Genetics 101

What Causes Genetic Defects? Cells contain chromosomes, which are string-like structures where all of our genetic material resides. The genetic material is called a gene. Genes are made up of DNA sequences. Each cell has approximately 30,000 genes. Genetic disease is caused by abnormalities of gene function. This can occur by having too many or too few chromosomes (aneuploidy), when chromosome pieces are attached to the wrong chromosome (translocation), when one is missing a piece of a chromosome (deletion), when part of a chromosome is upside down (inversion), or when the gene's DNA sequence is changed.

Chromosome Abnormalities
Chromosome abnormalities, such as aneuploidy or structural chromosome rearrangements, are responsible for most genetic diseases. Most cells contain 23 pairs or 46 chromosomes. These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes). Sperm and eggs only contain 23 single chromosomes (one from each chromosome pair). During fertilization, the embryo receives one chromosome of each pair from each parent resulting in a normal male (46,XY) or a normal female (46,XX). If the sperm or egg harbors a chromosome abnormality, this can be transmitted to the embryo resulting in a genetic disorder.

In the IVF setting and in natural conception, chromosomally abnormal embryos have a low implantation rate and if they do implant the pregnancy often results in miscarriage or the birth of a baby with physical problems, developmental delay and/or mental retardation. Chromosome disorders occur in well over half of all first trimester pregnancy losses.

Down Syndrome is usually associated with advanced maternal age and is a common example of aneuploidy. Down Syndrome is caused by having an extra #21 chromosome (3 instead of 2). It is also referred to as trisomy 21.

Single Gene Abnormalities
Single gene abnormalities (mutations) are caused by changes in the DNA sequence of a gene. Genes produce proteins that make our cells work properly. Single gene disorders usually show a characteristic family history of a specific genetic disease. Gene mutations can alter the cells normal function due to a lack of a required protein. For example, Cystic Fibrosis (CF) is a common genetic disorder that primarily affects the lungs of CF patients. The CF mutation affects a protein within the cell that reduces the cells ability to function properly. This results in a build up of mucus within the lungs, lung dysfunction and possible death.