Genetic control of chromosome synapsis in mice heterozygous for a paracentric inversion

Frequencies of formation of inversion loops and their relative sizes were studied in laboratory mice heterozygous at paracentric inversion In1(1)Rk in chromosome 1, depending on the genetic background. Homozygotes In1/In1 were crossed with mice from five inbred strains (A/HeJ, BALB/cJ, C3H/HeJ, C57BL/6J, DBA2/J). The frequency of formation of inversion loops, their relative sizes, and the dependence of these parameters on the stage of pachitene were analyzed on electron-microscopic slides of spread spermatocytes in first-generation hybrids. It was shown that the genetic background and cross direction statistically significantly influenced the duration of individual pachitene stages and the frequency of inversion loops, but not relative loop size. Using a database on SNP distribution in the inbred strains examined, we carried out in silico mapping of genes affecting the genotype-dependent characters. We have found that the efficiency of synapsis in the inversion does not depend on interstrain differences in homology of the chromosome 1 region involved in the inversion. Genes controlling the inversion loop frequency in the inversion heterozygotes were mapped to chromosome 7, and genes controlling the duration of individual pachitene stages, to chromosomes 2 and 5.     

Spreading synaptonemal complexes from Zea mays

Four different inversion heterozygotes of maize were examined for the occurrence of synaptic adjustment. Three substages of pachytene were identified in synaptonemal complex (SC) spreads using side-by-side comparisons of chromosome squashes with two-dimensional spreads of SCs. In SC spreads, inversion loop frequency did not change substantially from early through late pachytene for any of the four inversion heterozygotes examined. In addition, the position and size of the inversion loops remained essentially constant throughout pachytene. These results indicate that synaptic adjustment of inversion loops does not occur during pachytene in Zea mays.     

Chromosomal inversion discovered in C3H/HeJ mice

Mice of the inbred mouse strain C3H/HeJ have been shown to be homozygous for a chromosomal inversion on Chromosome (Chr) 6. The inversion encompasses about 20% of the chromosome from approximately 73 Mb to approximately 116 Mb. The importance of this finding is that linkage crosses using C3H/HeJ will show no recombination in this region of Chr 6. The inversion has no apparent effect on the phenotype of C3H/HeJ mice and its presence should not affect biological studies; however, use of C3H/HeJ mice for genetic analysis of Chr 6 should be avoided or the results interpreted with the inversion in mind. The inversion has been named In(6)1J (inversion Chr 6, Jackson 1).     

Synaptonemal complex analysis of mouse chromosomal rearrangements

Synaptonemal complex (SC) analysis by electron microscopy of spermatocytes in surface microspreads was carried out in mice heterozygous for two paracentric inversions: either In(1)1RK or In(2)5Rk. Characteristic SC inversion loops are formed at synapsis in bivalents carrying the rearrangements. Although all loops were observed to be eliminated by late pachytene through synaptic adjustment, every spermatocyte at early pachytene contained a fully synapsed loop. Cells in the earliest stage of pachytene contained the longest loops and thus had undergone minimal adjustment. The SC estimates of inversion lengths and breakpoint positions in such cells corresponded well with those from mitotic chromosome banding and could be correlated with genetic maps of chromosomes # 1 and # 2, thus demonstrating the basis for the mapping of pachytene chromosomes. The regularity of loop formation and reproducibility of the SC analysis are reflected in the constant relative positions of the estimated breakpoints. The method is sensitive enough to reflect small, real, interstitial length differences between meiotic and mitotic chromosomes. The results demonstrate the feasibility and precision of detection and quantitative characterization of inversions at early meiotic prophase by SC analysis.This paper is warmly dedicated to Prof. Dr. Wolfgang Beermann, on the occasion of his 60th birthday     

