The significance of pericentric inversions of chromosome 2

Summary Thirteen new cases of a pericentric inversion 2 collected from different laboratories are reported. In addition 41 cases of a pericentric inversion 2 were reviewed from the literature. The pooled data were analysed using Weinberg's proband method to evaluate the risk of a carrier for either children with congenital anomalies or reproductive wastage. In the corrected sample of 166 lifeborn offspring of carriers of a pericentric inversion 2 there were five who showed phenotypic anomalies and two died a few hours after delivery. The reported anomalies are heterogeneous and probably reflect the basic risk of any couple for abnormal lifeborn offspring. There has been no observation of a lifeborn who inherited an unbalanced recombination of a parental pericentric inversion 2. A carrier of a pericentric inversion 2 obviously has an increased risk for reproductive wastage. This is indicated by (1) an increase of the rate of spontaneous abortions and (2) an increase of the rate of index patients ascertained because of previous miscarriages. The risk of a carrier of a pericentric inversion 2 for a spontaneous abortion or a stillbirth may be about twice the basic risk of the general population.     

Familial pericentric and paracentric inversions of chromosome 1

Summary We investigated 33 individuals (21 carriers) from one family with a pericentric inversion involving a large part of chromosome 1 (1p36.11q32). In addition, we investigated 15 individuals (10 carriers) from another family with a paracentric inversion of a small part of chromosome 1(1p321p36.1). In each family, the index patient was ascertained because three miscarriages had occurred. Each carrier of these inversions was phenotypically normal. If the miscarriages of the index patients are excluded, the frequency of recognized miscarriages among the carriers of childbearing age was 9% (4 of 46) for the family with pericentric inversion and 17% (4 of 23) for the family with paracentric inversion. One of the pericentric inv(1) carriers had had a stillborn daughter. The carriers of the pericentric inversion who were of childbearing age had 41 children; carriers of the paracentric inversion who were of childbearing age had 19 children. No live-born children with birth defects were observed in either family. This evidence, together with the low frequency of miscarriages, suggests that crossover within the inversion loop occurs much less frequently than might be expected from the large size of this inversion. Our investigation suggests that the risk of recognized miscarriages, stillbirths, and live-born children with recombinant chromosomes who have birth defects may be much lower for inv(1) carriers than previously reported. The risk of having a malformed child because of a recombinant chromosome is probably less than 3% for carriers of the pericentric inversion and less than 6% for the carriers of the paracentric inversion.     

Molecular cytogenetic characterization of breakpoints involving pericentric inversions of human chromosome 9

Pericentric inversions involving the secondary constriction (qh) region of chromosome 9 are considered to be normal variants. The evolutionary mechanisms and conservation of these inversions via Mendelian fashion have been investigated since the advent of banding techniques. Routine cytogenetic techniques cannot provide the fine characterization necessary to determine the type of genetic material involved in these rearrangements. Therefore, the fluorescence in situ hybridization technique with the human centromere-specific alpha satellite and the beta satellite (D9Z5) and classical satellite (D9Z1) human DNA probes were used to identify the breakpoints of chromosome 9 pericentric inversions. Four unique types of pericentric inversions involving the 9qh region were observed, and the mechanism may be due to breakage and reunion at the proposed breakpoints. They are: type A inversions consist of breakpoints within the alpha and beta satellite DNA regions; type B consist of breakpoints within the beta satellite DNA region and band 9q13; type C involve breakage within the beta and classical satellite DNA regions, and type D have breakpoints within the alpha and classical satellite DNA regions. Obviously, reshuffling of satellite DNA sequences has occurred, which has given rise to a variety of heteromorphisms whose clinical significance remains obscure. Received: 21 December 1995 / Revised: 30 May 1996     

Paracentric inversions in human chromosome 7

Summary A paracentric inversion (7)(q11q22) and mosaicism 46,XX/45,X was detected in a female with minor malformations. The same inversion was observed in the mother of the patient. The analysis of high resolution banded chromosmes revealed no visible imbalance in the inverted long arm of the chromosome 7. All published cases of paracentric inversions in the human chromosome 7 are reviewed and the relationship between this inversion and the occurrence of an aneuploidy of the sex chromosomes is discussed.     

