Down Syndrome

[Giovanni Maga]

In article <199505070644.BAA27486 at audumla.students.wisc.edu>,
afwagner at STUDENTS.WISC.EDU (Andrew Wagner) wrote:

> I have a number of questions on the genetics of Down Syndrome.
> 
> -What is the genetic basis/analysis of Down Syndrome?
> 
> -Why is it more prevalent in women of advanced maternal age?  Younger women
> can also have children with Down Syndrome and there is also a paternal
> factor in some cases.  What leads to the higher rate in AMA women?
> 
> Andrew Wagner

The genetics of Down syndrome is the presence of an extra copy of Chr.21.
This lead to unbalanced gene content with respect to normal people (which
have only two 21). Usually, trisomies and in general multisomies are
lethal, so you do not see the defect since the embryo dies before birth.
The 21 trisomy is viable but lead to more or less severe symptoms.

The higher prevalence in women older than 35-40 ys is due to the fact that
oocytes in women are stopped in the middle of meiosis and "restart" after
fertilization. Keeping this "frozen state" for 20-30 ys could lead to a bad
restart, which leads to abnormal chromosomal segregation. Of course it is
not only restricted to ama. It's just more probable. 

Diagnosis can be done by the analysis of the karyotype of the embryo (to
see if it carries the trisomy).
I do not know which paternal factors are involved.
Hope it helps. 
maga at vetbio.unizh.ch