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.     

Familial double pericentric inversion of chromosome 5 with some features of cri-du-chat syndrome

Fluorescence in situ hybridization analysis was performed to characterize a complex pericentric inversion involving chromosome 5 in a mother and son. The mother had hypertelorism, epicanthal folds, and mild mental deficiency while the son had additional anomalies that have been observed in patients with cri-du-chat syndrome. Both individuals were found to have an identical double pericentric inversion [inv5(p15.1q31(inv5(p14q12)))]. Neither inversion breakpoint mapped near the chromosomal regions implicated in the cri-du-chat syndrome. The phenotype of the son suggests that the inversion process may have affected the expression of some of the cri-du-chat syndrome genes, suggestive of a genomic imprinting or penetrance effect. Received: 24 April 1995 / Revised: 1 September 1995     

Effects of inversion perturbation after step down on the latency of the peroneus longus and peroneus brevis

The purpose of this investigation was to determine the effect of different types of ankle sprains on the response latency of the peroneus longus and peroneus brevis to an inversion perturbation, as well as the time to complete the perturbation (time to maximum inversion). To create a forced inversion moment of the ankle, an outer sole with fulcrum was used to cause 25 degrees of inversion at the ankle upon landing from a 27 cm step-down task. Forty participants completed the study: 15 participants had no history of any ankle sprain, 15 participants had a history of a lateral ankle sprain, and 10 participants had a history of a high ankle sprain. There was not a significant difference between the injury groups for the latency measurements or the time to maximum inversion. These findings indicate that a previous lateral ankle sprain or high ankle sprain does not affect the latency of the peroneal muscles or the time to complete the inversion range of motion.     

The effect of face inversion on activity in human neural systems for face and object perception

The differential effect of stimulus inversion on face and object recognition suggests that inverted faces are processed by mechanisms for the perception of other objects rather than by face perception mechanisms. We investigated the face inversion using functional magnetic resonance imaging (fMRI). The principal effect of face inversion on was an increased response in ventral extrastriate regions that respond preferentially to another class of objects (houses). In contrast, house inversion did not produce a similar change in face-selective regions. Moreover, stimulus inversion had equivalent, minimal effects for faces in in face-selective regions and for houses in house-selective regions. The results suggest that the failure of face perception systems with inverted faces leads to the recruitment of processing resources in object perception systems, but this failure is not reflected by altered activity in face perception systems.     

Evaluation of the genomic extent of effects of fixed inversion differences on intraspecific variation and interspecific gene flow in Drosophila pseudoobscura and D. persimilis

There is increasing evidence that chromosomal inversions may facilitate the formation or persistence of new species by allowing genetic factors conferring species-specific adaptations or reproductive isolation to be inherited together and by reducing or eliminating introgression. However, the genomic domain of influence of the inverted regions on introgression has not been carefully studied. Here, we present a detailed study on the consequences that distance from inversion breakpoints has had on the inferred level of gene flow and divergence between Drosophila pseudoobscura and D. persimilis. We identified the locations of the inversion breakpoints distinguishing D. pseudoobscura and D. persimilis in chromosomes 2, XR, and XL. Population genetic data were collected at specific distances from the inversion breakpoints of the second chromosome and at two loci inside the XR and XL inverted regions. For loci outside the inverted regions, we found that distance from the nearest inversion breakpoint had a significant effect on several measures of divergence and gene flow between D. pseudoobscura and D. persimilis. The data fitted a logarithmic relationship, showing that the suppression of crossovers in inversion heterozygotes also extends to loci located outside the inversion but close to it (within 1-2 Mb). Further, we detected a significant reduction in nucleotide variation inside the inverted second chromosome region of D. persimilis and near one breakpoint, consistent with a scenario in which this inversion arose and was fixed in this species by natural selection.     

A dicentric recombinant 9 derived from a paracentric inversion: phenotype, cytogenetics, and molecular analysis of centromeres.

