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Sperm linked to ART-related genetic disorders

07 December 2009

By Dr Vivienne Raper

Appeared in BioNews 537

Mutations in sperm used for IVF and ICSI may be responsible for causing the rare genetic disorders potentially associated with these techniques.

Disorders like Beckwith-Wiedemann syndrome have increased among children born by assisted reproductive technologies (ART). Assisted conception techniques, such as in vitro culturing, have been blamed. A study published in the European Journal of Human Genetics has shown that, in some cases, the cause may be errors in the father's sperm associated with infertility.

Beckwith-Wiedemann syndrome is caused by errors in genetic imprinting- the activation or deactivation of genes during development dependent on which parent they come from. A process called DNA methylation is critical to imprinting. A team led by Dr Takahiro Arima from Tohoku University examined DNA methylation in 78 six to nine-week-old embryos and fetuses conceived using ART, and 38 conceived without ART. They also examined the father's sperm and DNA. In seven of 17 cases where there was abnormal DNA methylation in the ART sample, identical alterations were present in the father's sperm. The abnormal DNA methylation in the sperm was associated with variations in a gene coding for DNMT3L - a key enzyme in DNA methylation associated with abnormal imprinting and low sperm count.

In their paper, the team recommends that routine sperm screening during assisted conception should include imprint methylation analysis and that this could 'substantially reduce the likelihood of abnormal samples being used in ART'.

Using the analysis techniques, the team examined the methylation status of seven Autosoma imprinted genes (H19, GTL2, PEG1, KCNQ10T1, ZAC, PEG3 and SNRPN) and the XIST gene, which is linked to the X-chromosome. The methylation status of non-imprinted sequences of repeating DNA called Alu and LINE1 was also examined, and the team found no detectable differences between the ART and normal samples.

 

SOURCES & REFERENCES
European Journal of Human Genetics | 27 May 2009
 

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