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Inferring The Origins Of Cord Blood Cell-Free DNA Using Tissue-Specific Methylation Patterns: A Window Into Perinatal Tissue Dynamic
Home ‹ 2010 Abstracts ‹ Inferring The Origins Of Cord Blood Cell-Free DNA Using Tissue-Specific Methylation Patterns: A Window Into Perinatal Tissue Dynamic

Ori Fridlich1, Agnes Klochendler1, Sorina Grisaru-Granovsky2, Shai Porat3, Noa Ofek Shlomai4 Benjamin Glaser5, Ruth Shemer1, Yuval Dor1

1Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem.

2Division of Maternal Fetal Medicine, Shaare Zedek Medical Center Jerusalem

3Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center.

4Department of Neonatology, Hadassah-Hebrew University Medical Center, Jerusalem.

5Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem

Introduction: Dying cells release small fragments of DNA into the bloodstream. This cell-free circulating DNA (cfDNA) is emerging as a powerful biomarker in various areas such as prenatal diagnosis. Tools that can identify the source tissue of cfDNA could be instrumental for studying development dynamics and for identifying and locating disease.

Methods: We have developed an approach to identify the tissues origins of cfDNA, based on tissue-specific methylation patterns that are retained in circulating DNA fragments. The method allows us to infer the turnover of specific human tissues. Here we apply this method to study the tissue origins of cfDNA derived from newborn cord blood plasma, as compared to adult plasma.

Results: We examined the presence of tissue specific cfDNA in cord blood from ~60 healthy, term babies, and identified cfDNA derived, for example: from placenta (up to 2,000 copies/ml), brain (up to 300 copies/ml), colon (up to 200 copies/ml), liver (up to 600 ng/ml), lung (up to 450 ng/ml) and beta cells (up to 50 copies/ml). Plasma of healthy adult donors was negative for all these markers.

Conclusion: The tissue origins of cfDNA found in cord blood plasma reflect cell turnover patterns during normal late embryonic development. Further assay development and a comparison to other fetal body fluids may provide insights into normal and pathological human fetal development.

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