Structural basis for Robertsonian translocations in man: association of ribosomal genes in the nucleolar fibrillar center in meiotic spermatocytes and oocytes.

Abstract

The spatial relationships of acrocentric chromosomes were studied during prophase I of meiosis in human oocytes and spermatocytes by using cytogenetic techniques, electron microscopy, and in situ hybridization. Ultrastructural investigations revealed an ordered arrangement of nucleolar bivalents at the zygotene and pachytene stages. The end of the bivalent corresponding to the cytological satellite was consistently attached to the nuclear envelope. The fibrillar center of the nucleolus always contained rDNA chromatin fibers emanating from the secondary constriction region. Association of ribosomal genes from two bivalents in the same fibrillar center was frequently observed. Ultrastructural studies demonstrated the close proximity of chromatids in the short arm region of the involved nonhomologous acrocentrics. A breakage/reunion model based on our data can explain the formation of all observed types of Robertsonian translocations: monocentrics and dicentrics with or without rDNA.Robertsonian translocations are the most frequent form of chromosome rearrangement in man, their incidence being about 1% in the general population. They result from different modes of exchange occurring within the centromeric region of two acrocentric chromosomes, thus producing a metacentric or submetacentric element (1). In man, the chromosomal segment above the centromere is divided into three parts: the proximal short arm, the secondary constriction or stalk, which is the nucleolus organizer region (NOR), and the distal cytological satellite. The five pairs of acrocentric chromosomes share multiple copies of rRNA genes variably dispersed among the NORs (2, 3). Nonhomologous chromosomes are involved in 90% of Robertsonian translocations, and the most frequently observed are the 13;14 and the 14;21 translocations (4). Most translocations between heterologs are dicentric and devoid of Ag-positive NOR (4-8).The formation of Robertsonian translocations has been ascribed to chromatid exchange after a break between acrocentric chromosomes associated with the same nucleolus, during spermatogonial and oogonial mitosis (9). It has also been suggested that Robertsonian rearrangements result from an orderly, nonrandom process during meiotic pairing and exchange (10). Indeed, nonhomologous acrocentric chromosomes are often associated with the same nucleolus at meiotic prophase I in human spermatocytes and oocytes (11)(12)(13)(14). The nonrandom involvement of chromosomes in translocations can also be explained by an accidental meiotic recombination between partially homologous sites on nonhomologs. If the pairing is "end-to-end," crossing-over results in two recombinants, one acentric and the other dicentric (15). The two centromeres are so close to one another that they may act as a single centromere (16).Electron microscope studies provide more precise information about the relationship between the nucleolus and the acrocentric chromosomes. A connecting region of the nucleolus was reported in close association with the nucleolar chro...

Somatic pairing, endomitosis and chromosome aberrations in snakes (Viperidae and Colubridae)

“…Nonhomologous association of nucleolar chromosomes in human may be accounted for certain non-disjunctions and translocations causing diseases, as in myeloid leukemia (Ohno et al 1961). That model was supported by further studies using the electron microscope to study human meiotic cells (Stahl et al 1983). Moreover, the analysis of Robertsonian translocations in mice indicated that fusion of nucleoli is not the key factor predisposing to centric fusions (Miller et al 1978).…”

Theoretical bases for karyotype evolution. II. The fusion burst in man and mouse.

“…Mechanisms for centric fusion in man have been proposed by Kurnit (1979), Stahl et al (1983), and Guichaoua et al (1986). These models, despite outward telomeres (or more precisely telomere regions).…”

Molecular cytogenetic mapping of Cucumis sativus and C. melo using highly repetitive DNA sequences

“…Blocks of satellite DNA or rDNA sequences are often assumed to constitute preferential breaking points, particularly in the rDNA clusters (Hall and Parker 1995). In humans, the most common structural rearrangements are Robertsonian translocations involving the NOR-bearing chromosomes (Stahl et al 1983;Choo et al 1988). …”