Genetic disorders are caused by differences in a person’s genetic material. Sometimes the difference is large and involves entire chromosomes. For example, a person might be born with an extra or missing chromosome, or there might be a large section of a chromosome added, missing, or moved to a different location in the genome. By examining a person’s karyotype many of these large chromosome abnormalities can be identified.
Often extra or missing chromosomes are caused by a process known as nondisjuction, occurring during cellular meiosis (the process that makes reproductive cells – eggs and sperm). Most human cells have a total of 46 chromosomes (23 pairs). Reproductive cells are an exception to this rule, with only 23 chromosomes (one copy of each pair). When sperm fertilizes an egg, the resulting zygote will have the typical 46 chromosomes and both the sperm and the egg will have contributed equal amounts of genetic information. During meiosis, the chromosome pairs line up along the middle of the cell in metaphase and separate during anaphase. Nondisjunction occurs when a chromosome pair does not separate properly, resulting in a reproductive cell with two copies of that particular chromosome (instead of the typical one) and another reproductive cell to not have any copies of that chromosome. This situation will result in sperm/egg cells with 22 and 24 chromosomes rather than the typical 23.
If one of these abnormal sperm/egg cells goes through fertilization, the embryo that forms will have either a missing or extra chromosome with a total of 45 or 47 chromosomes, respectively. It is well known that nondisjuction occurs much more frequently during egg cell formation that in sperm cell formation, and that the chance of it occurring increases as a woman gets older.
Many times an embryo with an extra or missing chromosome will not be viable with life and will miscarry, often early in pregnancy before a woman would even know she is pregnant. It is estimated that around 10-30% of fertilized eggs have a chromosome abnormality; while only about 0.3% of live born babies have an extra/missing chromosome. However, there are some chromosomes that can be missing or extra and be viable with life. An extra or missing copy of a chromosome results in an extra or missing copy of each gene found on that chromosome. Therefore, extra/missing chromosomes that are viable are typically the smallest chromosomes that have the least amount of genetic material (genes) on them.
Because each chromosome holds a different set of genes, the effects of extra/missing chromosomes vary depending on which chromosome is involved. Some common examples of genetic syndromes caused by extra or missing chromosomes include Down Syndrome (extra chromosome 21), Edward Syndrome (extra chromosome 18), and Turner Syndrome (missing X chromosome). Trisomy is the term given for having three copies of a particular chromosome (i.e. Down Syndrome is also commonly called Trisomy 21). Alternatively, monosomy is the term describing only having one copy of a particular chromosome (i.e. Turner Syndrome is Monosomy X).
Another less common chromosome abnormality is a chromosome rearrangement. In this case, the change in genetic information does not involve entire chromosomes, but sections of chromosomes. Rearrangements can exist either in a balanced or unbalanced form. Balanced rearrangements occur when the location of genetic information has been moved but no information has been lost or added (i.e. a section of 2 different chromosomes have switched places). Unbalanced rearrangements indicate both that genetic information has moved and that some genetic information has either been lost or gained. Rearrangements can involve a single chromosome or multiple chromosomes.
Examples of chromosome rearrangements are insertions (section of genetic information added to a chromosome), deletions (section of genetic information removed), inversions (section of a chromosome oriented backwards/reversed), and translocations (chromosome section moved to a different location). Chromosome structural rearrangements are more likely to occur during meiosis in males than in females. This is in contrast to nondisjunction (described above) which occurs more often during female meiosis.
There are two types of translocations: reciprocal and robertsonian. In reciprocal translocations of any two chromosomes exchange information (see illustration below). In a robertsonian translocation, the long arms of two acrocentric chromosomes fuse together. The acrocentric chromosomes are chromosomes 13-15, 21 and 22 which all have their centromere very close to one end of the chromosome. This results in a very short “short arm” of the chromosome, containing very few gene sequences. Therefore when the two long arms fuse, and the short arms are lost, there is very little loss of information.
A person with a balanced rearrangement will typically not have any physical differences or symptoms because there has not been net gain or loss of information. These people are considered “balanced translocation carriers” because there is a risk for their children to inherit an unbalanced rearrangement which could cause physical differences and medical problems. Large chromosome rearrangements are also easily observed by studying a person’s karyotype.
|Left: This picture illustrates an example of a translocation. A portion of chromosome 4 and a portion of chromosome 20 switch places. In this case no information was actually lost.
“Translocation.” National Human Genome Research Institute. 2008. National Institutes of Health. 10 December 2008.http://www.genome.gov/Pages/Hyperion/DIR/VIP/Glossary/Illustration/translocation.cfm?key=translocation