Down syndrome is a chromosomal abnormality that affects human chromosome 21, and occurs in about 1 in 800 live births. The most common type is known as Trisomy 21, which results from a nondisjunction event during meiosis. Meiosis occurs in such a way that the affected gamete receives two copies of chromosome 21 instead of just the usual one copy. When fertilization occurs with another normal gamete, the resulting zygote then contains three copies of the chromosome - hence the name Trisomy 21. Other common types of Down syndrome include Mosaicism, where nondisjunction occurs after fertilization, so that only some cells in the body contain the extra 21st chromosome. Robertsonian translocation is another, and it occurs when one of the parents of the affected individual has part of their chromosome 21 attached to chromosome 14 or 15. This often results in an uneven distribution of chromosome 21 in their gametes.
Why chromosome 21? Because it is the smallest of all the human chromosomes, it is believed that it is more likely to become 'lost' in the process of meiotic division. In addition, the risk of developing Down syndrome spikes if the individual's mother is over the age of 40, as the likelihood of error during meiosis increases with age.
Common physical characteristics of DS-affected individuals include a round face, flattened profile, almond shaped eyes, and short stature. They may also have reduced intellectual capacity, though this varies greatly from person to person. Many are at risk for developing congenital heart defects. It may seem like common sense to assume that defects like these are a product of gene overexpression - there is an entire extra chromosome at work here. In the study cited below, scientists have found that microRNA-155, located on chromosome 21, is in fact overexpressed in heart and brain cells; but its overexpression leads to the underexpression of the transcription factor MeCP2, which controls the expression of several genes. Their study with mice has shown that the amount of protein can be raised to a normal level by treatment with a drug called antagomir.
Reference: Ohio State University. "New Theory of Down Syndrome Cause May Lead to New Therapies." ScienceDaily 24 March 2010. 25 March 2010 <http://www.sciencedaily.com /releases/2010/03/100323121839.htm>.
Photo credit: Human male karyotype showing three copies of chromosome 21. University of New South Wales Embyology. Can be found here.
Linda Le is a contributing writer on biomedical research to TuftScope for Spring 2010.
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