Effect of double insertion of homogeneously stained regions in chromosome 1 of the house mouse on recombination frequency

By means of genetic and cytogenetic analysis, the effect of cis heterozygosity for two insertions--Is(HSR; 1C5)1Icg and Is (HSR; 1E3)2Icg was studied. It was shown that the proximal point of Is is situated 8 cM distally from the ln gene. Crossing over is completely suppressed in the intermedial part of Chr. 1, where a single chiasma appears in normal mice. The frequency of double chiasmata in heterozygotes is significantly increased. They are localized at precentromeric and pretelomeric parts of Chr. 1. It is supposed that recombination block in the central region leads to a shift of the potential chiasmata in telomeric regions. This shifted telomeric chiasmata, in turn, allow the appearance of the second chiasmata in the centromeric region.     

Effect of heterozygosity for insertions of homogeneously stained regions in chromosome 1 of the house mouse on synapsis in meiotic prophase

Electron microscope analysis of surface-spread synaptonemal complexes (SC) in oocytes and spermatocytes from double cis heterozygotes for Is(HSR; 1C5)1Icg and Is(HSR; 1E3)2Icg was carried out. Aberrant chromosomes were isolated from the feral population of Mus musculus musculus of Novosibirsk. They contain homogeneously stained regions of total length of about 30% of Chr 1 mitotic metaphase. Heteromorphic bivalents of Chr1 with different lengths of the lateral elements of SC and the loop in the intermedial position were revealed in 4.4% spermatocytes and 20% oocytes of heterozygous animals. The loop size depends on the stage of meiosis: it is maximal at late zygotene and decreases up to disappearance during pachytene.     

Synapsis in single and double heterozygotes for partially overlapping inversions in chromosome 1 of the house mouse

Electron microscopic (EM) analysis of synaptonemal complexes (SC) in single and double heterozygotes for the partially overlapping inversions In(1)1Icg, In(1)1Rk and In(1)12Rk in chromosome 1 of the house mouse reveals that synapsis and synaptic adjustment are dependent on the size and location of the inversions and interaction between the latter. In(1)1Icg contains insertions of the inverted repeats Is(HSR;1C5)1Icg and Is(HSR;1D)2Icg and an inverted euchromatic region. Synaptic adjustment of the D-loops by shortening of the asynapsed segments of the lateral elements belonging to the insertions occurs at the late zytogene to early pachytene stage. Synaptic adjustment of the inversion loops takes place at early to late pachytene. A delay in adjustment was found in the double heterozygotes In(1)1Icg/In(1)1Rk and In(1)1Icg/In(1)12Rk. A correspondence between the lifespan of asynapsis in inverted regions and the probability of association of XY and heteromorphic bivalents was revealed.     

Synapsis in single and double heterozygotes for partially overlapping inversions in chromosome 1 of the house mouse

Electron microscopic analysis of synaptonemal complexes (SC) in single and double heterozygotes for the partially overlapping inversions In(1)1Icg, In(1)1Rk and In(1)12Rk in the Chromosome 1 of the house mouse reveals a dependence of synapsis and synaptic adjustment on the size and location of the inversions and their interaction. In(1)1Icg contains the insertions of inverted repeats Is(HSR: 1C5)1Icg and Is(HSR: 1I)2Icg as well as inverted euchromatic region. The synaptic adjustment of the D loops by shortening of asynapsed parts of the lateral elements of SC belonging to the insertions occurs at late zygotene-early pachytene stage. After that the synaptic adjustment of the inversion loops takes place. A delay in adjustment was found in diheterozygotes In(1)1Icg/In(1)1Rk and In(1)1Icg/In(1)12Rk. Morphological alterations of the asynapted terminal segments of lateral elements preventing synaptic adjustment were found in single and double heterozygotes for In(1)1Rk and In(1)12Rk. Correspondence between the size of asynapted regions and the probability of association of XY and heteromorphic bivalents was revealed.     

Synapsis and recombination in inversion heterozygotes

Inversion heterozygotes are expected to suffer from reduced fertility and a high incidence of chromosomally unbalanced gametes due to recombination within the inverted region. Non-homologous synapsis of the inverted regions can prevent recombination there and diminish the deleterious effects of inversion heterozygosity. The choice between non-homologous and homologous synapsis depends on the size of inversion, its genetic content, its location in relation to the centromere and telomere, and genetic background. In addition, there is a class of inversions in which homologous synapsis is gradually replaced by non-homologous synapsis during meiotic progression. This process is called synaptic adjustment. The degree of synaptic adjustment depends critically on the presence and location of the COs (crossovers) within the inversion loop. Only bivalents without COs within the loop and those with COs in the middle of the inversion can be completely adjusted and became linear.     

