Skip Navigation


Hum. Reprod. Advance Access originally published online on May 31, 2006
Human Reproduction 2006 21(8):2047-2051; doi:10.1093/humrep/del064
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF ) Freely available
Right arrow All Versions of this Article:
21/8/2047    most recent
del064v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Altarescu, G.
Right arrow Articles by Renbaum, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Altarescu, G.
Right arrow Articles by Renbaum, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Single-sperm analysis for haplotype construction of de-novo paternal mutations: application to PGD for neurofibromatosis type 1

G. Altarescu1, B. Brooks2, Y. Kaplan1, T. Eldar-Geva2, E.J. Margalioth2, E. Levy-Lahad1,3 and P. Renbaum1,4

1 Medical Genetics Unit 2 IVF Unit, Zohar PGD Laboratory Shaare Zedek Medical Center and 3 Hebrew University-Hadassah Medical School, Jerusalem, Israel

4 To whom correspondence should be addressed at: Medical Genetics Unit, Shaare Zedek Medical Center, Jerusalem 91031, Israel. E-mail: renbaum{at}szmc.org.il

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the neurofibromin gene. Approximately, 50% of cases are caused by de-novo mutations. Even when the NF1 mutation is known, accuracy of PGD is highly enhanced by simultaneous analysis of linked markers. In a childless couple referred to PGD, the male carried a de-novo mutation, precluding the possibility of typing relatives to establish the mutation-associated haplotype. We developed a single-sperm haplotype analysis strategy to establish the haplotype linked to the NF1 mutation. METHODS: Spermatozoa from freshly ejaculated semen were used as a substrate for multiplex PCR on single sperm. RESULTS: In addition to the NF1 mutation, six informative polymorphic markers flanking the NF1 gene (D17S1294, D17S1849, D17S841, D17S975, NF1TG2 and NF1AC5) were linked to individual alleles in single sperm from the affected male. CONCLUSIONS: Single-sperm analysis established the haplotypes of both mutant and wild-type NF1 alleles and enabled the implementation of a PGD protocol using polymorphic marker analysis. This method is generally applicable to PGD for any disease in which the haplotype of paternal mutations cannot be determined by typing relatives.

Key words: single-sperm PCR/NF1/PGD/polymorphic markers


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum ReprodHome page
G. Altarescu, T. Eldar-Geva, I. Varshower, B. Brooks, E. Z. Haran, E. J. Margalioth, E. Levy-Lahad, and P. Renbaum
Real-time reverse linkage using polar body analysis for preimplantation genetic diagnosis in female carriers of de novo mutations
Hum. Reprod., August 17, 2009; (2009) dep293v1.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.