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Biomedical subjects

K Fredga

Publications and source records attributed to K Fredga.

At least 19 recordsLinked to original sources

Genetic differentiation among populations of Myopus schisticolor (the wood lemming)--isozyme variation.

To investigate genetic differentiation among populations of the wood lemming Myopus schisticolor (Muridae, Rodentia) isozyme variation in 10 populations from three regions, Fennoscandia, Western and Eastern Siberia, was examined. From 20 loci examined, the two most polymorphic ones, Idh-1 and Pgi-1, were used in the complete survey. The results of hierarchical F-statistics analysis showed significant differentiation among all populations; single locus FPT values agreed well (Idh-1, FPT = 0.20; Pgi-1, FPT = 0.20). However, allele frequencies at each locus demonstrated different patterns of subdivision among populations within regions and between regions. Thus, significant values of F-statistics within (FPR = 0.10) and between (FRT = 0.10) regions were found at Idh-1. Pgi-1 showed no significant differentiation among populations within regions (FPR = 0.01). The subdivision among populations at Pgi-1 was based on differentiation between regions (FRT = 0.19). The lack of differentiation among populations within a geographical region at the Pgi-1 locus is surprising for any rodent species, and the discrepancy between single-locus patterns of subdivision seems likely to result from selection at the Pgi-1 locus.

Animals

Unusual distribution of Zfy and Zfx sequences on the sex chromosomes of the wood lemming, a species exhibiting XY sex reversal.

Sex reversal occurs naturally in the wood lemming (Myopus schisticolor) due to the presence in populations of this species of a variant (mutated) X chromosome, designated X*. Thus, X*Y animals develop into females, whereas XY animals develop into normal males. Chromosome mapping by in situ hybridization of DNA sequences homologous to the human ZFY gene localized the wood lemming Zfx sequences to region p12----p11 on both the wild-type X and the mutated X* chromosomes, at or proximal to a presumed breakpoint (Xp12) involved in the generation of the X* chromosome from the normal X, and Zfy sequences along the entire short arm of the Y chromosome. Differences between Zfx and Zfx* were readily detected by Southern blot analysis. However, both the Zfx and Zfx* genes expressed similarly sized transcripts in all adult somatic tissues investigated. Although the precise molecular difference between the Zfx and Zfx* genes is still unknown, their chromosomal location suggests that either Zfx or some other closely linked gene(s) on the X chromosome may be a major X-linked sex-determining gene, Tdx, which in the X* chromosome fails to interact properly with the Y-linked testis-determining gene, Tdy, thus causing X*Y embryos to develop into females. At least 15 copies of wood lemming Zfy sequences are distributed along the short arm of the Y chromosome. Northern hybridization analyses of adult tissues and somatic cell lines indicated that these Zfy repeats were transcriptionally inactive. Normally, 3-kb Zfy (ZFY) transcripts are readily detected in mouse and human testes, especially in the germ cells. It has therefore been postulated that expression of the Zfy (ZFY) gene may be important for spermatogenesis. Whether the lack of sufficient Zfy transcripts in the testis of the adult wood lemming has any impact on spermatogenesis in this species is still to be elucidated by further studies.

Animals

Polymorphic HSRs in chromosome 1 of the two semispecies Mus musculus musculus and M. m. domesticus have a common origin in an ancestral population.

HSRs (homogeneously staining regions) are the cytological correlates of DNA amplification. In the house mouse, Mus musculus, many populations are polymorphic for the presence or absence of HSRs on chromosome 1. In the semispecies M. m. domesticus the amplified DNA is present within one HSR, whereas in M. m. musculus chromosomes 1 with two HSRs are found. Hybridization of HSR-specific probes to Southern blots of HSR-carrying genomic DNAs from different localities and semispecies revealed similar complex band patterns. The remaining variation is restricted to sequences with a low degree of amplification. Variation is higher between semispecies than within one semispecies. It is assumed that HSRs are derived from one original amplification event and that unequal recombination is the mechanism underlying the length variation of HSRs present today in both semispecies. Evidence from G-banding and in situ hybridization shows that the two HSRs of M. m. musculus originated from a single HSR by means of a paracentric inversion, where one break-point was located within the single HSR and the second outside the HSR. As a consequence of the paracentric inversion the two HSRs of M. m. musculus are permanently linked together. Since exchange of genes between the two semispecies is restricted to a narrow hybrid zone the amplification that gave rise to the HSR most probably occurred prior to the divergence into the semispecies M. m. domesticus and M. m. musculus about 1 million years ago.

Animals

Incidence of double-band HSRs in chromosome 1 of the house mouse, Mus musculus musculus, from Oland (Sweden): a population study.