Mapping of theLyb-4 gene to different chromosomes in DBA/2J and C3H/HeJ mice

Linkage has been established between the Lyb-4 alloantigen locus and the chromosome 4 markersLyb- 2 andMup- 1 using recombinant inbred (RI) strains. Only 2 of 24 BXD RI strains possess recombinant genotypes with respect to the B cell alloantigen lociLyb- 4 andLyb- 2, for an estimated recombination frequency of 0.024 ±0.019. One additional BXD RI strain was a recombinant with respect toLyb- 4 andMup- 1 (major urinary protein locus) for an estimated recombination frequency of 0.039 ± 0.026. These linkages were confirmed and further quantitated in a (C57BL/6J × DBA/2J)F₁ × C57BL/6J backcross population, in which the recombination frequency betweenLyb- 4 andMup- 1 was 0.049 ± 0.019. No recombination between the expression of Lyb-4.1 antigen and the ability of anti-Lyb-4.1 serum to suppress MLC reactivity was found, indicating that the genes controlling the antigenic determinant which is recognized with cytotoxic antibodies in anti-Lyb-4.1 serum is the same as, or is very closely linked to, the gene which is responsible for augmentation of the MLC response. In contrast, no linkage was observed between the gene controlling the Lyb-4.1 determinant andMup- 1 in RI strain and backcross mice derived from the cross of C3H/HeJ and C57BL/6J. Again, there was complete concordance between the serologically recognized determinant and the ability of anti-Lyb-4.1 serum to suppress the MLC response. Absorption of anti-Lyb-4.1 serum with C3H/HeJ, DBA/2J, and C57BL/6J lymphocytes, followed by the cytotoxic assay of the absorbed sera on lymphocytes of each of these three strains showed that serologically the Lyb-4.1 antigenic determinant on DBA/2 mice was indistinguishable from that on C3H/HeJ mice. Thus, both traits appear to be under the control of single genes in both DBA/2J and C3H/HeJ, but the C3H/HeJ gene appears to be nonallelic and unlinked to the DBA/2J gene.Abbreviations used in this paper LAD lymphocyte activating determinants - LPS lipopolysaccharide - MLC mixed lymphocyte culture - RI recombinant inbred     

Translocation and amplification of an X-chromosome DNA repeat in inbred strains of mice.

A 9-kb repetitive DNA fragment (70-38) located near the centromere of the mouse X chromosome is amplified and translocated to an autosome in different inbred strains of mice. In situ hybridization and hybrid cell studies showed that probe 70-38 is located only on the X chromosome in mouse strains A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J and SWR/J. However, in four other mouse strains the DNA sequence is found near the centromere of an autosome in addition to the X chromosome. This autosome differs among the mouse strains (chromosome 11 in C57BL/10J or ScSn, chromosome 13 in NZB/B1NJ and chromosome 17 in SJL/J and PO). In those strains where the repeated sequence is located on an autosome, it has been amplified to about 100 copies. Restriction enzyme digestion patterns suggest a common structure for 70-38 sequences in the different strains. The changes in copy number, restriction enzyme digestion patterns, and chromosomal location of 70-38 reflect a rapid genomic evolution inbred mouse strains.     

A pachytene analysis of two male-fertile paracentric inversions in chromosome 1 of the mouse and in the male-sterile double heterozygote

Meiotic studies have been made at pachytene on two paracentric inversions in chromosome 1 of the mouse. Surface-spread preparations of primary spermatocytes have been analysed at the light microscope level in males heterozygous for the inversions In(1)1Rk and In(1)12Rk and in the double heterozygote In(1)1RK/In(1)12Rk. In singly heterozygous form, neither inversion produces any serious effect on male fertility. In the double heterozygote, spermatogenesis is arrested in the majority of cells at the spermatocyte stage and males are rendered totally sterile by azoospermia. In the double heterozygote, a complex loop, indicating the inversion bivalent, is found in 90% of pachytene cells analysed. In the In(1)1Rk/+ heterozygote, a looped bivalent was seen in 47 per cent of pachytene cells but in In(1)12Rk/+ no cells containing loops could be found. -80% of pachytene spermatocytes from the In(1)1Rk/In (1)12Rk double heterozygote showed apposition of the inversion bivalent to the sex bivalent. Such an association was rarely seen in pachytene cells of either of the fertile single heterozygotes. Spermatogenic failure in the double heterozygote may be related to interference, by the inversion bivalent, with X chromosome inactivation at meiotic prophase.     

Segregation patterns of endogenous mouse mammary tumor viruses in five recombinant inbred strain sets.

