| Research Abstract |
Identification of Silver-Russell syndrome (SRS) responsible region and candidate gene analysis : Allelotype analysis of one SRS patient with abnormal karyotype using microsatellite markers revealed that a 7p13-q11 segment showed biallelism while the remaining region of chromosome 7 showed only maternal alleles. The results indicated that the putative SRS region is confined to 7q11-qter. Although two genes on chromosohie 7, GRB10 and MEST, have become a candidate gene for SRS, results of an imprinting analysis of the gents using hybrid cell panels and methylation analysis did not support the hypothesis.
Construction of a 1.2-Mb PAC contig (physical and transcription map) : To confirm an imprinted gene cluster on 7q32, such a contig between D7S530 wAD7S649 including MEST was constructed. It contains 70 novel STSs, 9 novel genes, and 6 known genes.
Identification of imprinted genes at 7q32 : Among the genes mapped at the contig, the gene^ to be or not to be imprinted included MEST, COPG2, COPG2TT1 (CfTl), KIAA0265, CPA3, CPA1, mdTSGA14. Both MEST and COPG2IT1 are paternally expressed, while CPA3 is maternally expressed Although COPG2 was thought to be paternally expressed, it is actually biallelically expressed. However, a novel EST (COPG2IT1), the antisense transcript from COPG2-intron 20, showed paternally monoallelic expression in fetal tissues. CPA3 showed partially imprinted in the fetal heart, kidney and lung, and the adult prostate, whereas it loses imprinting partially or completely in lymphoblastoid cells. The findings that COPG2, KIAA 0265, CPA 1 and TSGA14 all showed biallelic expression did not support that their imprinting. These findings, especially the absence of imprinting of COPG2 and TSGA14 which are located nearby MEST suggest that the 7q32 region is not strictly controlled as an imprinting domain but controlled by independent imprinting signals.
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