The human homologue (PEG3) of the mouse paternally expressed gene 3 (Peg3) is maternally imprinted but not mutated in women with familial recurrent hydatidiform molar pregnancies
ABSTRACT We mapped a locus for autosomal recessive molar pregnancies with biparental genomic contribution to chromosome 19q13.4 between D19S924 and D19S890. This 5-Mb region is homologous to proximal mouse chromosome 7 and contains a cluster of Krüppel-type zinc finger genes, including the human homologue of the mouse imprinted genes: the paternally expressed gene 3 (PEG3) and the maternally expressed Zim1 genes. We analyzed the PEG3 gene for mutations in women with familial recurrent hydatidiform moles and to determine its imprinting status in humans.
We used database searches and screened cDNA libraries to find the complete genomic structure of PEG3. Polymerase chain reaction (PCR) amplification and direct sequencing of coding exons and flanking introns were performed on genomic DNA from the affected women. Allele-specific methylation and expression were studied by methylation-sensitive Southern analysis of a 5' located CpG island and by reverse-transcription PCR of total lymphoblast-derived RNA of normal individuals who were informative for two expressed polymorphisms.
We did not detect any mutations in the coding region of PEG3 in the affected women. We observed allele-specific methylation of the CpG island and expression from the paternal allele in two independent informative pedigrees.
Consistent with the findings in the mouse, the human PEG3 gene is expressed from the paternal allele. Our data support that PEG3 is not mutated in women with familial recurrent hydatidiform moles, although mutations in the regulatory regions that might affect imprinting or transcriptional level of the gene could not be evaluated.
SourceAvailable from: Heather E Wheeler
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ABSTRACT: Genetic (or 'genomic') imprinting, a feature of approximately 100 mammalian genes, results in monoallelic expression from one of the two parentally inherited chromosomes. To date, most studies have been directed on imprinted genes in murine or human models; however, there is burgeoning interest in the effects of imprinted genes in domestic livestock species. In particular, attention has focused on imprinted genes that influence foetal growth and development and that are associated with several economically important production traits in cattle, sheep and pigs. We have re-sequenced regions in 20 candidate bovine imprinted genes in order to validate single nucleotide polymorphisms (SNPs) that may influence important production traits in cattle. Putative SNPs detected via re-sequencing were subsequently re-formatted for high-throughput SNP genotyping in 185 cattle samples comprising 138 performance-tested European Bos taurus (all Limousin bulls), 29 African B. taurus and 18 Indian B. indicus samples. Analysis of the resulting genotypic data identified 117 validated SNPs. Preliminary genotype-phenotype association analyses using 83 SNPs that were polymorphic in the Limousin samples with minor allele frequencies ⩾0.05 revealed significant associations between two candidate bovine imprinted genes and a range of important beef production traits: average daily gain, average feed intake, live weight, feed conversion ratio, residual feed intake and residual gain. These genes were the Ras protein-specific guanine nucleotide releasing factor gene (RASGRF1) and the zinc finger, imprinted 2 gene (ZIM2). Despite the relatively small sample size used in these analyses, the observed associations with production traits are supported by the purported biological function of the RASGRF1 and ZIM2 gene products. These results support the hypothesis that imprinted genes contribute significantly to important complex production traits in cattle. Furthermore, these SNPs may be usefully incorporated into future marker-assisted and genomic selection breeding schemes.animal 12/2010; 4(12):1958-70. DOI:10.1017/S1751731110001163 · 1.78 Impact Factor
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ABSTRACT: Most genes are expressed from both parental chromosomes; however, a small number of genes in mammals are imprinted and expressed in a parent-of-origin specific manner. These imprinted genes play an important role in embryonic and extraembryonic growth and development, as well as in a variety of processes after birth. Many imprinted genes are clustered in the genome with the establishment and maintenance of imprinted gene expression governed by complex epigenetic mechanisms. Dysregulation of these epigenetic mechanisms as well as genomic mutations at imprinted gene clusters can lead to human disease.The International Journal of Developmental Biology 01/2014; 58(2-3-4):291-298. DOI:10.1387/ijdb.140077mb · 2.57 Impact Factor