Technology Behind Non Invasive Prenatal DNA Testing on Maternal Blood

The discovery of the presence of fetal cells in maternal blood (Bianchi 1990; Ganshirt et al. 1994; Adkinson et al. 1994)  has offered new approaches to non-invasive prenatal paternity testing that was originally developed by our company during a number of years and offered to the general public in year 2001. Since fetal cells in maternal blood circulate within the background of maternal cells, it has been used mainly for non-invasive prenatal diagnosis of paternally inherited disorders as well as fetal gender testing. On this figure we can see fetal cells colonies under microscope.

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 cells is indeed present in the blood of pregnant women (Geifman-Holtzman et al. 1995). Using real-time quantitative polymerase chain reaction (PCR) technology, investigators have further demonstrated that fetal cells is present at relatively high fractional concentrations in maternal blood. This concentration suggests that fetal cells could be robustly detected in maternal blood 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. Thus, fetal cells in maternal blood can be a source of fetal genetic material for non-invasive genetic tests (De La Cruz et al. 1995; Samura et al. 2000; 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

Adkinson et al. Improved detection of fetal cells from maternal blood with polymerase chain reaction. Am. J. Obstetrics Gynecology 1994; 170: 952-955.

Bianchi et al. Isolation of fetal DNA from nucleated erythrocytes in maternal blood. Proc. Natl. Acad. Sci. 1990; 87:3279-3273..

De La Cruz et al. Prenatal diagnosis by use of fetal cells isolated from maternal blood. Am. J. Obstetrics Gynecology 1995; 173: 1354-1355.

Ganshirt et al. Fetal cells in maternal circulation throughout gestation. Lancet 1994; 343: 1038-1039.

Geifman-Holtzman et al. Detection fetal HLA-DQ alpha sequences in maternal blood: a gender-independent technique of fetal cells identification. Prenatal Diagnosis 1995; 15: 261-268.

Samura et al.. Female fetal cells in maternal blood: use of DNA polymorphism to prove origin. Hum Genet 2000; 107: 28-32.

Sekizawa et al.. Recent advances in non-invasive prenatal DNA diagnosis through analysis of maternal blood. J Obstet Gynaecol Res. 2007; 33:747-764.

Uitto et al. Probing the fetal genome: progress in non-invasive prenatal diagnosis. Trends in Molecular Medicine 2003; 9:339-343.

Wagner et al. Non-invasive prenatal paternity testing from maternal blood. Int J Legal Med 2009; 123:75–79.

Zhong et al. Prenatal identification of fetal genetic traits. Lancet 2001; 357: 310-311.

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