Re: What are the causes of Down's syndrome?

The simplest answer to your question is...we don't know for sure what gene(s) causes Down syndrome.But here's some background and some speculation...

Down syndrome is the most common form of mental retardation caused by chromosomal abberation. The disease results from having three copies of all or a portion of chromosome 21 (trisomy 21). The risk of having a liveborn with Down syndrome increases with the mother's age, from 1 in 1000 at age 30 to 9 in 1000 at age 40. Most cases (~95%) of Down syndrome result from the presence of an intact extra copy of chromosome 21; however, translocation of a 1 copy of a critical region of this chromosome to another acrocentric chromosome (most often chromosome 14) can also lead to Down syndrome.

Trisomy 21 is overwhelmingly caused by errors during meiosis (mostly nondisjunction or failure of the paired chromosomes to separate) during production of the egg in the mother. It is thought that failure to recombine during meiosis I could lead to nondisjunction.In a small number of cases, Down syndrome results from the translocation of a small portion of chromosme 21 to another chromosome, thus this small portion of the chromosome is present in three copies in the cell. It is these cases that are very informative regarding what gene or genes may play a role in the disease.

An ~ 5,000,000 base pair region of the q arm of chromosme 21 called DCR (for Down syndrome Critical Region) has been associated with cases of partial trisomy 21 and in particular, a subregion located in band 21q22.3 appears to be associated with mental retardation and a number of morphological features of individuals with Down syndrome. A previously uncharacterized gene called DSCR1 has been found that is expressed in fetal brain and heart tissue. It has been suggested that DSCR1 may encode a transcription factor or protein that regulates the expression of other gene(s) or that DSCR1 may encode a protein involved in internal communication (signal transduction) in the cell. Overexpression of proteins such as these during fetal development might result in the mental retardation and additional abnormalities associated with Down syndrome. A second gene called DCRB has also been isolated rom the larger Down syndrome critical region of chromosme 21; it's function is unknown, but it is mainly expressed in human placenta, so it is also possible that this gene is associated with the disease. Remember, the DCR is ~ 5 million base pairs (roughly the size of the entire chromosme of most bacteria), so many genes could still be in this region, yet not be characterized.

For more info on the genetics Down syndrome, visit the Online Mendelian Inheritence in Man program at the National Center for Biotechnology Information
http://www.ncbi.nlm.nih.gov/omim/

You can search the database using keywords like Down syndrome or you can use the locus 21q22.3.