Detection of single-copy fetal DNA sequence from maternal blood

Lo, Yen-Li; Patel, P.; Sampietro, Maurizio; Gillmer, M. D. G.; Fleming, K. A.; Wainscoat, J S

doi:10.1016/0140-6736(90)91491-r

Cited by 146 publications

(80 citation statements)

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“…In 1989, Lo et al 4 were the first to show that the Y chromosome-specific sequences from a male fetus could be amplified from blood samples of pregnant women by PCR. This report was soon followed by several additional reports that confirmed this finding and documented the existence of fetus-derived genetic material, 5 trophoblasts, 6 and nucleated erythrocytes 7 in the peripheral blood of pregnant women. In these studies, the Y chromosome sequences were detected as early as 15 to 16 weeks 7 or 9 weeks, 6 and even as early as 6 weeks of gestation.…”

Section: Detection Of Fetal Microchimerismmentioning

confidence: 51%

“…In these studies, the Y chromosome sequences were detected as early as 15 to 16 weeks 7 or 9 weeks, 6 and even as early as 6 weeks of gestation. 5 In 1994, Thomas et al 8 took advantage of the availability of serial blood samples from women who became pregnant through in vitro fertilization to address the question of when fetal-cell DNA would first appear in the peripheral blood of pregnant women. They showed that the Y chromosomal sequences from male fetuses were detectable in the maternal blood as early as gestational ages of 4 weeks 5 days and 5 weeks 5 days.…”

Section: Detection Of Fetal Microchimerismmentioning

confidence: 99%

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Fetal microchimerisms in the mother: Immunologic implications

et al. 2000

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The previously held concept that the fetus is completely separated from the mother, especially by trophoblasts that line the outer layer of the placenta, has recently been questioned. It has recently been shown that fetal cells are detectable not only in the peripheral blood, but also in maternal skin and liver. Although the migration of fetal cells into the maternal circulation has been given a great deal of attention because of its implication in the prenatal diagnosis of genetic diseases, the potential role of such placental transfer of fetal cells in the pathogenesis of autoimmune diseases has only recently been considered. In patients with scleroderma, fetal cell-derived DNA was detected more frequently in the peripheral blood of patients than controls. This finding of a limited number of fetal cells in maternal tissues leading to microchimerism has been proposed to have a role in the induction of scleroderma. Although evidence for microchimerism has also been confirmed in a high frequency of liver tissues from patients with primary biliary cirrhosis (PBC), a similar high frequency was noted in control patients, which suggests that microchimerism by itself is unlikely to fully account for the pathogenesis of PBC. The finding of such a high frequency of fetal microchimerism in the liver suggests that this is a very common event, raising the possibility that the migration of fetal cells may be important in the induction and subsequent maintenance of tolerance against the fetus during pregnancy. In addition, it is clearly possible that such microchimerism could contribute to the pathogenesis of select autoimmune diseases. Copyright 2000 by the American Association for the Study of Liver DiseasesA lthough the fetus in the uterus is sequestered from the mother by the placenta, this is not a mechanically complete barrier. Several examples show that fetal cells migrating into the maternal body can be found in such tissues as blood and skin. Fetal-derived DNA can be detected in maternal peripheral blood at early stages of gestation and persist long after pregnancy. Recently, our laboratory has also shown that fetal cell-derived genes are detectable in maternal liver tissue, in some cases as long as 43 years after pregnancy. Whether this microchimerism, i.e., migration and presence of fetal cells within maternal tissues, has an important role in either physiological or immunologic function is unclear, but the very high detection rate of fetal-derived DNA in the mother provides suggestive evidence that microchimerism may not be an uninvolved bystander. We review recent studies showing microchimerism in the mother and address its putative role in autoimmunity and the maintenance of tolerance against the fetus.