The causes of appearance of a double insertion of homogeneously staining regions in the chromosome 1 of house mouse (Mus musculus musculus)]

A high resolution analysis of G-band pattern of normal and aberrant chromosome 1 bearing two linked insertions of homogeneously staining regions (HSRs) in the house mouse (Mus musculus musculus) reveals an inverted pattern of the euchromatic region between the HSRs. On the basis of this analysis, a hypothesis on the causes for appearance of the aberrant chromosome was put forward: the double insertion is a result of inversion of the chromosome 1 of Mus musculus domesticus bearing a single long insertion. The proximal breakpoint is localized inside the HSR and the distal one--between subbands E3 and E4. From the point of view of these data, new symbols for the aberrations are proposed: Ls (HSR, 1C5) 1Icg--for the proximal insertion, Is(HSR, 1D)21cg--for the distal one, In (1) 1Icg--for the inverted region, including the bands D, E1-E3 and the insertion Is(HSR 1D)21cg.     

Double insertion of homogeneously staining regions in chromosome 1 of wild Mus musculus musculus: effects on chromosome pairing and recombination

An examination of the meiotic pattern of chromosome 1 isolated from a feral mouse population and containing a double insertion (Is) of homogeneously staining regions (HSRs) was carried out. The region delineated by the proximal breakpoint of Is(HSR;1C5) 1Icg and the distal breakpoint of Is(HSR;1E3)2Icg is desynapsed during the early pachytene stage and heterosynapsed at the midpachytene, as shown by electron microscopic analysis of synaptonemal complexes. The HSRs have no effect on the segregation of chromosome 1 in heterozygous mice. The lack of homosynapsis in the region under study causes chiasmata redistribution in heteromorphic bivalents. In normal males, single chiasmata are located in the medial part of the chromosome. In heterozygotes, this segment is heterosynapsed and unavailable for recombination. This leads to a significant decrease in the frequency of bivalents bearing single chiasmata. The total number of chiasmata per bivalent is much higher in heterozygous males than in normal ones. The recombination frequency between proximal markers fz and In also is higher in heterozygous animals. The increase in the total chiasma number in the heteromorphic bivalent is due to the addition of double chiasmata located mostly at precentromeric and pretelomeric regions of the chromosome.     

Synapsis and synaptic adjustment in an infertile human male heterozygous for a pericentric inversion in chromosome 1

Summary Synapsis and synaptic adjustment were analyzed, using electron microscopy in silver stained surface microspreads of inversion-bearing spermatocytes, in an infertile human male with an inherited pericentric inversion in chromosome 1. Possible reasons for his infertility are discussed.     

Ultrastructure of the centrometric regions of mouse chromosomes in metaphase chromosomes and interphase nuclei]

The chromatin ultrastructure was studied in the centromeric region of mitotic chromosomes and in interphase nuclei of mouse cells after differential staining on C-band. A new method is suggested to study centromeric region of chromosomes treated by the Giemsa banding technique. Fibers of chromosomes appeared to be packed denser in the centromeric regions of mitotic chromosomes than in arms. The disposition of chromatin fibers in the centromeric chromocentres of interphase nuclei is the same as in the centromeric regions of mitotic chromosomes.     

A new variant of chromosome 1 in the house mouse

In wild mouse populations of Siberia, animals with a new variant of chromosome 1 were found. The total length of this chromosome was 1.3 times as great as the normal homologue. The G-banding technique revealed two additional insertions Is(HSR; 1C5)1Icg and Is(HSR; 1E3)2Icg located between bands 1C5 and 1D, and 1E3 and 1E4, resp. The C-banding of both the insertions was positive and lighter than that of the centromeric heterochromatin. The size of each insertion was approximately 15% of new variant of chromosome 1. No meiotic disturbances were found in heterozygous male mice. Chromosome 1 with insertions has been introduced into the laboratory mouse stock.     

