Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline

BMC Genetics

DT Bonthron²  E Sheridan²  H M Picton¹  J Huntriss¹  D Hodge³  H Judson³  M De Vos³  B E Hayward³ 

[1] Academic Unit of Paediatrics, Obstetrics and Gynaecology, University of Leeds, Leeds LS2 9NS, U.K;Yorkshire Regional Clinical Genetics Service, St. James's University Hospital, Leeds LS9 7TF, U.K;Molecular Medicine Unit, University of Leeds, Leeds LS9 7TF, U.K

关键词: oogenesis;    imprinting;    hydatidiform mole;    autozygosity;   

Others  :  1144068
DOI  :  10.1186/1471-2156-4-2

 received in 2002-12-03, accepted in 2003-01-20,  发布年份 2003

【 摘 要 】

Background

Differential methylation of the two alleles is a hallmark of imprinted genes. Correspondingly, loss of DNA methyltransferase function results in aberrant imprinting and abnormal post-fertilization development. In the mouse, mutations of the oocyte-specific isoform of the DNA methyltransferase Dnmt1 (Dnmt1o) and of the methyltransferase-like Dnmt3L gene result in specific failures of imprint establishment or maintenance, at multiple loci. We have previously shown in humans that an analogous inherited failure to establish imprinting at multiple loci in the female germline underlies a rare phenotype of recurrent hydatidiform mole.

Results

We have identified a human homologue of the murine Dnmt1o and assessed its pattern of expression. Human DNMT1o mRNA is detectable in mature oocytes and early fertilized embryos but not in any somatic tissues analysed. The somatic isoform of DNMT1 mRNA, in contrast, is not detectable in human oocytes. In the previously-described family with multi-locus imprinting failure, mutation of DNMT1o and of the other known members of this gene family has been excluded.

Conclusions

Mutation of the known DNMT genes does not underlie familial hydatidiform mole, at least in the family under study. This suggests that trans-acting factors other than the known methyltransferases are required for imprint establishment in humans, a concept that has indirect support from recent biochemical studies of DNMT3L.

【 授权许可】

   
2003 Hayward et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

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