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Israel Fertility Association (Ayala)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prenatal genetic testing is not generally applicable to the very early stages of pregnancy (prior to week 8 gestation), a time period that is crucial to pregnant couples with high risk for transmission of genetic disease to their fetus. Therefore, we developed a new ultra-sensitive targeted next generation sequencing method for noninvasive haplotype-based paternal allele exclusion testing of the cystic fibrosis-associated gene, <jats:italic>CFTR<\/jats:italic>. This new method was compared to a conventional library prep and sequencing analysis method and all test results were validated by amniotic fluid testing at later stages of pregnancy. Out of 7 enrolled couples, who provided at least two blood samples (at least one week apart) for noninvasive <jats:italic>CFTR<\/jats:italic> testing, a result was obtained for 6 fetuses. Using the new hypersensitive method, all six couples (100%) received a correct diagnosis for the paternal allele as opposed to 3\/6 (50%) when tested with the conventional strategy. Among 4 couples who provided just one early pregnancy blood draw for analysis, diagnosis was possible in one fetus, but only using the ultra-sensitive method. Thus, we describe a novel noninvasive <jats:italic>CFTR<\/jats:italic> screening method which demonstrates unprecedented fetal allele typing accuracy in the earliest stages of pregnancy.<\/jats:p>","DOI":"10.1038\/s41598-018-34396-6","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T10:33:00Z","timestamp":1540290780000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Noninvasive paternal exclusion testing for cystic fibrosis in the first five to eight weeks of gestation"],"prefix":"10.1038","volume":"8","author":[{"given":"David A.","family":"Zeevi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fouad","family":"Zahdeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yehuda","family":"Kling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzvia","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Renbaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Ron-El","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talia","family":"Eldar-Geva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hananel E. G.","family":"Holzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ephrat","family":"Levy-Lahad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gheona","family":"Altarescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,10,29]]},"reference":[{"key":"34396_CR1","doi-asserted-by":"publisher","unstructured":"Alfirevic, Z., Mujezinovic, F. & Sundberg, K. Amniocentesis and chorionic villus sampling for prenatal diagnosis. The Cochrane database of systematic reviews, CD003252\u2013CD003252, https:\/\/doi.org\/10.1002\/14651858.cd003252 (2003).","DOI":"10.1002\/14651858.cd003252"},{"key":"34396_CR2","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/humupd\/dmn047","volume":"15","author":"CF Wright","year":"2009","unstructured":"Wright, C. F. & Burton, H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Human reproduction update 15, 139\u2013151, https:\/\/doi.org\/10.1093\/humupd\/dmn047 (2009).","journal-title":"Human reproduction update"},{"key":"34396_CR3","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.siny.2010.10.003","volume":"16","author":"RW Chiu","year":"2011","unstructured":"Chiu, R. W. & Lo, Y. M. Non-invasive prenatal diagnosis by fetal nucleic acid analysis in maternal plasma: the coming of age. Seminars in fetal & neonatal medicine 16, 88\u201393, https:\/\/doi.org\/10.1016\/j.siny.2010.10.003 (2011).","journal-title":"Seminars in fetal & neonatal medicine"},{"key":"34396_CR4","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2147\/ijwh.s67124","volume":"7","author":"M Allyse","year":"2015","unstructured":"Allyse, M. et al. Non-invasive prenatal testing: a review of international implementation and challenges. International Journal of Women\u2019s Health 7, 113\u2013126, https:\/\/doi.org\/10.2147\/ijwh.s67124 (2015).","journal-title":"International Journal of Women\u2019s Health"},{"issue":"1","key":"34396_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000271995","volume":"27","author":"Ann Tabor","year":"2010","unstructured":"Tabor, A. & Alfirevic, Z. Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther 27, 1\u20137, 000271995 [pii]https:\/\/doi.org\/10.1159\/000271995 (2010).","journal-title":"Fetal Diagnosis and Therapy"},{"key":"34396_CR6","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.jogc.2016.01.002","volume":"38","author":"D Costescu","year":"2016","unstructured":"Costescu, D. et al. Medical Abortion. 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Otherwise, all other authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15941"}}