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Biomedical subjects

K Fredga

Publications and source records attributed to K Fredga.

At least 19 recordsLinked to original sources
PubMed2004

No apparent reduction of gene flow in a hybrid zone between the West and North European karyotypic groups of the common shrew, Sorex araneus.

The common shrew, Sorex araneus, exhibits an unusually high level of karyotypic variation. Populations with identical or similar karyotypes are defined as chromosome races, which are, in turn, grouped into larger evolutionary units, karyotypic groups. Using six microsatellite markers, we investigated the genetic structure of a hybrid zone between the Sidensjö and Abisko chromosome races, representatives of two distinct karyotypic groups believed to have been separated during the last glacial maximum, the West European karyotypic group (western group) and the North European karyotypic group (northern group), respectively. Significant FST values among populations suggest some weak genetic structure. All hierarchical levels show similar levels of genetic differentiation, equivalent to levels of genetic structure in several intraracial studies of common shrew populations from central Europe. Notably, genetic differentiation was of the same order of magnitude between and within karyotypic groups. Although the genetic differentiation was weak, the correlation between genetic and geographical distance was positive and significant, suggesting that the genetic variation observed between populations is a function of geographical distance rather than racial origin. Hence, considerable chromosomal differences do not seem to prevent extensive gene flow.

Animals↗
PubMed2001

Characterization of the Xp21-23 region in the wood lemming, a region involved in XY sex reversal.

The wood lemming (Myopus schisticolor) harbors two types of X chromosome, a normal X and a variant X, designated X*. The X* chromosome contains a mutation that causes XY sex reversal. We have previously demonstrated that the Xp21-23 region is deleted from X* and is associated with XY sex reversal. To further analyze the deleted region, we have constructed and characterized seven X chromosome- and region-specific recombinant DNA libraries. Further, we have screened mouse fetal gonad cDNA libraries with the microdissected Xp21-23 DNA as a probe in an attempt to identify homologous and expressed sequences from the deletion. Fourteen positive clones were isolated, and sequence analyses showed that ten of these contained identical sequences homologous to mouse gamma-satellite sequences. One of the remaining four was perfectly homologous to the mouse gene Ccth (chaperonin containing t-complex polypeptide 1, eta subunit). Southern blot indicated that the Ccth cDNA was located on the X chromosome, not deleted from the X* but closely linked to the deletion region. Although the role of the Ccth containing region in sex determination of the wood lemming requires additional studies, the isolation of the mouse Ccth gene by the deletion Xp21-23 probe could be important since this gene is mainly expressed in testis.

Animals↗
PubMed2001

EM studies of female meiosis in wood lemmings with different sex chromosome constitutions.

The chromosomes were studied throughout meiotic prophase by electron microscopy of surface-spread oocytes from one XX, four X*X, and three X*Y female wood lemmings, Myopus schisticolor. The X* chromosome had originated from X by a deletion and an inversion in the short arm. The deletion was confirmed in pachytene cells from X*X females; a D-loop was present in the sex bivalent in 16.8% of the cells, and asynapsis of unequal ends was seen in 9.1% of other cells. At late pachytene the D-loop underwent synaptic adjustment. The breakpoints of the deletion are in G-light bands. No inversion loop was seen, which also is in agreement with Ashley's ('88) hypothesis; at least one of the presumed breakpoints of the inversion is in G-dark chromatin. Various types of synaptic abnormalities, such as nonhomologous pairing (triple pairing, interchange, self-synapsis), univalents, foldbacks, and broken lateral elements, were encountered in all types of female. X*Y females showed a high frequency of abnormal oocytes (70.7%), which significantly exceeded that of X*X (23.1%) and XX (8.1%). Univalents were particularly common in the X*Y females. J. Exp. Zool. 290:504-516, 2001.

Animals↗
PubMed2000

Gonadal development and birth weight in X*X and X*Y females of the wood lemming, Myopus schisticolor.

A quantitative histological analysis of ovaries from 8- to 10-day-old wood lemmings revealed significant differences between females with X*Y and X*X sex chromosome constitutions. The ovarian volume of X*Y females was on average 57% of X*X, and the number of oocytes was less than half in X*Y compared to X*X. However, the frequency of growing oocytes in relation to the total number was 6.5% for X*Y compared to 3.0% for X*X. Oogenesis in X*Y wood lemmings resembles in many respects that of mice heterozygous for certain translocations and with tertiary trisomy (Ts31H), and those with X0 monosomy. The fertility in X*Y wood lemmings is not reduced. On the contrary, X*Y females have a higher reproductive fitness than X*X and XX. This is discussed in relation to the present findings. The body weight at birth was 8% higher in X*Y than in X*X.