We identified mouse mammary tumor proviral loci in the AKR/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and SWR/J inbred mouse strains and determined their segregation patterns in the AKXD, AKXL, BXD, BXH, and SWXL recombinant inbred strain sets. Two new Mtv loci, Mtv-29 and Mtv-30, were identified. Mtv-30 was genetically mapped to chromosome 12. Additionally, two previously identified Mtv loci, Mtv-14 and Mtv-23, were genetically mapped to chromosome 4 and chromosome 6, respectively.     

Assignment of the structural gene for argininosuccinate synthetase to proximal mouse chromosome 2

In order to develop linkage markers for the murine argininosuccinate synthetase locus (Ass-1), we have searched for restriction fragment length polymorphisms in the mouse genome using cloned sequences from the mouse arginosuccinate synthetase structural gene. Five restriction fragment length polymorphisms were found among the recombinant inbred progenitor strains AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and SWR/J. Of these, four polymorphisms were found to distinguish the SWR/J strain from the other six strains, which all had the same fragment. The fifth polymorphism revealed differences among the progenitor strains for recombinant inbred strain sets AKXL, BXD, and SWXL. The strain distribution pattern for this polymorphism indicated close linkage of Ass-1 to Hc (the fifth component of complement) on proximal mouse chromosome 2 with a recombination fraction of 0.016 and a 95% confidence interval of 0.003 to 0.054. These data place Ass-1 in a syntenic group with the genes Hc, Abl, Fpgs, and Ak-1 whose linkage has been conserved between human chromosome 9q and mouse chromosome 2.     

Dominant low responsiveness in the IgG response of mice to the complex protein antigen type 1 fimbriae from Actinomyces viscosus T14V.

Type 1 fimbriae from Actinomyces viscosus T14V, composed of a complex protein of Mr 65,000, mediate the adherence of A. viscosus T14V to the host, whereas type 1 fimbriae-specific antibodies inhibit adherence. Genetic control of the serum IgG response to type 1 fimbriae was evaluated in a series of inbred, hybrid, recombinant inbred, and back-cross mice. Mice were given i.p. injections of 10(8) A. viscosus T14V cells in saline on days 0 and 14, and IgG anti-type 1 fimbriae in sera obtained on day 26 were measured by ELISA. Segregation analysis of the responses of (BALB/cJ x A/J)F1 x A/J backcross mice suggested polygenic control. Linkage analysis in (BALB/cJ x A/J)F1 x A/J backcross and SWXL recombinant inbred mice suggested control by genes linked with H-2 and with Ly-17 and Akp-1. In several F1 hybrid strains derived from H-2-disparate high and low responder parental strains, low responsiveness was dominant. The F1 derived from the H-2-identical high and low responder strains CBA/J and C3H/HeJ was a low responder, suggesting that dominant low responsiveness was mediated by non-H-2-linked genes. A three-gene model is proposed for regulation of the type 1 fimbriae response, including an MHC-linked gene, a gene linked with Ly-17 and Akp-1 on the telomeric portion of chromosome 1, and a background gene whose linkage is unknown.     

Autosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine

We have previously reported that airway hyperresponsiveness to acetylcholine (ACh) is inherited as an autosomal recessive trait in A/J and C3H/HeJ mice and the progeny of crosses between them (FASEB J. 2: 2605-2608, 1988). In the present report, we have extended these studies by evaluating the biological variability in the airway response to 5-hydroxytryptamine (5-HT) and ACh among multiple genetically standardized inbred strains of mice. The pattern of airway responsiveness to ACh differed significantly from that of 5-HT in nine inbred strains of mice. A/J mice showed nonspecific airway hyperresponsiveness to both 5-HT and ACh. DBA/2J mice were hyperresponsive to 5-HT but not to ACh. An airway phenotype that resembled these inbred strains is termed HYPERREACTIVE. The C3H/HeJ and C57BL/6J inbred strains were minimally reactive to either ACh or 5-HT. Airway phenotypes that resembled these minimally reactive strains are termed HYPOREACTIVE. The frequency of HYPERRACTIVE and HYPOREACTIVE offspring from crosses between A/J and C3H/HeJ mice or DBA/2J and C57BL/6J mice is consistent with a single autosomal recessive gene, primarily determining airway hyperresponsiveness to 5-HT. We report linkage studies which suggest that these genes are not closely linked and that 5-HT and ACh airway hyperresponsiveness is inherited independently. The results of these studies suggest that murine nonspecific airway hyperresponsiveness is determined by multiple genes.     

