Linkage disequilibrium questions

Francesco Zito ZITO at CMNS.MNEGRI.IT
Tue Jul 11 08:47:52 EST 1995


Hello!

My name is Franco and I have been involved in the field of epidemiology
and molecular biology for few months. The purpose of my research group
is to perform a case-control study on a multifactorial disease, such as
myocardial infarction, on the basis of different genotypes among an
Italian population. Differences, or "polymorphism", at different
genetic  loci (such as at all known risk factors for myocardial
infarction genetic sites) is one of the topics of my group.

Anyway, I have some unsolved questions and I would appreciate very much
if someone helped me suggesting appropriate literature (sendind
correctly references) or directly answering me by e-mail. 

Which are the mathematical basis of the "linkage disequilibrium"? Which
are the parameters considered in the analysis?  
I don't understand, in a correct and simple way, the methods to analyze
DNA changes on the basis of "polymorphic sites" (already linked,
previously, to the disease!) more or less in linkage disequilibrium.
Why the concept of genetic "co-segregation" is so closely connected to
linkage disequilibrium?
An important question is: which would be your guide-lines in a
situation as the following?!? Three polymorphisms, of the genetic loci
which I am studying, had been verified to be in strong linkage
disequilibrium; in my data, anyway, one of them is present in a
different frequency among an healthy population and a diseased
population. Cosegregation of two alleles so closely one another doesn't
seem to exist?!? Is it possible that two markers of segregation, such
as two closely sites of the genetic site, are in "partial" linkage
disequilibrium? The difference of allelic frequency among healthy and
diseased populations at the two sites is stathistically significant,
and I don't know how to solve the problem in a logical way..
Please, help me and excuse me if I have not been clear enough!  



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