Aneuploidy↗
PubMed1999

Telomeric (TTAGGG)n sequences are associated with nucleolus organizer regions (NORs) in the wood lemming.

The distribution of the (TTAGGG)n telomeric sequence was studied in chromosomes of the wood lemming, Myopus schisticolor, by fluorescence in-situ hybridization. As expected, the hybridization signals were observed at telomeres of all chromosomes. However, quite a number of interstitial telomeric sites were present in the pericentric heterochromatic regions. Consistent strong hybridization signals were also seen at one terminus of chromosomes 5, 7 and 12--15. By post-hybridization G-banding and silver-staining, the large blocks of the telomeric sequences on chromosomes 5 and 12 were localized to nucleolus organizer regions (NORs).

Animals↗
PubMed1999

Isolation and characterization of a hantavirus from Lemmus sibiricus: evidence for host switch during hantavirus evolution.

A novel hantavirus, first detected in Siberian lemmings (Lemmus sibiricus) collected near the Topografov River in the Taymyr Peninsula, Siberia (A. Plyusnin et al., Lancet 347:1835-1836, 1996), was isolated in Vero E6 cells and in laboratory-bred Norwegian lemmings (Lemmus lemmus). The virus, named Topografov virus (TOP), was most closely related to Khabarovsk virus (KBR) and Puumala viruses (PUU). In a cross focus reduction neutralization test, anti-TOP Lemmus antisera showed titers at least fourfold higher with TOP than with other hantaviruses; however, a rabbit anti-KBR antiserum neutralized TOP and KBR at the same titer. The TOP M segment showed 77% nucleotide and 88% amino acid identity with KBR and 76% nucleotide and 82% amino acid identity with PUU. However, the homology between TOP and the KBR S segment was disproportionately higher: 88% at the nucleotide level and 96% at the amino acid level. The 3' noncoding regions of KBR and the TOP S and M segments were alignable except for 113- and 58-nucleotide deletions in KBR. The phylogenetic relationships of TOP, KBR, and PUU and their respective rodent carriers suggest that an exceptional host switch took place during the evolution of these viruses; while TOP and KBR are monophyletic, the respective rodent host species are only distantly related.

Animals↗
PubMed1998

Mediterranean Europe as an area of endemism for small mammals rather than a source for northwards postglacial colonization.

There is a general perception that central and northern Europe were colonized by range expansion from Mediterranean refugia at the end of the last glaciation. Data from various species support this scenario, but we question its universality. Our mitochondrial DNA studies on three widespread species of small mammal suggest that colonization may have occurred from glacial refugia in central Europe-western Asia. The haplotypes on the Mediterranean peninsulae are distinctive from those found elsewhere. Rather than contributing to the postglacial colonization of Europe, Mediterranean populations of widespread small mammals may represent long-term isolates undergoing allopatric speciation. This could explain the high endemism of small mammals associated with the Mediterranean peninsulae.

Animals↗
PubMed1998

XY sex reversal in the wood lemming is associated with deletion of Xp21-23 as revealed by chromosome microdissection and fluorescence in situ hybridization.

In the wood lemming (Myopus schisticolor), XY sex reversal occurs naturally because of the presence of an X chromosome variant designated X*. The two types of X chromosome, X and X*, can be distinguished by G-banding, and analyses have demonstrated complex rearrangements of the short arm of X*. Here, chromosomal microdissection, degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and fluorescence in situ hybridization (FISH) techniques have been used to generate and map DNA probes for different parts of the X and X* chromosomes. The results showed that the region of Xp21-23 is deleted from the X* and some of the deleted DNA sequences are homologous to the mouse gamma-satellite. The deletion must be associated with the sex reversal in this species. FISH experiments with dissected probes of X and distal half of Xq provided evidence for presence of homologous sequences between large regions of the X and Y chromosomes, including euchromatic and heterochromatic parts of the sex chromosomes. The findings of this study will be of significance for further cloning of important candidate gene(s) responsible for the XY sex reversal.