The incidence of homogeneously staining regions (HSRs) in chromosome no. 1 of Mus musculus musculus was ascertained by C-band staining on chromosomes of mice collected on the island of Oland (Sweden). A total of 157 specimens from eight localities representing three regions were analysed. Mice with enlarged chromosome no. 1, due to double-band HSRs, were found in all three regions. The overall incidence of HSR-bearing chromosomes was 6.7% in mice collected on Oland in 1988. In the two largest samples, the incidences were 14.5% (n = 31) and 3.9% (n = 76). With regard to HSR size, several different variants were present. Size differences were found for the proximal as well as for the distal HSR band. Different mutant forms were found even within one population (a single farm). The implications of these findings are discussed.

Animals

The behavior during pachynema of a normal and an inverted Y chromosome in Microtus agrestis.

The pachytene behavior of the chromosomes of Microtus agrestis (L.) (Rodentia, Arvicolidae) males carrying either the standard, or the pericentrically inverted Lund Y chromosome have been examined by electron microscopy of microspread spermatocytes. There is no synapsis between the X and either the standard or the Lund Y chromosomes during any substage of pachynema. Since synapsis is generally considered a prerequisite for crossing over, there appears to be no opportunity for crossover or chiasma formation between the X and Y in this species. The G-, C- and NOR-banded mitotic karyotypes of animals carrying the standard and Lund Y are also presented.

Animals

Absence of synapsis during pachynema of the normal sized sex chromosomes of Microtus arvalis.

The pachytene behavior of the chromosomes of males of Microtus arvalis (Pall.) (Rodentia, Arvicolidae) was examined by electron microscopy in microspread preparations of spermatocytes. There was no synapsis between the axes of these two chromosomes during this period. Since synapsis is universally considered a prerequisite for crossing over and chiasmata formation, disjunction of the sex chromosomes in this species prerequisite for crossing over and chiasmata formation, disjunction of the sex chromosomes in this species must be presumed to be achiasmatic. Unlike previously examined species with no synapsis or crossing over between the X and Y, the sex chromosomes of M. arvalis are of normal size: the X chromosome is of an "original" X size and the Y is a small acrocentric. C-band studies of M. arvalis mitotic metaphase reveal no blocks of heterochromatin on the sex chromosomes. The implications of these findings are discussed.

Animals

Aberrant chromosomal sex-determining mechanisms in mammals, with special reference to species with XY females.

Both mouse and man have the common XX/XY sex chromosome mechanism. The X chromosome is of original size (5-6% of female haploid set) and the Y is one of the smallest chromosomes of the complement. But there are species, belonging to a variety of orders, with composite sex chromosomes and multiple sex chromosome systems: XX/XY1Y2 and X1X1X2X2/X1X2Y. The original X or the Y, respectively, have been translocated on to an autosome. The sex chromosomes of these species segregate regularly at meiosis; two kinds of sperm and one kind of egg are produced and the sex ratio is the normal 1:1. Individuals with deviating sex chromosome constitutions (XXY, XYY, XO or XXX) have been found in at least 16 mammalian species other than man. The phenotypic manifestations of these deviating constitutions are briefly discussed. In the dog, pig, goat and mouse exceptional XX males and in the horse XY females attract attention. Certain rodents have complicated mechanisms for sex determination: Ellobius lutescens and Tokudaia osimensis have XO males and females. Both sexes of Microtus oregoni are gonosomic mosaics (male OY/XY, female XX/XO). The wood lemming, Myopus schisticolor, the collared lemming, Dirostonyx torquatus, and perhaps also one or two species of the genus Akodon have XX and XY females and XY males. The XX, X*X and X*Y females of Myopus and Dicrostonyx are discussed in some detail. The wood lemming has proved to be a favourable natural model for studies in sex determination, because a large variety of sex chromosome aneuploids are born relatively frequently. The dosage model for sex determination is not supported by the wood lemming data. For male development, genes on both the X and the Y chromosomes are necessary.

Animals

Chromosome analysis of human oocytes recovered from preovulatory follicles in stimulated cycles.

To investigate the incidence and types of abnormalities of chromosome number in oocytes, we recovered preovulatory oocytes from 17 women who were undergoing clomiphene stimulation and laparoscopy because of infertility. Twenty-three oocytes were recovered and studied after they had been fixed with a gradual-fixation method: 17 of the oocytes had numbers of chromosomes in the haploid range (19 to 25 second-metaphase chromosomes), 4 had only 1 to 5 chromosomes, 1 was not analyzable, and 1 had 23 chromosome bivalents in the first metaphase. Of the oocytes with chromosome numbers in the haploid range, nine had an apparently normal haploid set of 23 chromosomes. Two had 1 to 2 additional chromosomes, three lacked 2 to 4 chromosomes, and three had totals of chromosomes that were close to 23 but could not be determined with certainty. We conclude that infertile women undergoing clomiphene stimulation have a high proportion (nearly 50 percent) of oocytes with an abnormal karyotype. If this is also true of fertile women, including those not taking clomiphene, it may explain the high frequency of chromosome aberrations occurring in early spontaneous abortion and the low pregnancy rate after in vitro fertilization.

