{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T15:44:55Z","timestamp":1759160695080},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: A growing body of literature has demonstrated the potential for non-invasive diagnosis of a variety of human genetic diseases using cell-free DNA extracted from maternal plasma samples in early gestation. Such methods are of great significance to the obstetrics community because of their potential use as clinical standard of care. Proof of concept for such approaches has been established for aneuploidy and paternally inherited dominant traits. Although significant progress has recently been made, the non-invasive diagnosis of monogenic diseases that segregate in a recessive mendelian fashion is more problematic. Recent developments in microfluidic digital PCR and DNA sequencing have resulted in a number of recent advances in this field. These have largely, although not exclusively, been used for the development of diagnostic methods for aneuploidy. However, given their prevalence, it is likely that such methods will be utilized towards the development of non-invasive methods for diagnosing monogenetic disorders.<\/jats:p>\n               <jats:p>Results: With this in mind, we have undertaken a statistical modeling of three contemporary (digital) analytical methods in the context of prenatal diagnosis using cell free DNA for monogenic diseases that segregate in a recessive mendelian fashion. We provide an experimental framework for the future development of diagnostic methods in this context that should be considered when designing molecular assays that seek to establish proof of concept in this field.<\/jats:p>\n               <jats:p>Contact: \u00a0dgp6@pitt.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq544","type":"journal-article","created":{"date-parts":[[2010,9,25]],"date-time":"2010-09-25T00:18:28Z","timestamp":1285373908000},"page":"2863-2866","source":"Crossref","is-referenced-by-count":4,"title":["Statistical considerations for digital approaches to non-invasive fetal genotyping"],"prefix":"10.1093","volume":"26","author":[{"given":"Tianjiao","family":"Chu","sequence":"first","affiliation":[{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"},{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"}]},{"given":"Kimberly","family":"Bunce","sequence":"additional","affiliation":[{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"},{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"}]},{"given":"W. Allen","family":"Hogge","sequence":"additional","affiliation":[{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"},{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"}]},{"given":"David G.","family":"Peters","sequence":"additional","affiliation":[{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"},{"name":"1 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and 2Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA"}]}],"member":"286","published-online":{"date-parts":[[2010,9,23]]},"reference":[{"key":"2023012507551238200_B1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature07517","article-title":"Accurate whole human genome sequencing using reversible terminator chemistry","volume":"456","author":"Bentley","year":"2008","journal-title":"Nature"},{"key":"2023012507551238200_B2","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1373\/clinchem.2005.056937","article-title":"Fetal rhesus D mRNA is not detectable in maternal plasma","volume":"51","author":"Chiu","year":"2005","journal-title":"Clin. Chem."},{"key":"2023012507551238200_B3","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/clinchem\/47.9.1607","article-title":"Effects of blood-processing protocols on fetal and total DNA quantification in maternal plasma","volume":"47","author":"Chiu","year":"2001","journal-title":"Clin. Chem."},{"key":"2023012507551238200_B4","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1373\/clinchem.2009.136507","article-title":"Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21","volume":"56","author":"Chiu","year":"2010","journal-title":"Clin. Chem."},{"key":"2023012507551238200_B5","article-title":"Sampling, amplifying, and resampling","volume-title":"Technical Report 133","author":"Chu","year":"2002"},{"key":"2023012507551238200_B6","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1093\/bioinformatics\/btp156","article-title":"Statistical model for whole genome sequencing and its application to minimally invasive diagnosis of fetal genetic disease","volume":"25","author":"Chu","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012507551238200_B7","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/pd.2335","article-title":"A microarray-based approach for the identification of epigenetic biomarkers for the noninvasive diagnosis of fetal disease","volume":"29","author":"Chu","year":"2009","journal-title":"Prenat. Diagn."