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About 5% of the human genome consists of segmental duplications or low-copy repeats, which are large, highly homologous (>95%) fragments of sequence. It has been estimated that these segmental duplications emerged during the past ∼35 million years (Myr) of human evolution and that they correlate with chromosomal rearrangements. Williams-Beuren syndrome (WBS) is a segmental aneusomy syndrome that is the result of a frequent de novo deletion at 7q11.23, mediated by large (∼400-kb) region-specific complex segmental duplications composed of different blocks. We have precisely defined the structure of the segmental duplications on human 7q11.23 and characterized the copy number and structure of the orthologous regions in other primates (macaque, orangutan, gorilla, and chimpanzee). Our data indicate a recent origin and rapid evolution of the 7q11.23 segmental duplications, starting before the diversification of hominoids (∼12-16 million years ago [Mya]), with species-specific duplications and intrachromosomal rearrangements that lead to significant differences among those genomes. Alu sequences are located at most edges of the large hominoid-specific segmental duplications, suggesting that they might have facilitated evolutionary rearrangements. We propose a mechanistic model based on Alu-mediated duplicated transposition along with nonallelic homologous recombination for the generation and local expansion of the segmental duplications. The extraordinary rate of evolutionary turnover of this region, rich in segmental duplications, results in important genomic variation among hominoid species, which could be of functional relevance and predispose to disease.

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In human obesity, spontaneous and GRF stimulated growth hormone secretion have been shown to be blunted. We used cafeteria diet fed obese rats as a model to study the central mechanisms involved in growth hormone secretion changes which are observed in obesity. We analysed somatostatin messenger RNA and protein levels in the hypothalamic periventricular nucleus of the rats by non radioactive in situ hybridization and immunocytochemistry respectively. The optical density of somatostatin mRNA, measured by a computerized image system, was significantly higher in cafeteria diet fed rats (1014 +/- 87 vs 444 +/- 45; p < 0.05). The integrated optical density of somatostatin protein was also significantly higher in cafeteria rats compared to the control rats (222 +/- 36 vs 114 +/- 24; p < 0.05). In conclusion, cafeteria diet induced obese rats have a higher somatostatin biosynthesis in the periventricular nucleus. Further studies are needed to establish the possible link of this increased somatostatin gene expression with the decreased GH production.

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