Differential lung mechanics are genetically determined in inbred murine strains.

Genetic determinants of lung structure and function have been demonstrated by differential phenotypes among inbred mice strains. For example, previous studies have reported phenotypic variation in baseline ventilatory measurements of standard inbred murine strains as well as segregant and nonsegregant offspring of C3H/HeJ (C3) and C57BL/6J (B6) progenitors. One purpose of the present study is to test the hypothesis that a genetic basis for differential baseline breathing pattern is due to variation in lung mechanical properties. Quasi-static pressure-volume curves were performed on standard and recombinant inbred strains to explore the interactive role of lung mechanics in determination of functional baseline ventilatory outcomes. At airway pressures between 0 and 30 cmH2O, lung volumes are significantly (P < 0.01) greater in C3 mice relative to the B6 and A/J strains. In addition, the B6C3F1/J offspring demonstrate lung mechanical properties significantly (P < 0.01) different from the C3 progenitor but not distinguishable from the B6 progenitor. With the use of recombinant inbred strains derived from C3 and B6 progenitors, cosegregation analysis between inspiratory timing and measurements of lung volume and compliance indicate that strain differences in baseline breathing pattern and pressure-volume relationships are not genetically associated. Although strain differences in lung volume and compliance between C3 and B6 mice are inheritable, this study supports a dissociation between differential inspiratory time at baseline, a trait linked to a putative genomic region on mouse chromosome 3, and differential lung mechanics among C3 and B6 progenitors and their progeny.     

Variation in Genome-Wide Levels of Meiotic Recombination Is Established at the Onset of Prophase in Mammalian Males

Segregation of chromosomes during the first meiotic division relies on crossovers established during prophase. Although crossovers are strictly regulated so that at least one occurs per chromosome, individual variation in crossover levels is not uncommon. In an analysis of different inbred strains of male mice, we identified among-strain variation in the number of foci for the crossover-associated protein MLH1. We report studies of strains with “low” (CAST/EiJ), “medium” (C3H/HeJ), and “high” (C57BL/6J) genome-wide MLH1 values to define factors responsible for this variation. We utilized immunofluorescence to analyze the number and distribution of proteins that function at different stages in the recombination pathway: RAD51 and DMC1, strand invasion proteins acting shortly after double-strand break (DSB) formation, MSH4, part of the complex stabilizing double Holliday junctions, and the Bloom helicase BLM, thought to have anti-crossover activity. For each protein, we identified strain-specific differences that mirrored the results for MLH1; i.e., CAST/EiJ mice had the lowest values, C3H/HeJ mice intermediate values, and C57BL/6J mice the highest values. This indicates that differences in the numbers of DSBs (as identified by RAD51 and DMC1) are translated into differences in the number of crossovers, suggesting that variation in crossover levels is established by the time of DSB formation. However, DSBs per se are unlikely to be the primary determinant, since allelic variation for the DSB-inducing locus Spo11 resulted in differences in the numbers of DSBs but not the number of MLH1 foci. Instead, chromatin conformation appears to be a more important contributor, since analysis of synaptonemal complex length and DNA loop size also identified consistent strain-specific differences; i.e., crossover frequency increased with synaptonemal complex length and was inversely related to chromatin loop size. This indicates a relationship between recombination and chromatin compaction that may develop as DSBs form or earlier during establishment of the meiotic axis.     

The response of recombinant inbred strains of mice to bacterial lipopolysaccharides.

Fourteen recombinant inbred strains of mice have been produced by the inbreeding of the F2 generation of a cross between C57BL/6J and C3H/HeJ progenitor mice. The responses of these BXH strains to bacterial lipopolysaccharides (LPS) have been characterized. Four BXH strains are high LPS responders and nine strains are low LPS responders. One BXH strain shows intermediate responsiveness which may reflect residual heterozygosity. F1 hybrid mice from low x high responder strains were intermediate in their response to LPS suggesting additive genetic control. The LPS responses in backcross mice from the F1 x low LPS responders showed segregation consistent with LPS responsiveness being determined by a single gene. In 13/14 BXH strains, there was concordant inheritance of LPS responsiveness and the major urinary protein locus Mup-1b. The association of the expression of the Mup-1 alleles with LPS responsiveness in the BXH strains suggests that the defective LPS response gene in C3H/HeJ mice is located on chromosome 4.     

