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PLAC4 gene polymorphisms in the Brazilian population

Grant number: 08/06853-7
Support Opportunities:Regular Research Grants
Duration: April 01, 2009 - March 31, 2011
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:José Eduardo Levi
Grantee:José Eduardo Levi
Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The discovery that fetal nucleic acids are present in the maternal plasma has opened a new venue for investigation of genetic characteristics of the fetus during pregnancy. In the last years at least two tests, based on this innovation, have gained the laboratorial setting; fetal gender and RhD determination, the former in any gestational age for both normal and at-risk pregnancies and the latter for RhD negative mothers. A non-invasive test for chromosomal abnormalities would be the "holy grail" of fetal medicine and enormous efforts were and are devoted to improving the detection of such genetic errors. Fetal DNA in maternal plasma is mostly cell-free what prevents the performance of karyotipic analysis in this material. A major hindrance is that fetal DNA represents a minor fraction of total plasma DNA, about 1-3%, in a background of 97-99% of maternal DNA, that are physically impossible to separate.Chinese investigators ingeniously circumvented this limitation by searching for sequences that would be derived only from the fetus. They focused on placental mRNA, which they also demonstrated to be present in maternal circulation. Among the few placental mRNAs detected, they chose those stemming from chromosome 21 and presenting the highest expression and containing single nucleotide polymorphisms (SNPs), in the studied population. In the case of a heterozygous fetus for one or more SNPs, they postulated that it would harbor a disbalance between SNPs presenting an extra copy of it. In this case they would be able to measure this 1:2 relationship (extra-copy) in comparison to a 1:1 relationship displayed by SNPs from chromosomes in normal dosage, also derived from placental mRNA present in maternal plasma. They were successful in this approach, when applying it to a series of pregnancies including mothers carrying Down's syndrome babies.The aim of this study is to sequence the PLAC4 gene from non-pregnant, unrelated individuals representative of the Brazilian population, intending to identify SNPs in this gene that are informative, i.e. their frequency is higher than 30%. Once SNPs are identified, in the future, we may test for their presence in the plasma of pregnant women, providing a potential non-invasive molecular test for this chromosomal abnormality which can be extended to other genetic diseases marked by abnormal chromosomal dosage such as chromosome 13 and 18 trissomies. (AU)

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