I THE CONCEPT OF HETEROCHROMATIN Definition of Chromatin In prokaryotes such as Escherichia coli there is no detectable heterochromatin, for the simple reason that there is no chromatin. The hereditary message is carried by a circular molecule of naked DNA, and there is no separate nuclear compartment. In eukaryotes, however, the DNA is packaged in the form of a nucleoprotein complex called "chromatin". The hereditary message is, therefore, carried by the chromatin. It is located in a nucleus and is organised in several separate entities, the chromosomes. The Concept of Heterochromatin The concept of heterochromatin, as described by Emil HEITZ in 1928, was exclusively based on histological observations. He defined heterochromatin (HC) as being the chromosomal segments which appear extremely condensed and dark in colour in the interphase nucleus. The rest of the nucleus is occupied by euchromatin, or true chromatin, which appears diffuse and relatively light in colour. Heitz's observations highlighted the fact that, in the interphase nucleus, chromatin does not have a homogeneous appearance. Electron microscopy and X-ray diffraction have since confirmed the heterogeneous structure of chromatin: it consists of a tangle of fibres, the diameter of which not only vary during the cell cycle, but also depend on the region of the chromosome observed. Euchromatin, in its active form, consists of a fibre with a diameter not exceeding 10-11nm. Its diameter corresponds to that of a nucleosome, which contains a 146 base pair double strand DNA segment, wound around 4 homodimers of the histones H2A, H2B, H3, and H4 . The inactive euchromatin is enriched in linker histone H1. Histone H1 binds two consecutive nucleosomes, which causes the 10-11nm fibre to wind itself into a solenoid with a 30nm diameter. The 30nm fibre is further organised through interactions with non-histone proteins which fold the chromatin fibre in loops around an imaginary axis. These proteins include topoisomerase II, which is located, in particular, at the base of the loops, the scaffold protein 2 and lamins, in addition to other proteins. At this stage, the diameter of the chromatin fibre attains approximately 200nm. As regards the heterochromatin, as defined above, its constituent fibre is more condensed and often appears to be composed of aggregates. It involves numerous additional proteins, including the HP1 proteins (Heterochromatin Protein 1).

N This is the largest series of patients to have been molecularly characterised and includes the r( 22) patient with the smallest deletion described to date.The minimum critical region responsible for the monosomy 22q13 phenotype includes the genes PROSAP2/SHANK3, ACR, and RABL2B, but not ARSA.

Using fluorescent in-situ hybridization, we investigated the positioning of different human bivalents at the pachytene stage of normal male meiosis. We showed that, in about 35% of nuclei, the pericentromeric region of bivalent 15 is closely associated with the sex vesicle (SV). This behaviour may be linked to the presence of three domains in the pericentromeric region of chromosome 15: a large imprinted domain, a nucleolar organizing region (NOR), and a heterochromatic block. In order to define the domains of chromosome 15 involved in this association, we analysed the meiotic behaviour of other bivalents with similar domains: human bivalent 11 and mouse bivalent 7, bearing imprinted domains, other human acrocentric bivalents bearing a NOR, and the human bivalents 1, 9 and 16 containing a heterochromatic region. None of these bivalents were as frequently associated with the SV as the human bivalent 15. Nevertheless, we suggest that the bivalent 15 heterochromatin may be responsible for the association because of two properties: its telomeric location on chromosome 15 and its strong sequence homology with the Yq heterochromatin. This phenomenon could explain the high frequency of translocations between the chromosome 15 and the X or Y chromosomes.

A new case of partial trisomy 13 through unbalanced de novo translocation t(X;13) is reported. In situ hybridization has been used to specify breakage points on the X chromosome. This case is cytogenetically comparable with another reported case; the phenotypical aspect of these two patients is however different. This discrepancy is discussed.