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Section: Detection Of Fetal Microchimerismmentioning

confidence: 51%

Section: Detection Of Fetal Microchimerismmentioning

confidence: 99%

Fetal microchimerisms in the mother: Immunologic implications

et al. 2000

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“…In the interval between the first and second phases of the study, we became aware of the application of nested PCR to the detection of rare cells (7). This technique has the advantage of suppressing nonspecific background amplification, permitting detection of rare cell populations without requiring Southern transfer and hybridization to detect a PCR product.…”

Section: Methodsmentioning

confidence: 99%

“…During this decade, investigators using PCR amplification of Y chromosome-specific sequences to identify fetal cells in maternal blood noted "false positive" results-i.e., detection of male DNA when the fetus was female (6,7). Although laboratory contamination as a source of true false positives can be a concern (8), it appears that, in some cases, the male DNA was a real finding, possibly originating from a prior pregnancy (9).…”

mentioning

confidence: 99%

Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum

1996

Transfusion Medicine Reviews

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Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. pearance. In a group of 20 primigravidas sampled on more than one occasion postpartum, quinacrine fluorescent signals ("Y body") were seen at a frequency of 0.01-0.1% of lymphocytes. These frequencies were noted to remain "practically unchanged" up until 1 year after delivery, when the study ended. In a related study, Ciaranfi et al. (5) (4) to include samples from women 5-7 years postpartum (5). In a series of 62 women who delivered a male infant, more than half had detectable male lymphocytes 2 years after birth. In some cases, metaphases with a Y chromosome were visualized 5 years postpartum. These studies, although intriguing, were performed in the 1970s using techniques less sensitive and less accurate than those available today.During this decade, investigators using PCR amplification of Y chromosome-specific sequences to identify fetal cells in maternal blood noted "false positive" results-i.e., detection of male DNA when the fetus was female (6, 7). Although laboratory contamination as a source of true false positives can be a concern (8), it appears that, in some cases, the male DNA was a real finding, possibly originating from a prior pregnancy (9). Other investigators studied postpartum maternal samples without using cell separation techniques to enrich for specific subpopulations of fetal cells and concluded that fetal cells did not persist postpartum (10).The study reported here occurred in two parts. Initially, we used a monoclonal antibody to cluster differentiation antigen (CD) 34 to isolate fetal hematopoietic stem cells from the blood of pregnant women. The surprising results, described below, suggested that the gender of the circulating CD34+ cells did not always correlate with the fetal gender of the current pregnancy. This led to the hypothesis that fetal CD34+ cells could persist from a prior pregnancy. We tested this hypothesis by fluorescence-activated cell sorting of four specific subpopulations of mononuclear cells from women who were not presently pregnant but who had previously given birth to a male infant. Although we were in...

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“…Molecular biological techniques have shown that fetal cells can be detected in maternal peripheral blood in most pregnancies [1][2][3] . On this observation, the radical hypothesis of autoimmune disease, proposed in 1996, may be caused by fetal cells that are retained after pregnancies [4] .…”

Section: Introductionmentioning

confidence: 99%

Lack of evidence for leukocyte maternal microchimerism in primary biliary cirrhosis

Nomura

Sumida²,

Yoh³

et al. 2004

WJG

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AIM:It is reasonable to assume that microchimerism could also be involved in the induction of primary biliary cirrhosis (PBC). However, previous reports investigated only fetus-microchimerism in women patients. Maternal microchimerism has not been investigated until now. The current study aimed to clear either maternal microchimerism was involved in the pathogenesis of PBC or not. METHODS:We used fluorescence in situ hybridization on paraffin-embedded tissue (We called "Tissue-FISH".) to determine whether maternal cells infiltrated in male patients who were diagnosed as having PBC. Tissue-FISH was performed by using both X and Y specific probes on the biopsy liver sample of 3 male PBC patients. RESULTS:Infiltrating lymphocytes demonstrated both X and Y signals in all 3 male patients. CONCLUSION:Maternal microchimerism dose not play a significant role in PBC. PBC may not relate to fetus and maternal microchimerism.

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Detection of single-copy fetal DNA sequence from maternal blood

Cited by 146 publications

References 2 publications

Fetal microchimerisms in the mother: Immunologic implications

Fetal microchimerisms in the mother: Immunologic implications

Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum

Lack of evidence for leukocyte maternal microchimerism in primary biliary cirrhosis

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