Frequency of chromosome polymorphism for pericentric inversions and B-chromosomes in Spanish populations of Rattus rattus frugivorus

Inversion frequencies in chromosomes 16 and 18 and B-chromosome frequency have been studied in three populations of Rattus rattus frugivorus.In two of these, Cuenca and San Pedro del Pinatar, the frequencies of homozygous and heterozygous individuals do not differ significantly from the Hardy-Weinberg equilibrium for both chromosome pairs. By contrast, in the Vega de Granada population there are fewer heterozygous and more homozygous individuals than expected on the basis of the Hardy-Weinberg distribution, although the frequency distributions of karyotypes in these three populations are not significantly different.In relation to the B chromosome, the Cuenca and San Pedro populations have frequencies of B-carrying animals of 0.25 and 0.22 respectively, the Vega de Granada population of 0.80.     

Homozygous-viable pericentric inversions for genetic control of Lucilia Cuprina

Summary The isolation of homozygous-viable pericentric inversions for inclusion in field-female killing (FK) systems in Lucilia cuprina is described. From 7,236 irradiated chromosomes screened, 16 pericentric inversions were isolated. Four of these were viable as homozygotes. One of these, In (3LR) 14, possesses the properties required for inclusion in FK systems (tight linkage of one inversion break-point to the white-eye gene and substantial genetic exchange within the inversion in heterozygous females).     

A large pericentric inversion of human chromosome 8.

A large pericentric inversion, inv(8) (p11q24), was ascertained in a male investigated because his wife had had repeated miscarriages. The inversion segregated in 3 generations of the family, and no chromosomally unbalanced offspring were detected. The miscarriage and the inversion could not be causally related.     

Molecular characterization of the pericentric inversion of chimpanzee chromosome 11 homologous to human chromosome 9

In addition to the fusion of human chromosome 2, nine pericentric inversions are the most conspicuous karyotype differences between humans and chimpanzees. In this study we identified the breakpoint regions of the pericentric inversion of chimpanzee chromosome 11 (PTR 11) homologous to human chromosome 9 (HSA 9). The break in homology between PTR 11p and HSA 9p12 maps to pericentromeric segmental duplications, whereas the breakpoint region orthologous to 9q21.33 is located in intergenic single-copy sequences. Close to the inversion breakpoint in PTR 11q, large blocks of alpha satellites are located, which indicate the presence of the centromere. Since G-banding analysis and the comparative BAC analyses performed in this study imply that the inversion breaks occurred in the region homologous to HSA 9q21.33 and 9p12, but not within the centromere, the structure of PTR 11 cannot be explained by a single pericentric inversion. In addition to this pericentric inversion of PTR 11, further events like centromere repositioning or a second smaller inversion must be assumed to explain the structure of PTR 11 compared with HSA 9.     

Molecular characterisation of the pericentric inversion that distinguishes human chromosome 5 from the homologous chimpanzee chromosome

Human and chimpanzee karyotypes differ by virtue of nine pericentric inversions that serve to distinguish human chromosomes 1, 4, 5, 9, 12, 15, 16, 17, and 18 from their chimpanzee orthologues. In this study, we have analysed the breakpoints of the pericentric inversion characteristic of chimpanzee chromosome 4, the homologue of human chromosome 5. Breakpoint-spanning BAC clones were identified from both the human and chimpanzee genomes by fluorescence in situ hybridisation, and the precise locations of the breakpoints were determined by sequence comparisons. In stark contrast to some other characterised evolutionary rearrangements in primates, this chimpanzee-specific inversion appears not to have been mediated by either gross segmental duplications or low-copy repeats, although micro-duplications were found adjacent to the breakpoints. However, alternating purine–pyrimidine (RY) tracts were detected at the breakpoints, and such sequences are known to adopt non-B DNA conformations that are capable of triggering DNA breakage and genomic rearrangements. Comparison of the breakpoint region of human chromosome 5q15 with the orthologous regions of the chicken, mouse, and rat genomes, revealed similar but non-identical syntenic disruptions in all three species. The clustering of evolutionary breakpoints within this chromosomal region, together with the presence of multiple pathological breakpoints in the vicinity of both 5p15 and 5q15, is consistent with the non-random model of chromosomal evolution and suggests that these regions may well possess intrinsic features that have served to mediate a variety of genomic rearrangements, including the pericentric inversion in chimpanzee chromosome 4.     