Genetic analysis of barrel field size in the first somatosensory area (SI) in inbred and recombinant inbred strains of mice

We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A /J, C57BL /6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15 +/- 0.10 mm(2), n = 7) than C57BL /6J (5.48 +/- 0.13 mm(2), n = 10), C3H/HeJ (5.37 +/- 0.16 mm(2), n = 10), and A/J mice (5.04 +/- 0.09 mm(2), n = 15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n = 4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses.     

The coupling of crossing over and homologous synapsis in maize inversions

Because fresh initiations of synapsis must occur for homologous synapsis of internal heterozygously inverted chromosome segments, attention has been directed at homologous synapsis and crossing over in overlapping paracentric inversions in the long arm of chromosome 1 of maize. In an earlier study with a relatively short inversion (where double crossovers within the inversion were rare), a recombination nodule (RN) was generally found at pachytene in reverse paired (homologously synapsed) inverted regions. Crossover frequency within the inversion, which could be independently estimated from analysis of bridge and fragment frequency at anaphase I and II, closely corresponded to crossover frequency estimated from observed RN frequency in pachytene inversion loops. These findings were consistent with the interpretation that establishment of homologous synapsis in this case is generally coupled to crossing over. This coupling suggests that there is very early commitment to the form of resolution of recombination intermediates that results in reciprocal recombination events instead of conversion only or other noncrossover events. This study examines another, larger paracentric inversion in the long arm of chromosome 1 that completely overlaps the first inversion. It is sufficiently longer than the first inversion that double crossover events are found within it with substantial frequency and interference considerations are feasible. This study confers additional insight into the interrelationships of synapsis and crossing over and the probable sequence in which the various involved processes usually occur. It raises the strong possibility that crossovers can be initiated during the alignment phase that precedes synapsis.     

Mouse serum amyloid P-component (SAP) levels controlled by a locus on chromosome 1

Recombinant inbred strains were used to demonstrate the existence of a major locus on chromosome 1, designated Sap, which controls the endogenous concentration of the mouse acute phase reactant, serum amyloid P-component (SAP). Levels of SAP were associated with alleles at the Ly-9 locus in two sets of RI strains: BXD (C57BL/6J × DBA/2) and BXH (C57BL/6J × C3H/HeJ). Low endogenous levels of SAP were present in the C57BL/6J progenitor strain and in most of the RI strains which inherited the Ly-9 ^ballele. High levels of SAP were present in the DBA/2J and C3H/HeJ progenitors and in most of the RI strains which inherited the Ly-9 ^aallele. In the BXD strains 91% of the genetic variation of SAP levels was accounted for by segregation at the Ly-9 locus while an additional 9% was attributed to genetic factors unlinked to Ly-9. In the BXH strains the percentage of genetic variation accounted for by Ly-9 segregation was reduced to 46%, while 54% was accounted for by other genetic factors. Because of background genetic variation it was not possible to detect any crossovers between Sap and Ly-9. However, in the BXD strains the linkage between Sap and Ly-9 appears to be quite close. The B6.C-H-25 ^ccongenic strain, which carries a segment of BALB/c chromosome 1 including the minor histocompatibility locus H-25 on a C57BL/6By background, had the same endogenous SAP level as the BALB/c donor strain.     

Pharmacological manipulation of the dopaminergic system affects wheel-running activity in differentially active mice

