The solitary long terminal repeats (LTRs) of ERV-9 endogenous retrovirus contain the U3, R, and U5 regions but no internal viral genes. They are middle repetitive DNAs present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of the 5 boundary area of the erythroid ␤-globin locus control region (␤-LCR) and the intron of the embryonic axin gene show that a solitary ERV-9 LTR has been stably integrated in the respective loci for at least 15 million years in the higher primates from orangutan to human. The solitary long terminal repeats (LTRs) of human endogenous retroviruses comprise approximately 5% of the human genome and belong to the category of middle repetitive DNAs characterized as retrotransposons (14,19,24,35). These solitary LTRs contain the U3 enhancer and promoter region, the transcribed R region whose 5Ј end marks the initiation site of retroviral RNA synthesis, and the U5 region (27) but no internal gag, pol, and env genes. During primate evolution, the LTRs were apparently self-replicated and inserted into various host chromosomal sites. The functional roles in the host genomes of these transposed, repetitive DNAs are not clear. The LTR retrotransposons have been suggested to be selfish DNAs that do not serve relevant host functions (8). However, recent findings indicate that the solo LTRs can provide enhancers and promoters for cis-linked genes and regulate host gene transcription (9,10,22,25,26,29).The human genome contains approximately 50 copies of the ERV-9 endogenous retrovirus and an additional 3,000 to 4,000 copies of solitary ERV-9 LTRs (15,17,19,35,36). Compared with the LTRs of other families of endogenous retroviruses, the ERV-9 LTRs exhibit an unusual sequence feature: the U3 regions contain from 5 to 17 tandem repeats of 37 to 41 bases (17, 18) with recurrent GATA (23), CCAAT (28), and CCACC (21) motifs potentially capable of binding to cognate transcription factors expressed in embryonic and hematopoietic cells.This suggests that the ERV-9 enhancer and promoter could be active in those cells.To gain further insight into the stability and functional significance of the ERV-9 LTRs, here we have mapped the erythroid ␤-globin and embryonic axin gene loci in primates by using human primers in PCR. We found a solitary ERV-9 LTR that is conserved in identical locations in the 5Ј boundary area of the ␤-globin gene locus and in the axin gene in the higher primates orangutan, gorilla, chimpanzee, and human, whose ancestors diverged over an evolutionary period of 15 million years (12). In the lower primates gibbon and monkey, whose ancestors diverged from the human ancestor 18 and 25 million years ago, respectively (12), the globin and axin LTRs are absent in the respective gene loci. However, other ERV-9 LTRs are detectable in the monkey genome. These results indicate that copies of the ERV-9 LTRs present in the lower primates were inserted into the globin and axin gene loci in the common ancestor of the higher primates 15 to 18 millions years ago and have remained stably integrate...

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Multiple displacement amplification (MDA) renders an increased quantity of genomic DNA available for comparative genomic hybridization (CGH), enabling it to be used to identify genomic imbalances in human blastomeres. The karyotypic lineage of 57 blastocysts derived from 11 ovum donors following ovarian stimulation was examined. CGH was performed on all first polar bodies, and linearly on corresponding second polar bodies and blastomeres. A diploid karyotype was propagated from the prefertilized oocyte to the embryo in 25 (44%) sets of analyses. In 32/57 sets (56%), aneuploidy was detected in the post-fertilized zygotes/embryos and in nine (28%) of such cases the aneuploidy was 'chaotic' (> or =3 chromosomes). In 4/57 cases (7%) mitotic aneuploidy was observed. CGH and fluorescence in-situ hybridization (FISH) were concurrently performed on two blastomeres removed from each of 44 embryos obtained from four patients. In 43 (98%) of these embryos there was a direct karyotypic correlation between nine-probe commercial FISH and CGH. CGH identified > or =15% more chromosomal abnormalities than through FISH alone. The linear propagation using MDA-CGH, of the same karyotypic abnormalities that affected the oocyte of origin, in the corresponding embryos, coupled with the fact that CGH confirmed the aneuploidies identified through FISH, validates the accuracy and reliability of CGH technology.