| MadSci Network: Genetics |
Here is a table showing the increasing risk of Down syndrome with increasing maternal age: http:// pregnancy.about.com/cs/downsyndrome/l/bldownssyn.htm Here is an equivalent table with some additional information: http:// www.nichd.nih.gov/publications/pubs/downsyndrome/down.htm The OMIM entry has excellent information: http:// www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190685 Most cases of Down syndrome involve trisomy of a free chromosome 21, rather than the inheritance of an extra copy of chromosome 21 through an aneuploid segregation from a translocation heterozygote. Getting an extra copy of an entire free chromosome 21 results from an error in meioisis called nondisjunction. In the first division of meiosis, both copies of chromosome 21 align and normally segregate from each other, delivering one copy of chromosome 21 to each pole. If this process fails, two copies go to one pole, and no copy goes to the other pole. This results in gametes (sperm or egg) that have two copies or no copies of chromosome 21 rather than the normal single copy. It is possible to detect, in individual cases of Down syndrome, whether the error was in the paternal meiosis or the maternal one. Studies show that the error is maternal over 95% of the time. This raises two questions: 1) why does the frequency increase with maternal age, and 2) why don't we see other human trisomies? The frequency rises with maternal age due to a peculiarity of meoisis in female mammals. Meiosis is originated in the fetal ovary, arresting at metaphase I with the homologous chromosomes aligned for segregation. Cells remain in this state until the time of ovulation, often decades later in humans. The longer cells remain in the arrested state, the greater the chance that there will be a nondisjunction event when meiosis resumes. The reason that we don't see other trisomies is that they are not compatible with fetal development (except XXY or XXX), so they generally do not survive to term. Presumably, there is an increase in the frequency of these individuals with increasing maternal age, but they are difficult to detect. You can read a good basic description of meiosis in the online books at: http:// www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books Terms used in this answer are defined in the MGI Glossary, from the link at: http:// www.informatics.jax.org/mgihome//help/help.shtml Yours, Paul Szauter Mouse Genome Informatics
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