Project/Area Number |
10672138
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human genetics
|
Research Institution | Ryukyu University (1999) Nagasaki University (1998) |
Principal Investigator |
JINNO Yoshihiro Ryukyu University, School of Medicine, Professor, 医学部, 教授 (20179097)
|
Co-Investigator(Kenkyū-buntansha) |
ISHIMARU Tadayuki Nagasaki University, School of Medicine, Professor, 医学部, 教授 (20039580)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | benign ovarian teratoma / genomic imprinting / methylation / H19 / SNRPN / HERV-K / 卵巣奇形腫 / 配偶子特異性 |
Research Abstract |
In humans, studies of female germ cells are very limited by ethics. The current study investigated the usefulness of benign ovarian teratomas as a substitute for ova in analyses of imprinted genes. Twenty-five human benign ovarian teratomas were typed with 45 microsatellite DNA markers and classified according to their genotypic features. Two oppositely imprinted genes, H19 and SNRPN, were then chosen for analysis of their methylation states in these tumors. These analyses revealed that benign ovarian teratomas consist of a mixture of genetically and epigenetically heterogeneous cell populations. In contrast to previous reports, we could document only one case rising from germ cells by meiosis-II nondisjunction. H19 and SNRPN were methylated in individual teratomas to various degrees, ranging from normal somatic cell to expected ovum levels. The allele with residual methylation of H19 was consistent with that methylated in the patient's blood DNA, thus being of paternal origin. Degrees of H19 hypomethylation and SNRPN hypermethylation increased as the cellular origin of the tumors advanced in oogenesis and were closely correlated in individual teratomas. These results could be best explained by the assumption that the primary imprinting is a progressively organized process and suggest that the establishment of primary imprints on different genes might be mechanistically linked, even when those genes are oppositely imprinted. Transcripts of six genes of human endogenous retrovirus K (HERV-K)-family members were detected by sequencing of RT-PCR clones in the placenta, testis, peripheral blood leukocytes and fetal lung. Three of them, which were expressed at least in the two tissues analysed, were isolated from a BAC library.
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