},{"key":"2023012507551238200_B8","doi-asserted-by":"crossref","first-page":"16266","DOI":"10.1073\/pnas.0808319105","article-title":"Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood","volume":"105","author":"Fan","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012507551238200_B9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1126\/science.1150427","article-title":"Single-molecule DNA sequencing of a viral genome","volume":"320","author":"Harris","year":"2008","journal-title":"Science"},{"key":"2023012507551238200_B10","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1001\/jama.293.7.843","article-title":"Detection of paternally inherited fetal point mutations for beta-thalassemia using size-fractionated cell-free DNA in maternal plasma","volume":"293","author":"Li","year":"2005","journal-title":"JAMA"},{"key":"2023012507551238200_B11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1196\/annals.1368.010","article-title":"Cell-free DNA in maternal plasma: is it all a question of size?","volume":"1075","author":"Li","year":"2006","journal-title":"Ann. N Y Acad. Sci."},{"key":"2023012507551238200_B12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/pd.1608","article-title":"Non-invasive prenatal detection of achondroplasia in size-fractionated cell-free DNA by MALDI-TOF MS assay","volume":"27","author":"Li","year":"2007","journal-title":"Prenat. Diagn."},{"key":"2023012507551238200_B13","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3109\/07853899908995896","article-title":"Fetal RhD genotyping from maternal plasma","volume":"31","author":"Lo","year":"1999","journal-title":"Ann. Med."},{"key":"2023012507551238200_B14","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1093\/clinchem\/46.12.1903","article-title":"Fetal DNA in maternal plasma: biology and diagnostic applications","volume":"46","author":"Lo","year":"2000","journal-title":"Clin. Chem."},{"key":"2023012507551238200_B15","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1471-0528.2008.02010.x","article-title":"Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art","volume":"116","author":"Lo","year":"2009","journal-title":"BJOG"},{"key":"2023012507551238200_B16","doi-asserted-by":"crossref","first-page":"13116","DOI":"10.1073\/pnas.0705765104","article-title":"Digital PCR for the molecular detection of fetal chromosomal aneuploidy","volume":"104","author":"Lo","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012507551238200_B17","doi-asserted-by":"crossref","first-page":"19920","DOI":"10.1073\/pnas.0810373105","article-title":"Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma","volume":"105","author":"Lun","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012507551238200_B18","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/pd.614","article-title":"Accuracy of trisomy 18 screening using the second-trimester triple test","volume":"23","author":"Meier","year":"2003","journal-title":"Prenat. Diagn."},{"key":"2023012507551238200_B19","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1093\/bioinformatics\/btn512","article-title":"Efficient mapping of applied biosystems SOLiD sequence data to a reference genome for functional genomic applications","volume":"24","author":"Ondov","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012507551238200_B20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/096914130301000302","article-title":"Maternal serum screening in Ontario using the triple marker test","volume":"10","author":"Summers","year":"2003","journal-title":"J. Med. Screen"},{"key":"2023012507551238200_B21","first-page":"1301","article-title":"The implications of a false positive second-trimester serum screen for Down syndrome","volume":"101","author":"Summers","year":"2003","journal-title":"Obstet. Gynecol."},{"key":"2023012507551238200_B22","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1373\/clinchem.2006.076851","article-title":"Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: theoretical and empirical considerations","volume":"52","author":"Tong","year":"2006","journal-title":"Clin. Chem."},{"key":"2023012507551238200_B23","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1136\/jmg.2003.016881","article-title":"Systematic micro-array based identification of placental mRNA in maternal plasma: towards non-invasive prenatal gene expression profiling","volume":"41","author":"Tsui","year":"2004","journal-title":"J. Med. Genet."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/22\/2863\/48851334\/bioinformatics_26_22_2863.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/22\/2863\/48851334\/bioinformatics_26_22_2863.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T07:55:42Z","timestamp":1674633342000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/26\/22\/2863\/227857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,23]]},"references-count":23,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2010,11,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btq544","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,11,15]]},"published":{"date-parts":[[2010,9,23]]}}}