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Chromosome segregation at meiosis I in female T(2;4)1Gö/+ mice: no evidence for a decreased crossover frequency with maternal age.

The influence of age and hormones on chromosome segregation at meiosis I was studied in female mice heterozygous for the T(2;4)1Gö translocation. Females of two age groups (18-22 and 40-56 weeks old) were stimulated for ovulation with different doses of gonadotropins (1.5 IU PMS/1.0 IU HCG or 10 IU PMS/10 IU HCG). Analysis of metaphase II oocytes revealed the highest level of hyperhaploidy (1.8%) and presegregation (4.4%) in the young females receiving the low dose. Presegregation preferentially affected the small 4(2) marker chromosome. There was no significant interference of the tetravalent with disjunction of the nontranslocated normal bivalents. Moreover, no remarkable difference in the mode of segregation (adjacent I, II or alternate) was observed. Recombination within the interstitial pairing segments of the chromosomes involved in the translocation allowed us to calculate cross-over frequencies in ovulated oocytes. For both the large 2(4) and the small 4(2) marker chromosomes, this frequency was higher in old than in young T(2;4)1Gö/+ females. Our data do not support the production line hypothesis of Henderson and Edwards (1968) which claims that chiasma frequency in oocytes decreases with maternal age.

Aging

Partial exclusion of the Nocardia erythropolis chromosome in nocardial recombinants.

Segregation of genes specifying nutritional requirements and inhibitor resistance was analyzed in recombinants from crosses of Nocardia erythropolis with N. canicruria. With all employed characters as both selecting and nonselecting markers, a single linear linkage group was depicted with genes in the following order; leu-6 gly-4 purB2 tetA9 his-1 eryA7 strB2 ser-1 arg-1. The relative frequency of crossovers between gene pairs was found to decrease as the map is read from leu-6 to the right. The phenotype for arg-1 was found infrequently in recombinants. This fact, coupled with the observed decrease in crossover frequency dependent upon map position, suggested two alternative explanations to account for the observed results. (i) Zygote formation among these nocardiae is a consequence of partial, oriented chromosome transfer from N. erythropolis to N. canicruria and is similar to the mechanism of polar transfer reported in matings of Hfr by F(-)Escherichia coli. (ii) Being of diverse origin, the chromosomes of N. erythropolis and N. canicruria are not completely homologous, and decrease in crossover frequency dependent upon map position results from such chromosomal heterology. In this hypothesis, the infrequent occurrence of arg-1 among recombinants is considered to be an artifact resulting from the action of a previously unrecognized suppressor gene for arg-1 present in N. canicruria.

Chromosome Mapping

Substantial non-homologous recombination and structural variation results from Brassica AABC and CCAB hybrid meiosis.

Meiotic crossovers contribute to genetic diversity and play a crucial role in homologous chromosome segregation. Non-homologous crossovers in Brassica, involving the exchange of genetic material between genomes, can be valuable for transferring novel traits or characteristics between Brassica species. However, there are a limited number of studies that specifically investigate crossover frequencies in populations of interspecific hybrids. We investigated the distribution and frequency of homologous crossover events, as well as non-homologous recombination and structural variation, in hybrids between B. juncea (AABB) × B. napus (AACC) (resulting in AABC hybrids; 5 genotypes) and B. napus (AACC) × B. carinata (BBCC) (resulting in CCAB hybrids; 4 genotypes). The analysis was performed on individuals derived from microspore culture of both unreduced and reduced gametes produced by the AABC and CCAB hybrids. All AABC and almost all CCAB unreduced gamete-derived individuals and most AABC and CCAB reduced gamete-derived individuals showed copy number variation indicative of non-homologous (A-C) recombination. Additionally, a higher frequency of homologous crossovers, also in centromeric and pericentromic regions, was observed in the diploid genomes of the AABC and CCAB hybrids. Overall, these hybrid types show high frequencies of A-C introgressions, which may be useful in B. juncea or B. carinata introgression breeding, and this increased recombination frequency may help break up existing linkage disequilibrium blocks in the Brassica A and C genomes.

Meiosis

The pattern of pairing that is effective for crossing over in complex B-A chromosome rearrangements in maize. III. Possible evidence for pairing centers.

