No abstract

The study of family members underlines the variable expression of NC-CAH even within a family, suggesting that modifier factors may modulate phenotype expression. Post-ACTH 21dF cannot reliably detect heterozygous subjects. Considering the high frequency of heterozygotes in the general population, it is essential to genotype the partner(s) of the patients with one severe mutation to offer genetic counseling.

Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin's structural dynamics and evolution. Here, we focus on a 180-kb heterochromatic locus producing Piwi-interacting RNAs (piRNA cluster), the flamenco (flam) locus, known to be responsible for the control of at least three transposable elements (TEs). We report its detailed structure in three different Drosophila lines chosen according to their capacity to repress or not to repress the expression of two retrotransposons named ZAM and Idefix, and we show that they display high structural diversity. Numerous rearrangements due to homologous and nonhomologous recombination, deletions and segmental duplications, and loss and gain of TEs are diverse sources of active genomic variation at this locus. Notably, we evidence a correlation between the presence of ZAM and Idefix in this piRNA cluster and their silencing. They are absent from flam in the strain where they are derepressed. We show that, unexpectedly, more than half of the flam locus results from recent TE insertions and that most of the elements concerned are prone to horizontal transfer between species of the melanogaster subgroup. We build a model showing how such high and constant dynamics of a piRNA master locus open the way to continual emergence of new patterns of piRNA biogenesis leading to changes in the level of transposition control.RNAi | gene silencing | epigenetics O ver the course of evolution, transposable elements (TEs) have accumulated in the genomes of eukaryotes, where they can account for up to 85% of the DNA (1). Most of these sequences have lost their ability to transpose. They are now stable components of the genomes. Their conservation throughout evolution suggests that they may confer advantageous effects to their hosts. However, transposition of the copies that remain functional could generate deleterious mutations if they were not severely repressed by their host. RNAi, which is a gene-silencing mechanism triggered by small RNAs (reviewed in ref.2), has been identified as being the main cellular machinery involved in the "taming" of TEs (reviewed in refs. 3-5). RNAi pathways involve small RNAs of diverse families. Among them, Piwiinteracting RNAs (piRNAs) have been shown to be involved in TE silencing in the Drosophila ovary. These piRNAs, 23-29 nt long, are bound by the Argonaute proteins Piwi, Argonaute 3, or Aubergine. They are produced by discrete genomic loci named piRNA clusters, which have been described as containing vestiges of TEs (6). One of these loci, the flamenco (flam) locus, extends over 180 kilobases (kb) on the Drosophila X chromosome. It is proximal to the DISCO interacting protein 1 gene (DIP1) and close to pericentromeric heterochromatin. Before the identification of piRNAs, this locus had been shown to regulate the Gypsy retrotransposon (7, 8 (6) showed the potential for the flam cluster to pr...