A 4-year-old girl with multiple malformations and severe developmental delay has been shown to have a karyotype of 46,XX-9,+rec(9),dup p,inv(9) (q22.1q34.3)mat, with duplication 9pter-q22.1 and deficiency 9q34.3-qter. This case confirms that a stable recombinant chromosome can result from a paracentric inversion. The recombinant was derived by two crossovers, one within the inversion loop and a second outside the inversion loop, between 9q21 and the beginning of the meiotic inversion at 9q22.1. In 87 cells the rec(9) had one Cd-positive primary constriction. In 13 cells the rec(9) had two primary constrictions; in 12 of these cells there was one Cd-positive centromere, and in one of these cells both primary constrictions were Cd-positive. Nuclear projections were observed in 10% of fibroblast interphase cells harvested in situ, suggesting that there was some spindle-fiber activity of the "latent" centromere. In situ hybridization with a centromere-specific probe (p82H) and a satellite III probe (L6) revealed no differences between the two C-band regions of the rec(9) and the normal 9 or inverted 9 chromosomes.     

Sperm size abnormalities in homozygous and heterozygous In(5)9Rk mice.

Sperm abnormalities were scored in In(5)9Rk homozygotes, heterozygotes and in the inbred strains, C57BL/6J, C3H/HeJ, DBA/2J and JUFaCt, used to produce the geterozygotes. The sperm abnormalities of the inversion heterozygotes were remarkable, about 40% were either double-headed or abnormally large in size. The double-headed sperm had head dimensions similar to those of normal-sized sperm, but the large sperm heads were 1.2 times longer and 1.3 times wider and presumably had twice the usual nuclear volume. This observation suggests that the anaphase bridge formed in inversion heterozygotes resulting from the paracentric inversion may constitute an impediment to cytokinesis and may lead to two genomes being packaged into a single sperm. If this is a general phenomenon, sperm morphology may provide a useful screen for paracentric inversions.     

基于SWCI-NDVI特征空间的县域耕地地力遥感反演

利用遥感反演县域耕地地力状况,快速、准确、高效地实现耕地定级,是区域耕地资源利用与管理的客观需求.本研究以东平县为研究区,利用Landsat-TM卫星影像和耕地地力评价资料,构建以地表含水量指数(SWCI)、归一化植被指数(NDVI)为特征参量的水分植被地力指数(MVFI),进而优选得到最佳反演模型,并在县域空间上进行...     

Inversion polymorphism in the malaria mosquito Anopheles messeae. VI. Local selection and 3-dimensional differentiation of the inversion gene complexes for fertility

A field experiment was carried on with the view of compulsory change of the frequency of chromosomal inversion (2R1) in the population of Anopheles messeae from the centre of the area. Quick return of the population to the original structure was observed. This confirmed that the local differentiation of chromosomal polymorphism is supported by natural selection. The fertility of the females was shown to be connected with the inversion polymorphism. The females with inversion complexes of genes of the "northern" type (with homozygotes 2R1) had higher fertility and lower dispersion of the fertility, in comparison with those having gene complexes which prevailed in the south part of the area.     

Meiotic analysis of a pericentric inversion, inv(7) (p22q32), in the father of a child with a duplication-deletion of chromosome 7

In a family in which a large pericentric inversion of chromosome 7 is segregating, two of the four progeny of inversion heterozygotes show severe psychomotor retardation and have the karyotype 46,XX,rec(7),dup q,inv(7)(p22q32), derived from crossing-over within the inversion. Meiotic analysis in one of the heterozygotes revealed no evidence of inversion loops in well-spread pachytene cells. In approximately 20% of cells in diakinesis, the presumptive bivalent 7 had only one chiasma. Two alternatives to the reversed loop mode of meiotic pairing of inversions are proposed. Review of the literature supports the view that "small" pericentric inversions have a much better genetic prognosis than "large" pericentric inversions.     

