Chromosome-wide identification of novel imprinted genes using microarrays and uniparental disomies.
Genomic imprinting refers to a specialized form of epigenetic gene regulation whereby the expression of a given allele is dictated by parental origin. Defining the extent and distribution of imprinting across genomes will be crucial for understanding the roles played by imprinting in normal mammalian growth and development. Using mice carrying uniparental disomies or duplications, microarray screening and stringent bioinformatics, we have developed the first large-scale tissue-specific screen for imprinted gene detection. We quantify the stringency of our methodology and relate it to previous non-tissue-specific large-scale studies. We report the identification in mouse of four brain-specific novel paternally expressed transcripts and an additional three genes that show maternal expression in the placenta. The regions of conserved linkage in the human genome are associated with the Prader-Willi Syndrome (PWS) and Beckwith-Wiedemann Syndrome (BWS) where imprinting is known to be a contributing factor. We conclude that large-scale systematic analyses of this genre are necessary for the full impact of genomic imprinting on mammalian gene expression and phenotype to be elucidated.
Schulz
Reiner
R
King's College London, School of Medicine at Guy's, King's College and St. Thomas' Hospitals, Department of Medical and Molecular Genetics, 8th Floor Guy's Tower, London SE1 9RT, UK.
Menheniott
Trevelyan R
TR
Woodfine
Kathryn
K
Wood
Andrew J
AJ
Choi
Jonathan D
JD
Oakey
Rebecca J
RJ
D000818:Animals; D001921:Brain / Q000378:metabolism; D033481:Chromosomes, Mammalian; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling / Q000379:methods*; D018392:Genomic Imprinting; D023281:Genomics / Q000379:methods; D006801:Humans; D051379:Mice; D015341:Nucleic Acid Probes; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010920:Placenta / Q000378:metabolism; D024182:Uniparental Disomy
D015341:Nucleic Acid Probes