The study of the mechanism of meiotic homolog pairing, approached by comparing chiasma frequencies in rearranged segments that differ in relative length and intrachromosomal location, is substantially extended here. For the first time, two kinds of evidence were found that centers specialized for alignment pairing may exist in maize chromosomes: for two segments, higher than average crossover frequency per unit length was maintained when these were located in several different chromosomal positions with respect to centromere and telomere, and in fact apart from their own normal centromeres and telomeres. High crossover frequencies in these segments regardless of position are considered to reflect innate capacity for alignment pairing due to relatively strong pairing center content. For a short rearranged segment, chiasma frequency was drastically reduced, and evidence suggests that all of the chiasmata found there depended upon juxtaposition made possible by the completion of the zip-up pairing process in the other arms of the translocation configuration. This short segment is thought to be essentially devoid of pairing center content. It seems possible that crossover frequency depression in short rearranged segments may usually not be due, as commonly supposed, to mechanical difficulties inherent in formation of contorted configurations, but rather to absence of pairing centers within them and the relative rarity (compared to the normal sequence situation) of enabling zip-up pairing. Evidence also indicates that pairing which leads to crossing over must frequently occur between internal translocated segments and their normal sequence counterparts in a way which cannot be dependent upon zipping-up of two-by-two pairing initiated at or near telomeres. Pairing centers in maize are probably numerous and widely dispersed, since coarse direct proportionality is found when chiasma frequency is compared for an array of segment lengths.

Centromere

A linkage map of mouse chromosome 1 using an interspecific cross segregating for the gld autoimmunity mutation.

An interspecific backcross was used to define a high resolution linkage map of mouse Chromosome (Chr) 1 and to analyze the segregation of the generalized lymphoproliferative disease (gld) mutation. Mice homozygous for gld have multiple features of autoimmune disease. Analysis of up to 428 progeny from the backcross [(C3H/HeJ-gld x Mus spretus)F1 x C3H/HeJ-gld] established a map that spans 77.6 cM and includes 56 markers distributed over 34 ordered genetic loci. The gld mutation was mapped to a less than 1 cM segment on distal mouse Chr 1 using 357 gld phenotype-positive backcross mice. A second backcross, between the laboratory strains C57BL/6J and SWR/J, was examined to compare recombination frequency between selected markers on mouse Chr 1. Significant differences in crossover frequency were demonstrated between the interspecific backcross and the inbred laboratory cross for the entire interval studied. Sex difference in meiotic crossover frequency was also significant in the laboratory mouse cross. Two linkage groups known to be conserved between segments of mouse Chr 1 and the long arm of human Chrs 1 and 2 where further defined and a new conserved linkage group was identified that includes markers of distal mouse Chr 1 and human Chr 1, bands q32 to q42.

Animals

A frequency importance function for continuous discourse.

Normal hearing subjects estimated the intelligibility of continuous discourse (CD) passages spoken by three talkers (two male and one female) under 135 conditions of filtering and signal-to-noise ratio. The relationship between the intelligibility of CD and the articulation index (the transfer function) was different from any found in ANSI S3.5-1969. Also, the lower frequencies were found to be relatively more important for the intelligibility of CD than for identification of nonsense syllables and other types of speech for which data are available except for synthetic sentences [Speaks, J. Speech Hear. Res. 10, 289-298 (1967)]. The frequency which divides the auditory spectrum into two equally important halves (the crossover frequency) was found to be about 0.5 oct lower for the CD used in this study than the crossover frequency for male talkers of nonsense syllables found in ANSI S3.5-1969 and about 0.7 oct lower than the one for combined male and female talkers of nonsense syllables reported by French and Steinberg [J. Acoust. Soc. Am. 19, 90-119 (1947)].

Adolescent

Programmable hearing aid with multichannel compression.