Induction of recombination between rye chromosome 1RL and wheat chromosomes

Summary The ph1b mutant in bread wheat has been used to induce homoeologous pairing and recombination between chromosome arm 1RL of cereal rye and wheat chromosome/s. A figure of 2.87% was estimated for the maximal frequency of recombination between a rye glutelin locus tightly linked to the centromere and the heterochromatic telomere on the long arm of rye chromosome 1R in the progeny of ph1b homozygotes. This equates to a gametic recombination frequency of 1.44%. This is the first substantiated genetic evidence for homoeologous recombination between wheat and rye chromosomes. No recombinants were confirmed in control populations heterozygous for ph1b. The ph1b mutant was also observed to generate recombination between wheat homoeologues.     

Meiotic drive of the aberrant chromosome 1 in the house mouse

Animals with aberrant chromosome 1 carrying one or two large insertions were earlier described in natural populations of Mus musculus. In the present work, inheritance of the aberrant chromosome 1 from the Yakutsk population was investigated. It was shown that 80-85% of the progeny from heterozygous females received chromosome 1 with insertions. From chromosomal analysis of blastocytes and oocytes at the MII stage, it was concluded that the preferential distribution of the aberrant chromosome into oocytes during the first and especially, the second meiotic divisions is relevant to the segregation distortion observed. The mechanism of this powerful meiotic drive is discussed.     

Synaptic interrelationships between the segments of the heteromorphic bivalent in double heterozygotes for paracentric inversions in chromosome 1 of the house mouse

Electron microscopic analysis of synaptonemal complexes in bouble heterozygotes for the partially overlapping inversions In(1) 1Rk and In(1)12Rk in chromosome 1 of the house mouse was carried out. A great variety of synaptic configurations with complicated combinations of homologously and non-homologously paired segments was observed. Analysis of these configurations revealed at least five independent pairing regions in chromosome 1. Interrelationships between these regions with respect to their pairing ability were estimated. Pairings in the distal non-inverted segment and in inversions inhibit each other, while pairing in either inverted segment facilitates synapsis in the other. In other words, pairing initiations in different parts of the same bivalent are not independent events.by H.C. MacgregorDedicated to Dr. Ann Chandley in view of her important contributions to the study of meiosis     

A long-range repeat cluster in chromosome 1 of the house mouse, Mus musculus, and its relation to a germline homogeneously staining region.

The laboratory mouse C57BL genome contains about 50 copies of a long-range repeat DNA family clustered in the C-D region of chromosome 1. The repeat length is more than 50 kb and includes sequences homologous to at least two mRNAs. There are small differences in the copies of this repeat family such as restriction site mutations and gross differences like rearrangements and insertions of LINE1 elements. A germline homogeneously staining region occurring as a chromosome 1 polymorphism in many feral populations of the house mouse is an amplified version of this long-range repeat cluster.     

DNA copy number amplifications in sarcomas with homogeneously staining regions and double minutes

To identify DNA amplifications in sarcomas, comparative genomic hybridization was performed on 27 cases that were likely to display high-level DNA copy number gains. In all cases, chromosome banding analysis had revealed homogeneously staining regions or double minutes, i.e., cytogenetic signs of gene amplification. In most cases, gains predominated over losses. Low-level amplifications (ratio 1.3:1.5) were seen in 20 cases. High-level amplifications (ratio >1.5) exceeded the frequencies seen in published, unselected sarcomas of similar histotypes and were detected in 16 tumors: 4/4 osteosarcomas, 5/8 malignant fibrous histiocytomas, 3/7 leiomyosarcomas, 1/2 myosarcomas, 0/1 liposarcoma, 0/1 rhabdomyosarcoma, 1/1 pleomorphic sarcoma, 0/1 myxofibrosarcoma, 1/1 malignant mesenchymona, and 1/1 malignant schwannoma, with two to four chromosomal regions involved in nine tumors. Recurrent amplifications involved 1p33-p32, 5p15-p14, 7pter-p12, 7q21-qter, 8q21.3-qter, 11q22-q23, 16p13.2-p12, 19q12-q13.1, 20q11.2-qter, and 22q12-q13. Most of the recurrent gains/amplifications we detected have been reported in sarcomas previously. A novel gain/amplification was seen at 2q14.3-q21 in five cases of four sarcoma types. The disparate pattern of amplified sequences, the poor correspondence between the localization of low- and high-level amplifications, and the chromosomal position of homogeneously staining regions suggest the involvement of many genes in the amplifications and that the genes rarely maintain their native position in these tumors.