Abortion, Spontaneous

Steroid sulphatase levels are higher in males than in females of the root vole (Microtus oeconomus). Yet another rodent with an active Y-linked allele?

Steroid sulfatase (STS; EC 3.1.6.2) levels were assayed in cultured fibroblasts of root voles captured in the wild. Four independent experiments were performed using two different substrates (DHEAS and E1S). Evidence is presented that in this species, STS levels are significantly higher in males than in females (ratio 1.6:1). We discuss our findings on a comparative basis and suggest that in the root vole the STS gene(s) is X- and Y-linked (as in the mouse) and that it is subject to X-inactivation, or partially so, on one of the X chromosomes in the female.

Alleles

Chromosome analysis of human oocytes failing to cleave after insemination in vitro.

Seventy-six human oocytes lacking signs of fertilization 48 h after insemination in vitro were fixed for chromosome analysis. Only one out of 61 oocytes showed mitotic chromosomes indicating fertilization. Thus, non-cleavage is almost synonymous with non-fertilization. Chromosomes in second meiosis were found in 60 oocytes, of which 52 (86.7%) were analysable. Of these, only 18 (34.6%) displayed an apparently normal 23,X karyotype. Fifteen preparations showed no chromosomes at all but some contained small nuclei, most likely due to degeneration. An earlier stage of degeneration could be represented by a group of second meiosis oocytes (20.0%) carrying between 10 and 18 chromosomes. The large proportion of chromosome abnormalities in this sample might have been due to the fact that the oocytes were unfertilized and perhaps that abnormal oocytes had matured due to ovarian stimulation.

Adult

Ploidy in human cleavage stage embryos after fertilization in vitro.

Chromosome preparations were made from 15 cleaved human embryos in the 2- to 12-cell stage after in-vitro fertilization. All showed two pronuclei before the first cleavage. Twelve had at least one diploid metaphase, while three had interphase nuclei only. There was no evidence of parthenogenetic haploid cleavage. As expected, the frequency of metaphases increased with duration of colchicine treatment: 25 and 55% of the cells reached metaphase after 6-13 and 16-24 hours' treatment, respectively. Cleaved embryos with 'ideal' blastomere numbers (2, 4 or 8) showed a considerably higher metaphase frequency than others. For a more detailed chromosome analysis the technique will have to be further improved. The asynchronous cleavage of blastomeres makes optimal treatment by mitogens difficult.

Adult

Relationship between nucleoli and sex chromosomes during meiosis of the male wood lemming Myopus schisticolor: a fine-structure study.

Electron microscopy of ultrathin serial sections has been used to study the origin and fate of a mass of fibrillar material (FM) during spermatogenesis in the wood lemming Myopus schisticolor. In the course of early pachytene, one of the two nucleoli completely disappears. The remaining nucleolus loses its granular portion and acquires a "round body" encased by the fibrillar moiety, and the restructuring is accompanied by the appearance of FM in the close vicinity of this nucleolus. During diakinesis, the FM increases in volume and density and selectively infiltrates the chromatin of the XY pair. The intermingling of sex chromosomes and FM is at its maximum in metaphase I, giving the XY chromatin a patchy appearance. The FM separates along with the chromatin during the ensuing anaphase I and is shed from the chromosomes during early telophase I. By the time the nuclear envelope is reconstituted, the FM is completely separated from the chromatin. It disintegrates in the spermatids. The FM could not be stained using the Ag-NOR technique. In the wood lemming, X and Y chromosomes show an end-to-end association without a detectable synaptonemal complex. The FM may contribute to the attachment of the two sex chromosomes to each other. Thus, the FM is considered to be a substitute for a chiasma, which normally guarantees proper segregation in anaphase I.

Animals

Chromosome preparations in the field from mammals long after death.

Chromosome preparations of high quality can be obtained from bone marrow cells of small mammals that have been dead for 20 hr or longer. The bone marrow is rinsed out of the femurs with RPMI medium supplemented with 15% fetal calf serum. Add 0.05-0.1 ml of a 0.01% colchicine solution to 5 ml of medium-cell suspension. After 1/2-1 hr of colchicine treatment at 37 C the cells are spun down and the supernatant replaced by 5 ml of hypotonic (0.075 M) KCl. After 12 min in the hypotonic solution at 37 C the cells are fixed in methanol:acetic acid 3:1. Air dried preparations are made after repeating the fixation procedure three times and the chromosomes are stained with Giemsa, if required after pretreatment of the preparations for banding, e.g., GTG. Technical hints for field work are given. The technique has proven successful with several species of rodents and shrews.

Animals