A portable programmable hearing aid with multichannel compression was constructed with three channels with two independently variable crossover frequencies. The compression knee-point and attenuation in each channel and the two crossover frequencies can be programmed from a separate programming unit. Speech discrimination for seven subjects with sensorineural hearing loss was evaluated, comparing each subject individually in three different cases--equalization, multichannel compression and the subject's own conventional hearing aid. Each subject wore each aid for about a week in his/her own environment and was then tested. The following speech discrimination tests were used: monosyllabic phonetically balanced words with and without background noise, nonsense syllables in quiet, and a constant test in quiet and in noise. The study showed that some patients with sensorineural hearing loss accompanied by recruitment can double their speech discrimination by using a hearing aid with multichannel compression.

Hearing Aids

The temporal sequence of synaptic initiation, crossing over and synaptic completion.

Questions are raised as to the validity of arguments that crossover positions have been demonstrated to be normally established only during pachytene (after synapsis is maximal). An alternative and testable hypothesis is that crossover commitment can occur at events of synaptic initiation.-Measurements are presented of extents of pachytene synapsis and failure in and around a region of maize chromosome heterozygous for a short paracentric inversion, and these are compared to conjectured expectations from observations of crossover frequencies within the inversion. Various hypotheses consistent with the results are considered. It is pointed out that the hypothesis that increases in crossover frequency in the synapsed region of the inversion are compensatory to crossover inhibitions elsewhere requires complex assumptions: that the adjustment must take place among, not within cells and that the enhancement is preferentially expressed within the inversion instead of elsewhere in the genome. The hypothesis that the fixing and squashing procedure forces apart non-crossover regions previously synapsed but lacking a crossover also requires complex assumptions. The simplest hypothesis proposes that crossover commitment may determine synaptic expression. A role of the synaptonemal complex in the establishment of crossover sites is questioned or minimized.-Evidence is also presented with respect to conceivable function of the telomere in synaptic initiation. Restrictions on such a function, if it exists, seem to be required to account for the observations.

Chromosome Aberrations

Temporal tuning and nonlinearity of intraretinal pathways in turtle: effects of temperature, stimulus intensity, and size.

Flash responses, amplitude and phase transfer functions, and nonlinearities were measured in turtle retina for pathways with photoreceptor inputs and outputs from horizontal (HC), hyperpolarizing bipolar (HBC), sustained amacrine (AC), and on-off ganglion (GC) cells. Flash responses slowed and attenuated in all cells as temperature decreased. White-noise transfer properties of sustained-type cells (HC, HBC, AC) were of low- or bandpass type; high-frequency cut-off (fc) and phase crossover frequency decreased with temperature. fc increased as spot diameter was increased. Nonlinearity of these sustained-response pathways (distortion product frequencies in response to a sum-of-sinusoids input probe) increases with intensity and may depend on amplitude saturation limiting. On/off GC synaptic and spike activity increased as spot diameter decreased and intensity increased. Amplitude transfer functions had a low-frequency peak (PSP activity) and monotonically decreasing amplitude vs. frequency shape (spikes and transient PSP activity). Nonlinearity increased with stimulus intensity; it was maximal with 1 mm spot size, less with smaller (500 micron) and larger (5 mm) spots. It may depend on the functional equivalent of full-wave rectification (on-off response).

Animals

Proximity of the Mep-1 gene to H-2D on chromosome 17 in mice.

The Mep-1 gene on chromosome 17 in mice controls the activity of meprin, a kidney brush border metalloendopeptidase. Most inbred mouse strains of the k haplotype (e.g., CBA, C3H, AKR) are markedly deficient in meprin activity; these mice carry the Mep-1b allele. Mouse strains in which meprin activity levels are normal are designated Mep-1a. Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene. To further study the relationship between the major histocompatibility complex and Mep-1, a linkage study was conducted. Mep-1a F1 hybrids [C3H.A (KkDd) X C3H.OH (KdDk)] were backcrossed with Mep-1b C3H.OH (KdDk) parents. The progeny were assayed for H-2D markers, Pgk-2 isozymes, and meprin activity. Recombination between H-2D and Mep-1 occurred in 6 out of 284 mice, a crossover frequency of 2.1%. Mep-1 is therefore 2.1 crossover units telomeric to H-2D and approximately 0.6 crossover units from Tla. The Mep-1 locus provides a new genetic marker for the future mapping of this important area of the mouse genome.

Amino Acids, Sulfur

Frequency characteristics of the saccadic eye movement.

