The discovery of the presence of fetal DNA (cell-free DNA) and fetal cells in maternal blood (Lo et al. 1997) has offered new approaches to non-invasive prenatal paternity testing (Wagner et al. 2009). The concentration of fetal DNA in maternal plasma was found to be much higher than that present in the cellular fraction. Since fetal DNA in maternal plasma circulates within the background of maternal DNA, it has been used mainly for non-invasive prenatal diagnosis of paternally inherited disorders as well as fetal gender testing.
By the use of Y-chromosomal sequences which are unique to a male fetuses a marker, a number of scientific groups were able to demonstrate that fetal DNA is indeed present in the plasma of pregnant women (Honda et al. 2001). The detection rate for fetal DNA in maternal plasma was much higher than that for DNA from nucleated blood cells extracted from a similar volume of whole blood. Using real-time quantitative polymerase chain reaction (PCR) technology, investigators have further demonstrated that fetal DNA is present at very high fractional concentrations in maternal plasma. The concentration of cell-free fetal DNA ranges from 3% to 12% of the total DNA found in the mother sample. This high relative concentration suggests that fetal DNA could be robustly detected in maternal plasma using modern molecular technology. This point has now been confirmed by many groups who have reported a close to 100% sensitivity at detecting fetal genetic material from maternal blood samples (Wei et al, 2001; Zhong et al, 2001; Bianchi 2004).
As it has been demonstrated that fetal cells can persist for years following delivery, a question has initially been raised regarding the possible persistance also of circulating fetal DNA from one pregnancy into the next, which may jeopardize the accuracy of a plasma based DNA test carried out during the second pregnancy. By serial monitoring of women following delivery, scientists have shown that cell-free fetal DNA is cleared very rapidly from maternal plasma following delivery, with a half-life in the order of minutes (Lo et al. 1999). These results indicate that unlike fetal cells in maternal blood, cell-free fetal DNA analysis is not complicated by the effects of persistance prior pregnancies. Thus, cell-free fetal DNA in maternal plasma can be a source of fetal genetic material for non-invasive genetic tests (Zhong et al 2001; Uitto et al. 2003; Sekizawa et al. 2007) as well as for non-invasive prenatal paternity DNA testing (Wagner et al. 2009).
To understand the differences between non-invasive (blood test) and invasive (CVS or amniocentesis) prenatal paternity tests, please review the following webpage:Comparison Table
References
Bianchi DW. Circulating fetal DNA: its origin and diagnostic potential—A Review. Placenta 2004; 25, Supplement A, Trophoblast Research, 18: S93–S101.
Honda H, Miharu N, Ohashi Y, Ohama K. Successful diagnosis of fetal gender using conventional PCR analysis of maternal serum. Clin Chem 2001; 47: 41-46.
Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS. Presence of fetal DNA in maternal plasma and serum. Lancet 1997; 350:485-487.
Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet 1999; 64: 218-224.
Samura O, Pertel B, Sohda S, Johnson KL, Sekizawa A, Falco VM, Elmes RS, Bianchi DW. Female fetal cells in maternal blood: use of DNA polymorphism to prove origin. Hum Genet 2000; 107: 28-32.
Sekizawa A, Purwosunu Y, Matsuoka R, Koide K, Okazaki S, Farina A, Saito H, Okai T. Recent advances in non-invasive prenatal DNA diagnosis through analysis of maternal blood. J Obstet Gynaecol Res. 2007; 33:747-764.
Uitto J., Pfendner E., Jackson LG. Probing the fetal genome: progress in non-invasive prenatal diagnosis. Trends in Molecular Medicine 2003; 9:339-343.
Wei C, Saller DN, Sutherland JW. Detection and quantification by homogeneous PCR of cell-free fetal DNA in maternal plasma. Clin Chem 2001; 47: 336-338.
Wagner J., Džijan S., Marjanović D., Lauc G. Non-invasive prenatal paternity testing from maternal blood. Int J Legal Med 2009; 123:75–79.
Zhong XY, Hahn S, Holzgreve W. Prenatal identification of fetal genetic traits. Lancet 2001; 357: 310-311.
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Non-invasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. New research ...
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