The genetic factors involved in the regulation of physical activity are not well understood. The dopamine system has been implicated in the control of voluntary locomotion and wheel running (WR) in mice and is thus a likely candidate as a genetic/biological system important to the regulation of physical activity. This study evaluated the effects of four different dopaminergic acting drugs on WR in differentially active inbred strains of mice. High active C57L/J (n=7, 3 controls, 4 experimental) and low active C3H/HeJ (n=8, 3 controls, 5 experimental) were analyzed for baseline wheel-running indices of distance (km/day), duration (mins/day), and speed (m/min) for 21 days. Experimental mice received increasing doses over four days of each of the following drugs: SKF 81297 (D1 agonist), SCH 23390 (D1 antagonist), GBR 12783 (DAT inhibitor), and AMPT (tyrosine hydroxylase inhibitor). Each drug dose response treatment was separated by three days of recovery (no drug injections). WR indices were monitored during drug treatments and during drug wash-out phases. SKF 81297 significantly reduced (p=0.0004) WR in the C57L/J mice, but did not affect WR in the C3H/HeJ mice. GBR 12783 significantly increased (p=0.0005) WR in C3H/HeJ mice, but did not affect WR in C57L/J mice. Only duration (not overall WR) was significantly reduced in C57L/J mice in response to SCH 23390 (p=0.003) and AMPT (p=0.043). SCH 23390 (p=0.44) and AMPT (p=0.98) did not significantly affect WR in C3H/HeJ mice. These results suggest that genetic differences in dopamine signaling may play a role in the WR response to dopaminergic-acting drugs in inbred strains of mice. The high activity in the C57L/J strain appears most responsive to D1-like receptor acting drugs, while in the C3H/HeJ strain, dopamine re-uptake appears to have an influence on activity level.     

Phenotypic variation resulting from a deficiency of epidermal growth factor receptor in mice is caused by extensive genetic heterogeneity that can be genetically and molecularly partitioned

The timing of lethality caused by homozygosity for a null allele of the epidermal growth factor receptor (Egfrtm1Mag) in mice is strongly dependent on genetic background. Initial attempts to genetically map background modifiers using Swiss-derived, outbred CD-1 mice were unsuccessful. To investigate the genetic architecture contributing to survival of Egfrtm1Mag homozygous embryos, the genetic variability segregating within the outbred population was partitioned by surveying viability of Egfrtm1Mag mutants using intercrosses between 129S6/SvEvTAC-Egfrtm1Mag and nine Swiss-derived, inbred strains: ALR/LtJ, ALS/LtJ, APN, APS, ICR/HaRos, NOD/LtJ, NON/LtJ, SJL/J, and SWR/J. The observations showed that these strains support varying levels of survival of Egfrtm1Mag homozygous embryos, suggesting that genetic heterogeneity within the CD-1 stock contributed to the original lack of Egfrtm1Mag modifier detection. Similar to the Swiss-derived intercrosses, nine congenic strains, derived from 129S6/SvEvTAC, AKR/J, APN, BALB/cJ, BTBR-T+ tf/tf, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ inbred backgrounds, also supported varying levels of survival of Egfrtm1Mag mutants. By intercrossing the congenic lines to create hybrid F1 embryos, different genetic backgrounds were found to have complementary modifiers. Analysis of the congenic lines argues against heterosis of outbred backgrounds contributing to Egfrtm1Mag phenotypic variability. A detailed analysis of the crosses suggests that modifiers function at three distinct stages of development. One class of modifiers supports survival of Egfrtm1Mag homozygous embryos to mid-gestation, another class supports development through the mid-gestation transition from yolk-sac to placental-derived nutrient sources, and a third class supports survival through later stages of gestation. Data from microarray analysis using RNA from wild-type and Egfrtm1Mag mutant placentas support the existence of extensive genetic heterogeneity and suggest that it can be molecularly partitioned. This method should be generally useful to partition heterogeneity contributing to other complex traits.     

Synapsis and crossing over within a paracentric inversion in the grasshopper,Camnula pellucida

A male grasshopper, Camnula pellucida (Scudder), was found to be heterozygous for a paracentric inversion occupying approximately 10% of the length of one of the two longest chromosomes. Analysis of 297 cells in pachytene revealed inversion loops, suspected inversion loops, asynapsis, and straight pairing in 1.0, 2.7, 8.4, and 87.9% of the analyzable cells, respectively. The frequency of straight pairing (87.9%) indicated a high degree of non-homologous pairing. Analysis of 603 cells in anaphase I and II, and in telophase I and II for the presence of acentric fragments and dicentric chromatid bridges indicated that crossing over within the inversion region occured in about 8% of the cells. The difference between the frequency of the observed plus suspected inversion loops in pachytene and that of the dicentric chromatid bridges and acentric fragments in anaphase I or subsequent stages was not statistically significant. The correspondence between the presence of inversion loops and crossovers within the region of the inversion is thus similar to that observed by Maguire (1966) for a short paracentric inversion in maize. The reasons for this correspondence are considered.Supported by grants GB 1585 and GB 6745 from the National Science Foundation, Washington, D.C.