一例特殊inv(Y)形成机理的研究

应用双色荧光原位杂交的方法,国内首次报道一例特殊inv(Y)异常的性质,探讨Y染色体倒位结构异常的形成机理以及与习惯性流产临床表型的关系。应用 Biotin-11-dUTP标记的Y染色体短臂断裂点Yp11.3探针（编号889）和CY3标记的Y染色体长臂断裂点Yq12远端异染色质区探针(编号PY3.4),对1例G显带核型分析为[46, XY(90%) / 46, X, inv(Y)(p11.3;q12)]的平衡易位携带者进行双色荧光原位杂交研究。双色FISH结果显示,该易位携带者异常核型比例为22%,稍高于G显带分析中确定的比例。而且,除G显带检测出的倒位类型外,又有两种类型的倒位,其中涉及到常规显带技术难以检测出的染色单体型倒位。3种倒位类型的存在说明该患者inv(Y)断裂点呈不均一性。FISH技术是一种能准确可靠检测出染色体倒位形成的重要手段。      

Effects of Chromosomal Inversion on Cell Fitness in Escherichia Coli K-12

In an effort to learn what factors might mitigate the establishment of Escherichia coli variants bearing major chromosomal rearrangements, we have examined the effects on cell growth of two inversions between rRNA operons. One of these inversions, IN(rrnD-rrnE), had been propagated in a commonly used subline of E. coli K-12 for approximately 30 yr before its discovery, a fact that illustrates the absence of obvious detrimental effects associated with the inversion. We found that culturing under conditions requiring repeated transition from stationary phase to rapid growth led to the replacement of IN(rrnD-rrnE) cells by cells that had undergone either of two types of additional chromosomal inversion: one type fully restored the wild-type order, while the other partially restored it. The partial reinversion was also between rrn operons, but it left a small transposition. The tendency for overgrowth by these revertants persisted through several rounds of periodic selection. In contrast, the other inversion, IN(rrnG-rrnE), was associated with severe, detrimental effects. The effects of IN(rrnG-rrnE) were also alleviated by full or partial reinversion. The probable relationship between the severity of the effects caused by the inversions and the degree of displacement of the replication origin is discussed. Spontaneous inversion events between rrn operons separated by 18% of the chromosome were estimated to occur at a frequency of roughly 10(-5). If extended to natural situations, the growth disadvantage together with the relatively high frequency of reinversion suggest that clones of cells with an inversion between these rrn operons would be readily overgrown by revertants.     

Direct evidence for suppression of recombination within two pericentric inversions in humans: a new sperm-FISH technique.

Crossover within a pericentric inversion produces reciprocal recombinant chromosomes that are duplicated/deficient for all chromatin distal to the breakpoints. In view of this fact, a new technique is presented for estimating the frequency of recombination within pericentric inversions. YAC probes were selected from within the q- and p-arm flanking regions of two human inversions, and two-color FISH analysis was performed on sperm from heterozygous inversion carriers. A total of 6,006 sperm were analyzed for chromosome 1 inversion (p31q12), and 3,168 were analyzed for chromosome 8 inversion (p23q22). Both inversions displayed suppression of crossing-over, although the amount of suppression differed between the two inversions. The recombination frequency of 13.1% recorded for chromosome 8 inversion was similar to the frequency of 11.4% previously estimated by the human/hamster-fusion method. For chromosome 1 inversion, the recombination frequency of 0. 4% reported here was below the limits of detection of the fusion technique. The simplicity of the FISH technique and the ease of scoring facilitate analysis of a sample-population size much larger than previously had been possible.     

Identification, cloning, and sequencing of piv, a new gene involved in inverting the pilin genes of Moraxella lacunata.

