophy, sickle cell anemia, Huntington disease, and hemophilia.
PGD has been successfully applied to a wide variety of single gene disorders. In single gene disorders where the gene structure is known, such as cystic fibrosis or Tay-Sachs, the actual genes of a sampled embryo are examined for the presence of the condition. In cases where the problematic gene is carried in just one gender, the DNA of the biopsied cell can be examined to determine the sex of the embryo and only female embryos replaced. For example, in Duchenne muscular dystrophy, only males are afflicted, though females can be carriers. So a family that carries this disorder would most likely select a male in order to avoid the transmission of the disease.
Chromosomal AbnormalitiesCells contain chromosomes, string-like structures that contain all of our genetic material. The building blocks of genes are DNA and the different patterns or sequence of DNA along the chromosome are codes for different genes. Humans have approximately 50,000 genes.
Genetic disease is caused by a change, or mutation, in the genetic code or an abnormal number of chromosomes. A chromosome abnormality reflects an abnormality of chromosome number or structure. Most chromosomal disorders can be diagnosed with PGD.
Chromosomal disorders refer to an excess or deficiency of a whole chromosome or chromosome segments. When there are an abnormal number of whole chromosomes, it is called aneuploidy. When a piece of one chromosome breaks off and reattaches to another chromosome this is a structural chromosome rearrangement and is called a translocation.
Chromosomal problems are common, affecting about 0.7 percent of live born infants and account for most early miscarriages. Down syndrome is usually associated with advanced maternal age and is a common example of aneuploidy. Down syndrome is caused by having an extra number 21 chromosome (three instead of two). It is also referred to as Trisomy 21. Age-related aneuploidy such as Down’s Syndrome is caused by errors in chromosomal separation during meiosis at the point of fertilization. Down Syndrome, also known as Trisomy 21 (an individual with Down Syndrome has three copies of chromosome 21, rather than two). Turner Syndrome is an example of monosomy, where a female is born with only one sex chromosome, an X.
The Science Behind Genetic DisordersGenetic defects occur when there are errors during meiosis or mitosis. Errors happen when the DNA is not copied accurately or when the chromosomes are not divided equally.
- Human cells contain 23 pairs or 46 chromosomes. These include chromosomes 1 to 22 (autosomes) and chromosomes X and Y (the sex chromosomes). Sperm and eggs undergo a process called meiosis in which the original 46 chromosomes are reduced to a new set of 23 single chromosomes (one from each chromosome pair).
- In the first step in meiosis the DNA is copied. This is followed by two sets of divisions that result in a cell that has 23 pairs of chromosomes. During this process there is a recombination of genes, which ensures that each sperm and egg contains a unique set of genes. When the egg and sperm fertilize, the embryo receives one chromosome of each pair from each parent resulting in a normal male (46, XY) or a normal female (46, XX).
- Meiosis in the sperm occurs throughout the man’s adult life. Meiosis in the egg begins in fetal life, but completes the final separation step just before and after fertilization. This waiting period may make the egg more vulnerable to age-related errors in meiosis. In the sperm, meiosis results in four sperm cells from each precursor cell, but in the egg, one egg extrudes the extra 23 chromosomes just outside the membrane of the egg, called the polar body, and only one egg is available for fertilization from the original cell.
- Mitosis is ordinary cell division. A cell with 46 chromosomes duplicates its chromosomes, and then divides. The cell division to create two new daughter cells.
Single Gene Disorders
- Single gene disorders are caused by changes (or mutations) in the DNA sequence of a gene. The mutated gene can be present on only one chromosome or on both chromosomes of a pair. Single gene disorders usually show a characteristic family history of a specific genetic disease and affect about 2 percent of the population. Genes are responsible for producing proteins that allow cells to work properly. Gene mutations alter the cell’s normal function due to a lack of a required protein. For example, the cystic fibrosis (CF) mutation affects a protein within the cell that reduces the cell’s ability to function properly. This results in a buildup of mucous within the lungs, the lungs cannot take in oxygen adequately and this can result in severe disability and death.
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