MadSci Network: Genetics

Re: Why does rate of Down Syndrome increase with maternal age?

Date: Mon Jul 18 11:57:04 2005
Posted By: Paul Szauter, Staff, Mouse Genome Informatics
Area of science: Genetics
ID: 1120023311.Ge

Here is a table showing the increasing risk of Down syndrome with increasing maternal age:

Here is an equivalent table with some additional information:

The OMIM entry has excellent information:

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:

Terms used in this answer are defined in the MGI Glossary, from the link at:


Paul Szauter
Mouse Genome Informatics

Current Queue | Current Queue for Genetics | Genetics archives

Try the links in the MadSci Library for more information on Genetics.

MadSci Home | Information | Search | Random Knowledge Generator | MadSci Archives | Mad Library | MAD Labs | MAD FAQs | Ask a ? | Join Us! | Help Support MadSci

MadSci Network,
© 1995-2005. All rights reserved.