Moraxella lacunata is a bacterium that is a causative agent of human conjunctivitis and keratitis. We have previously cloned the Q and I pilin (formerly called beta and alpha pilin) genes of Moraxella bovis and determined that an inversion of 2 kilobases (kb) of DNA determines which pilin gene is expressed. Using an M. bovis pilin gene as a hybridization probe to screen a lambda ZAP library of M. lacunata DNA, we have isolated a clone that not only contains the entire type 4 pilin gene inversion region of M. lacunata but inverts the 2-kb region on a plasmid subclone (pMxL1) in Escherichia coli. Deletion derivatives of pMxL1 yielded some plasmids that still had the entire inversion region but were phase locked into one or the other of the two potential orientations. Similarly, insertions of a 2-kb streptomycin-resistant element (omega) within some regions outside of the inversion also resulted in phase-locked plasmids. These deletions and insertions thus localize a probable invertase necessary for the inversion event. The region was sequenced, and an open reading frame with over 98% DNA sequence homology to an open reading frame that we previously found in M. bovis and called ORF2 appeared to be a strong candidate for the invertase. This conclusion was confirmed when a plasmid containing the M. bovis ORF2 supplied, in trans, the inversion function missing from one of the M. lacunata phase-locked inversion mutants. We have named these putative invertase genes piv(ml) (pilin inversion of M. lacunata) and piv(mb) (pilin inversion of M. bovis). Despite previously noted sequence similarities between the M. bovis sites of inversion and those of the Hin family of invertible segments and a 60-base-pair region within the inversion with 50% sequence similarity to the cin recombinational enhancer, there is no significant sequence similarity of the Piv invertases to the Hin family of invertases.     

Large chromosomal inversion correlated with spectinomycin resistance in Lactococcus lactis subsp. lactis bv. diacetylactis S50

A large chromosomal inversion that confers resistance to high concentrations of the antibiotic spectinomycin in Lactococcus lactis subsp. lactis bv. diacetylactis S50 was identified by pulsed field gel electrophoresis. The same type of inversion was identified in 4 independent experiments and in 4 different derivatives of strain S50, indicating the same position and the same mechanism of recombination as a response to antibiotic selective pressure in all derivatives. An analysis of ribosomal operons in strain S50 and mutants revealed that ribosomal operons are not endpoints of the recombination. Spectinomycin-resistant mutants appeared in a population of S50 derivatives at a high frequency of 2 x 10(-7). These spectinomycin-resistant mutants were not able to compete successfully with the wild-type strain during 25 generations (48 h) of co-culture in vitro, indicating that inversion had a significant fitness cost. Results demonstrate that as a mechanism of genome plasticity, inversion can be directly involved in one-step development of the adaptation to a high concentration of spectinomycin.     

Some ultrastructural features of Volvox,with particular reference to the phenomenon of inversion

Summary Some features of the ultrastructure of Volvox are described. Golgi bodies were often associated with the endoplasmic reticulum (ER), and the two basal bodies appeared to be accompanied by two probasal bodies. A few vegetative cells were binucleate. All cells examined had a peripheral cytoskeleton of microtubules which was particularly well developed in the cells of sperm packets. During inversion of a colony, the cells elongated considerably, possibly due to the increased length of these peripheral microtubules; the cell profile also became some-what narrowed at the inner edge of the flexing colony. Cytoplasmic connections were large and numerous in young coenobia, but were generally absent in older vegetative colonies; by inversion, they had become confined to the chloroplast end of the cells where they seemed to act as hinges. Elements of the ER ran through these interconnections, possibly providing an intercellular communication network needed for the coordinated activity of inversion. A new structural feature was discovered in the form of circular (or possibly spiral) striations on the plasmalemma around these cytoplasmic connections. They were detectable just before inversion, and were most pronounced immediately after.     

Acquired pericentric inversion of chromosome 9 in acute myeloid leukemia

Pericentric inversion of chromosome 9 involving the qh region is relatively common as a constitutional genetic aberration without any apparent phenotypic consequences. However, it has not been established as an acquired abnormality in cancer. Among the three patients reported so far in the literature with acquired inv(9), only one had acute myeloid leukemia (AML). Here we describe an unique case where both chromosomes 9 presented with an acquired pericentric inversion with breakpoints at 9p13 and 9q12 respectively, in a AML patient with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region and including the p16 gene. The constitutional karyotype was normal. This is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML. The possible significance of this inversion is discussed.     