Using a piecewise linear approach, individual saccadic eye movements have been Fourier decomposed in an attempt to determine the effect of saccadic amplitude on frequency characteristics. These characteristics were plotted in the traditional Bode plot form, showing gain and phase as a function of frequency for various eye movement amplitudes. Up to about one octave beyond the -3 db gain frequency, the limiting system dynamics represented by the saccadic trajectory of a given amplitude may be considered linear and second order. The -3 db gain frequency was used as a measure of bandwidth, and the -90 degrees phase crossover frequency was used as a measure of undamped natural frequency. These two quantities were used to calculate the damping factor. Both bandwidth and undamped natural frequency decrease with increasing saccadic eye movement amplitude. The damping factor shows no trend with amplitude and indicates approximate critical damping. When compared with the normal variation of characteristics for a given movement, the frequency characteristics of fixed-amplitude saccades showed no generalized trends with changes in direction or DC operating level of movement.

Analog-Digital Conversion

Evaluation of a dual-channel full dynamic range compression system for people with sensorineural hearing loss.

This article describes an evaluation of an in the ear hearing aid, which applies fast-acting full dynamic range compression independently in two frequency bands. This can compensate for the loudness recruitment typically associated with sensorineural hearing loss. The crossover frequency between the two bands and the gain and compression ratio in each band are programmable to suit the individual patient. Twenty subjects with moderate sensorineural hearing loss were tested in a counterbalanced order using the aid programmed as a linear amplifier (condition L) and as a two-band compressor (condition C). All subjects were fitted binaurally. Subjects were also tested without hearing aids (condition U) and using the hearing aids that they normally wore (condition Own). Speech intelligibility was measured in quiet at three sound levels (50, 65, and 80 dB SPL), and speech reception thresholds (SRTs) in 12-talker babble were measured under monaurally and binaurally aided conditions, with the speech and babble both coincident and spatially separated. In condition C, speech intelligibility in quiet was high at all sound levels. Speech intelligibility at the two lower levels decreased in condition L, and decreased still further in conditions Own and U. Condition C gave, on average, better speech intelligibility in babble (lower SRTs) than conditions L, Own, or U. The advantage of condition C over condition L varied across subjects and was correlated with the dynamic range for tones at high frequencies; small dynamic ranges were associated with greater benefit from compression. A significant advantage for binaural aiding was found both when the speech and noise were spatially separated and when they were coincident. The binaural advantage was similar for the C and L conditions, indicating that the independent compression at the two ears did not adversely affect the use of binaural cues. Questionnaires on the subjects' experiences with the aids in everyday life indicated that they generally preferred condition C over condition L.

Adult

A mathematical model of interference for use in constructing linkage maps from tetrad data.

In determining genetic map distances it is necessary to infer crossover frequencies from the ratios of recombinant and parental progeny. To do this accurately, in intervals where multiple crossovers may occur, a mathematical model of chiasma interference must be assumed when mapping in organisms displaying such interference. In Saccharomyces cerevisiae the model most frequently used is that of R.W. Barratt. An alternative to this model is presented. This new model is implemented using a microcomputer and standard numerical methods. It is demonstrated to fit ranked tetrad data from Saccharomyces more closely than the Barratt model and thus generates more accurate estimates of map distances when used with two-point data. A computer program implementing the model has been developed for use in calculating map distances from tetrad data in Saccharomyces.

Chromosome Mapping

Evidence for different types of mechanoreceptors from measurements of the psychophysical threshold for vibrations under different stimulation conditions.

