Constitutional DNA copy number changes in ICSI children
Authors: Woldringh, G.H.; Janssen, I.M.; Hehir-Kwa, J.Y.; van den Elzen, C.; Kremer, J.A.M.; de Boer, P.; Schoenmakers, E.F.P.M.
Source: Human Reproduction, Volume 24, Number 1, 23 January 2009 , pp. 233-240(8)
Publisher: Oxford University Press
Abstract:BACKGROUNDOver the last three decades, technological developments facilitating assisted reproductive techniques (ART) have revolutionized the treatment of subfertile couples, including men suffering from severe oligospermia or azoospermia. In parallel with the advent of these technologies, there is a great concern about the biological safety of ART. This concern is supported by the clinical observation that the frequency of congenital malformations is slightly elevated among ART-conceived children.METHODSIn this explorative study, we have used tiling-resolution BAC array-mediated comparative genomic hybridization to investigate the incidence of de novo genomic copy number changes in a group of 12 ICSI children, compared with a control group of 30 naturally conceived children.RESULTSIn 6 of the 12 ICSI children, we found 10 apparently de novo same direction genomic copy number changes [i.e. simultaneous copy number gain (or loss) with respect to both biological parents], notably losses. In statistically significant contrast, similar observations were encountered only six times in the control group in 5 of the 30 children. However, our study group was small, so a larger group is needed to confirm these findings.CONCLUSIONSLoci at which we found de novo alterations are known from the human genome database to be prone to large DNA segment copy number changes. As discussed, various molecular mechanisms, including the consequences of delayed male meiotic synapsis and replication fork stalling at early embryonic cell cycles, might trigger these copy number changes.
Document Type: Research article
Publication date: 2009-01-23
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.