Structure of the pericentric long arm region of the human Y chromosome.

We have analysed the sequence organization of the DNA in the pericentric region of the long arm of the human Y chromosome. The structures of one cosmid and three yeast artificial chromosome clones were determined. The region consists of a mosaic of the known 5, 48 and 68 base-pair tandemly repeated sequences and at least five novel repeated sequence families. A long range-map of approximately 3.5 x 10(6) base-pairs of genomic DNA was constructed that placed the clones between about 500 x 10(3) and 850 x 10(3) base-pairs from the long arm edge of the centromeric alphoid DNA array.     

Molecular characterization of the pericentric inversion that causes differences between chimpanzee chromosome 19 and human chromosome 17

A comparison of the human genome with that of the chimpanzee is an attractive approach to attempts to understand the specificity of a certain phenotype's development. The two karyotypes differ by one chromosome fusion, nine pericentric inversions, and various additions of heterochromatin to chromosomal telomeres. Only the fusion, which gave rise to human chromosome 2, has been characterized at the sequence level. During the present study, we investigated the pericentric inversion by which chimpanzee chromosome 19 differs from human chromosome 17. Fluorescence in situ hybridization was used to identify breakpoint-spanning bacterial artificial chromosomes (BACs) and plasmid artificial chromosomes (PACs). By sequencing the junction fragments, we localized breakpoints in intergenic regions rich in repetitive elements. Our findings suggest that repeat-mediated nonhomologous recombination has facilitated inversion formation. No addition or deletion of any sequence element was detected at the breakpoints or in the surrounding sequences. Next to the break, at a distance of 10.2-39.1 kb, the following genes were found: NGFR and NXPH3 (on human chromosome 17q21.3) and GUC2D and ALOX15B (on human chromosome 17p13). The inversion affects neither the genomic structure nor the gene-activity state with regard to replication timing of these genes.     

Familial pericentric inversion of chromosome 12

Summary A pericentric inversion in one of the chromosomes 12, found in two families living in the same region, is deseribed. This inversion was detected during routine chromosomal analysis in two separate laboratories. The breakpoints were at 12p112 and 12q13. The inverted segment represented approximately 20% of the length of chromosome 12. Twenty nine descendants of carriers of the inversion were investigated, and the inversion was present in 23 of them. The other six descendants showed a normal karyotype. After correction for sample bias with the single selection scheme, a segregation ratio of 3:1 was estimated, indicating that the inverted chromosome 12 was preferentially transmitted. All the carriers of the inversion were phenotypically normal, without noticeable fertility disturbances.     

Robertsonian rearrangements and pericentric inversions in Scaridae fish (Perciformes)

The parrotfishes (family Scaridae) are comprised of the subfamilies Sparisomatinae and Scarinae. They are important agents of marine bioerosion, which rework the substrate with their beaklike jaws. Despite their importance, there are no published cytogenetic data on this group. We made cytogenetic analyses of Sparisoma axillare (Sparisomatinae) and Scarus trispinosus [corrected] (Scarinae) from the Brazilian coast. Differentiation in the diploid number in S. axillare compared to the basal karyotype of the Perciformes apparently occurred due to a Robertsonian fusion, combined with pericentric inversions. S. trispinosus [corrected] presented a conserved diploid number, but showed considerable structural karyotypic changes, resulting mainly from pericentric inversions. The Ag-NOR sites were unique and located on the short arm of the 1st subtelocentric pair in both species (possibly homeologous), corresponding to the 11th pair in S. axillare and the 9th pair in S. trispinosus [corrected] The constitutive heterochromatin is reduced in these species and is distributed in centromeric and pericentromeric regions in most of the chromosomes. The low fundamental number compared to the Scarus genus suggests a more basal condition for Sparisoma. The chromosome formula in S. trispinosus [corrected] was more diversified, deriving from large-scale pericentric inversions. Karyotypic evolution patterns observed for these representatives of the Sparisomatinae and Scarinae subfamilies, added to new data from a larger number of species, would allow us to determine if there is a tendency among the Sparisomatinae for centric fusion events.     

Mosaic pericentric inversion of chromosome 2

A pericentric inversion of chromosome number 2 in mosaic with a normal cell line is reported in a 8-year-old boy associated with slight dysmorphic syndrome and moderate mental handicap.