The shape of the psychophysical frequency threshold curve for vibrations presented to the skin in the frequency region 5-1000 Hz is strongly dependent on the static force that the vibrator exerts on the skin and on whether there is a rigid surround around the vibrating contactor (presence of contrast). Where there is no rigid surround, an increase in static force reduces the threshold in the high-frequency region and increases it at low frequencies. When the static forces are sufficiently large, the thresholds reach a minimum value above 30 Hz and a maximum one below 30 Hz, this being the crossover frequency. Under these conditions in the frequency region around 200 Hz, where the threshold is determined by the Pacini receptor system, the vibration sensitivities of finger pad and thenar eminence (glabrous skin) are equal, while the value for the inner side of the forearm (hairy skin) is 12 dB higher. However, when a rigid surround is used, the threshold increases above 30 Hz and decreases below 30 Hz. The latter increase in sensitivity, which is introduced by the presence of contrast cues, amounts to about 20 dB and is sharply tuned at 18 Hz for the glabrous skin of the finger. It is argued that in this case the threshold is determined by the Meissner receptor system. This increase in sensitivity is less pronounced (about 10 dB) and less sharply tuned for the other sites. Finally, when the contact of the vibrating surface to the skin is at a minimum, the vibration threshold has the same displacement value (about 3 microns) over the whole frequency region independent of the site of stimulation and whether or not a rigid surround is present.

Humans

A primary genetic map of the pericentromeric region of the human X chromosome.

We report a genetic linkage map of the pericentromeric region of the human X chromosome, extending from Xp11 to Xq13. Genetic analysis with five polymorphic markers, including centromeric alpha satellite DNA, spanned a distance of approximately 38 cM. Significant lod scores were obtained with linkage analysis in 26 families from the Centre d'Etude du Polymorphisme Humain, establishing estimates of genetic distances between these markers and across the centromere. Physical mapping experiments, using a panel of somatic cell hybrids segregating portions of the X chromosome due to translocations or deletions, are in agreement with the multilocus linkage analysis and indicate the order Xp11 . . . DXS7(L1.28)-TIMP- DXZ1(alpha satellite, cen)- DXS159(cpX73)-PGK1 . . . Xq13. The frequency of recombination in the two approximately 20-cM intervals flanking alpha satellite on either chromosome arm was roughly proportional to the estimated physical distance between markers; no evidence for a reduced crossover frequency was found in the intervals adjacent to the centromere. However, significant interfamilial variations in recombination rates were noted in this region. This primary map should be useful both as a foundation for a higher resolution centromere-based linkage map of the X chromosome and in the localization of genes to the pericentromeric region.

Alleles

Analysis of HLA-DP in HLA-DR/GLO recombinant families and in the population of south-western France.

The existing estimates of the recombination fraction between DR and DP are quite variable and often based on anecdotal observations. We have estimated the DR/DP crossover frequency on the basis of families typed for HLA markers and GLO. The frequency of DR/GLO crossing over was 8.7% (23/264 informative meioses), maternal recombinations being about twice as frequent as paternal ones. Of 17 DR/GLO recombinant families typed for DPw1-6, DP was informative in 11 (13 recombinations) but only one of these gave rise to a DR/DP crossover. According to these data the DR/DP recombination fraction is below 1%, in contrast to some earlier published materials. HLA-DR/DP haplotypic associations on 127 informative Caucasoid haplotypes have been evaluated. In agreement with previous studies, DR3 was positively associated with DPw1 and, in addition, DR7 was found to be positively associated with DP-blank (not DPw1-6). The rare DPw6 allele is possibly associated with the DR4, Dw14 allele. The DR-DP haplotype profiles suggest other associations which might become significant if larger materials are tested. The frequency of DP alleles in a random material (N = 201) was found to be in accordance with most of the previously published frequences on European Caucasoids with DPw4 as the predominating frequency (gene frequency 40%) and a blank frequency of 27%.

Alleles

Dominant enhancer effect of the meiotic mei4 mutant on recombination frequencies restricted to linkage group VI in Podospora anserina.

A mutant which increases second division segregation (SDS) frequency of locus 110 (linkage group VI) was isolated. It was called mei4 because of its meiotic deficiency. The present paper deals with its effect on meiotic recombination when heterozygous. mei4 then only acts on linkage group VI. The SDS frequencies were increased for all markers used, except locus 5 located very close to the centromere. This quasi general enhancement results exclusively in an enlargement of map distance on linkage group VI's proximal part. Crosses involving three mutant genes allowed to check that the distances on the distal part were constant. This is due to a real lack of crossover frequency modification in this region and not to a change ofchiasma interference. Among the seven linkage groups of Podospora anserina, group VI exhibits several other particularities concerning meiotic recombination, especially a lower positive chiasma interference and a more regular crossover distribution, suggesting a particular recombination regulation.

Ascomycota