Animals↗
PubMed1998

Spermatogenesis in common shrews, Sorex araneus, from a hybrid zone with extensive Robertsonian polymorphism.

The analysis of the fertility of hybrid and nonhybrid individuals from a chromosomal contact zone gives us the possibility of studying the role of chromosomes in speciation processes. In this study, homozygous, "simple" and "complex" Robertsonian heterozygous male common shrews (Sorex araneus) from the Abisko-Sidensjö chromosomal hybrid zone in Sweden were analysed. The degree of germ cell death was estimated, sperm counts were performed and the testis and seminal vesicles weighed in each individual. Chromosome interactions and synapsis at pachytene were examined under the EM. The weight of the testis was significantly different in the three karyotypic groups and "complex" heterozygotes suffered higher germ cell death than homozygotes and "simple" heterozygotes. Interactions between chromosomes at pachytene were rare. Nonhomologous pairing in the centromeric regions of autosomal trivalents (side arms) was common while asynapsed segments were seldom found. Thus, the difference in the reproductive characteristics of the common shrew might be due to genetic factors rather than Robertsonian translocations.

Animals↗
PubMed1997

The origin and distribution of the Lund Y chromosome in Microtus agrestis (Rodentia, Mammalia).

The Lund Y (Lu-Y) chromosome of the field vole (Microtus agrestis) is distinguished from the standard Y (St-Y) by its much longer short arm. G-banding revealed that the Lu-Y originated by a pericentric inversion in the St-Y. Chromosome analysis of 297 male field voles from 92 localities in Fennoscandia. Germany, and England, in addition to data from the literature, made it possible to map the distribution area of the Lu-Y. It is restricted to the south-western parts of Sweden. The question of when and where the Lund Y population originated is discussed. Adding data from a hybrid zone (Jaarola et al. 1997) and from females, totally 491 specimens from 120 localities were analyzed without detecting any variation in chromosome number and autosome morphology. Other cases of intraspecific Y chromosome polymorphism in mammals, and the use of Y chromosome variants as population genetic markers, are discussed.

Animals↗
PubMed1997

Meiosis and fertility in common shrews, Sorex araneus, from a chromosomal hybrid zone in central Sweden.

Adult male common shrews from the Uppsala and Hällefors Robertsonian chromosomal races and hybrids were collected from the area of Surahammar in Sweden. Meiosis and fertility of hybrid (complex heterozygotes) and nonhybrid (homozygotes) individuals were compared based on an analysis of chromosomal interactions and synapsis at pachytene, chiasma characteristics at diakinesis, and germ-cell death. No individuals suffered severe germ-cell loss, and the differences found among the Uppsala and Hällefors homozygotes and the hybrids were not significant. In complex heterozygotes, ring configurations of four elements were observed at meiosis I, with one chiasma per chromosome arm. Abnormal rings were frequent at pachytene, but interactions between the ring and other chromosomes were seldom found. There is no indication from this study of a differential fertility between homozygotes and ring IV-forming complex heterozygotes in males.

Animals↗
PubMed1995

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↗
PubMed1994

The curious normality of the synaptic association between the sex chromosomes of two arvicoline rodents: Microtus oeconomus and Clethrionomys glareolus.

In all eight species of arvicoline (microtine) rodents previously described, the X and Y chromosomes have remained asynaptic throughout pachynema. Since synapsis is presumed to be a prerequisite for crossing over, it has been concluded that the sex chromosomes in these species are also achiasmatic, but the mechanism(s) of their disjunction remains an enigma. Their asynaptic, achiasmatic condition has been attributed to loss of the pseudoautosomal region (Borodin et al. 1991; Carnero et al. 1991; Jiménez et al. 1991). This loss has been postulated to include all arvicoline rodents. We describe here the sex chromosome behavior during meiotic prophase of two additional species in this group: Microtus oeconomus and Clethrionomys glareolus. In both species there is extensive synapsis between the X and Y, providing the usual opportunity for XY recombination. These findings challenge the concept of the pseudoautosomal region as an evolutionarily conserved region of homology, at least within the arvicoline rodents. The unexpected finding of synapsis in two very different species, one with a derived and one with a primitive karyotype is discussed within its phylogenetic context.

Animals↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1989

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↗