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To identify the mechanism of loss of heterozygosity (LOH) and potential modifier gene(s), we investigated the molecular basis of somatic NF1inactivation in myeloid malignancies from 10 children with neurofibromatosis type 1. Loci across a minimal 50-Mb region of primarily the long arm of chromosome 17 showed LOH in 8 cases, whereas a less than 9-Mb region of loci flanking NF1had LOH in the remaining 2 cases. Two complementary techniques, quantitative polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), were used to determine whether the copy number at loci that showed LOH was 1 or 2 (ie, deleted or isodisomic). The 2 cases with LOH limited to less than 9 Mb were intrachromosomal deletions. Among the 8 leukemias with 50-Mb LOH segments, 4 had partial uniparental isodisomy and 4 had interstitial uniparental isodisomy. These isodisomic cases showed clustering of the centromeric and telomeric LOH breakpoints. This suggests that the cases with interstitial uniparental isodisomy arose in a leukemia-initiating cell by double-homologous recombination events at intervals of preferred mitotic recombination. Homozygous inactivation of NF1favored outgrowth of the leukemia-initiating cell. Our studies demonstrate that LOH analyses of loci distributed along the chromosomal length along with copy-number analysis can reveal novel mechanisms of LOH that may potentially identify regions harboring “cryptic” tumor suppressor or modifier genes whose inactivation contributes to tumorigenesis.

The abundance of the transposable elementmarinerdiffers dramatically in the genomes of the closely related speciesDrosophila simulans, D. mauritiana, D. sechellia, andD. melanogaster. Natural populations ofD. simulansandD. mauritianahave 1–10 and 20–30 copies per diploid genome, respectively, and the insertion sites are polymorphic. The element has not been found inD. melanogaster. In this paper we show thatD. sechellia, a species endemic to the Seychelles Islands, contains only twomarinerelements that are at fixed sites in the genome. One element, inserted in chromosome 2R at 51A1–2, contains three deletions and is missing much of the 3′ end. The other element, inserted in chromosome 3L at 64A10–11, is the full length of 1286 bp. Although the sequence of the full-length element is polymorphic in populations ofD. sechellia, at least some of the sequences are closely related to elements fromD. simulansandD. mauritianathat are known to be active. However, judging from the progeny of crosses betweenD. sechelliaandD. simulans, the biological activity of the full-lengthD. sechelliaelement appears to be low, either because of the nucleotide sequence of the element or because of its position in the genome, or both.

In studies on the biogenesis of vasocontrictive macrolides, zooxanthellatoxins isolated from a symbiotic dinoflagellate Symbiodiniumsp., we have investigated metabolites of the dinoflagellate cultured under different conditions. Four new compounds were isolated from 70% EtOH extract of the cells cultured in f/2 medium. Two betaines (zooxanthellabetaine-A and -B) were obtained from a neutral fraction of n-BuOH soluble portion and the structure of zooxanthellabetaine-A was determined as 4-(4-hydroxybenzoyloxy)-3-(trimethylammonio)butyrate. The EtOAc soluble portion afforded a new C-30 alkaloid, zooxanthellamine, and a new ceramide, symbioramide-C16. The structural similarity of zooxanthellamine to zoanthid alkaloids, zoanthamines, suggested an algal origin of these zoanthamines. Zooxanthellamine might be derived biogenetically from a polyketide chain presumably started from a glycine unit, like other marine toxins such as zooxanthellatoxin and palytoxin.