The Effect of Inversion at 8p23 on BLK Association with Lupus in Caucasian Population

To explore the potential influence of the polymorphic 8p23.1 inversion on known autoimmune susceptibility risk at or near BLK locus, we validated a new bioinformatics method that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion in a Caucasian population. Methods: Principal components analysis (PCA) was performed using markers inside the inversion territory followed by k-means cluster analyses on 7416 European derived and 267 HapMaP CEU and TSI samples. A logistic regression conditional analysis was performed. Results: Three subgroups have been identified; inversion homozygous, heterozygous and non-inversion homozygous. The status of inversion was further validated using HapMap samples that had previously undergone Fluorescence in situ hybridization (FISH) assays with a concordance rate of above 98%. Conditional analyses based on the status of inversion were performed. We found that overall association signals in the BLK region remain significant after controlling for inversion status. The proportion of lupus cases and controls (cases/controls) in each subgroup was determined to be 0.97 for the inverted homozygous group (1067 cases and 1095 controls), 1.12 for the inverted heterozygous group (1935 cases 1717 controls) and 1.36 for non-inverted subgroups (924 cases and 678 controls). After calculating the linkage disequilibrium between inversion status and lupus risk haplotype we found that the lupus risk haplotype tends to reside on non-inversion background. As a result, a new association effect between non-inversion status and lupus phenotype has been identified ((p = 8.18×10⁻⁷, OR = 1.18, 95%CI = 1.10–1.26). Conclusion: Our results demonstrate that both known lupus risk haplotype and inversion status act additively in the pathogenesis of lupus. Since inversion regulates expression of many genes in its territory, altered expression of other genes might also be involved in the development of lupus.     

Human chromosomal polymorphism. IV. Chromosomal Q polymorphism in Russians living in Kirghizia

Summary Chromosomal Q polymorphism was studied in 200 Russian individuals (94 females and 106 males) living in Kirghizia. Of the 200 individuals, 191 had chromosomal Q polymorphic variants, while nine (4.5%) had no Q bands with fluorescence levels 4 and 5. The mean number of Q variants per individual ranged from 0 to 7, with a mean of 2.9. There were no differences in the frequency of Q variants between sexes. The observed homo- and heteromorphic frequencies completely agreed with those predicted by the law of Hardy-Weinberg. Of the 200 individuals, 12 (6.0%) had pericentric inversion of the Q band in chromosome 3, one individual (0.5%) having a homomorphic form of this inversion. The possible selective value of chromosomal Q heterochromatin material in the adaptation of human populations to extreme environmental factors, in particular to cold, and the possible taxonomic value of inverted Q heterochromatin bands in chromosome 3 in ethnic anthropology, are discussed.     

Cin-mediated recombination at secondary crossover sites on the Escherichia coli chromosome.

The Cin recombinase is known to mediate DNA inversion between two wild-type cix sites flanking genetic determinants for the host range of bacteriophage P1. Cin can also act with low frequency at secondary (or quasi) sites (designated cixQ) that have lower homology to either wild-type site. An inversion tester sequence able to reveal novel operon fusions was integrated into the Escherichia coli chromosome, and the Cin recombinase was provided in trans. Among a total of 13 Cin-mediated inversions studied, three different cixQ sites had been used. In two rearranged chromosomes, the breakpoints of the inversions were mapped to cixQ sites in supB and ompA, representing inversions of 109 and 210 kb, respectively. In the third case, a 2.1-kb inversion was identified at a cixQ site within the integrated sequences. This derivative itself was a substrate for a second inversion of 1.5 kb between the remaining wild-type cix and still another cixQ site, thus resembling a reversion. In analogy to that which is known from DNA inversion on plasmids, homology of secondary cix sites to wild-type recombination sites is not a strict requirement for inversion to occur on the chromosome. The chromosomal rearrangements which resulted from these Cin-mediated inversions were quite stable and suffered no growth disadvantage compared with the noninverted parental strain. The mechanistic implications and evolutionary relevance of these findings are discussed.