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At least 865 records · Page 48Linked to original sources
PubMed1984

The cohesive population genetics of molecular drive.

The long-term population genetics of multigene families is influenced by several biased and unbiased mechanisms of nonreciprocal exchanges (gene conversion, unequal exchanges, transposition) between member genes, often distributed on several chromosomes. These mechanisms cause fluctuations in the copy number of variant genes in an individual and lead to a gradual replacement of an original family of n genes (A) in N number of individuals by a variant gene (a). The process for spreading a variant gene through a family and through a population is called molecular drive. Consideration of the known slow rates of nonreciprocal exchanges predicts that the population variance in the copy number of gene a per individual is small at any given generation during molecular drive. Genotypes at a given generation are expected only to range over a small section of all possible genotypes from one extreme (n number of A) to the other (n number of a). A theory is developed for estimating the size of the population variance by using the concept of identity coefficients. In particular, the variance in the course of spreading of a single mutant gene of a multigene family was investigated in detail, and the theory of identity coefficients at the state of steady decay of genetic variability proved to be useful. Monte Carlo simulations and numerical analysis based on realistic rates of exchange in families of known size reveal the correctness of the theoretical prediction and also assess the effect of bias in turnover. The population dynamics of molecular drive in gradually increasing the mean copy number of a variant gene without the generation of a large variance (population cohesion) is of significance regarding potential interactions between natural selection and molecular drive.

Biological Evolution↗
PubMedDate not supplied

Complete rRNA gene sequences reveal that the microsporidium Nosema bombi infects diverse bumblebee (Bombus spp.) hosts and contains multiple polymorphic sites.

Characterisation of microsporidian species and differentiation among genetic variants of the same species has typically relied on ribosomal RNA (rRNA) gene sequences. We characterised the entire rRNA gene of a microsporidium from 11 isolates representing eight different European bumblebee (Bombus) species. We demonstrate that the microsporidium Nosema bombi infected all hosts that originated from a wide geographic area. A total of 16 variable sites (all single nucleotid polymorphisms (SNPs)) was detected in the small subunit (SSU) rRNA gene and 42 (39 SNPs and 3 indels) in the large subunit (LSU) rRNA sequence. Direct sequencing of PCR-amplified DNA products of the internal transcribed spacer (ITS) region revealed identical sequences in all isolates. In contrast, ITS fragment length determined by PAGE and sequencing of cloned amplicons gave better resolution of sequences and revealed multiple SNPs across isolates and two fragment sizes in each isolate (six short and seven long amplicon variants). Genetic variants were not unique to individual host species. Moreover, two or more sequence variants were obtained from individual bumblebee hosts, suggesting the existence of multiple, variable copies of rRNA in the same microsporidium, and contrary to that expected for a class of multi-gene family under concerted evolution theory. Our data on within-genome rRNA variability call into question the usefulness of rRNA sequences to characterise intraspecific genetic variants in the Microsporidia and other groups of unicellular organisms.

Animals↗
PubMed2002

5' flanking variants of resistin are associated with obesity.

Diabetes and obesity have long been known to be related. The recently characterized adipocyte hormone resistin (also called FIZZ3/ADSF) has been implicated as a molecular link between impaired glucose tolerance (IGT) and obesity in mice. A search for sequence variants at the human resistin locus identified nine single-nucleotide polymorphisms (SNPs) but no coding variants. An investigation into the association of these SNPs with diabetes and obesity revealed two 5' flanking variants (g.-537 and g.-420), in strong linkage disequilibrium, that are associated with BMI. In nondiabetic individuals from the Quebec City area and the Saguenay-Lac-St-Jean region of Quebec, the g.-537 mutation (allelic frequency = 0.04) was significantly associated with an increase in BMI (P = 0.03 and P = 0.01, respectively). When the data from these two populations were combined and adjusted for age and sex, both the g.-537 (odds ratio [OR] 2.72, 95% CI 1.28-5.81) and the g.-420 variants (1.58, 1.06-2.35) were associated with an increased risk for a BMI > or =30 kg/m(2). In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples.

5' Untranslated Regions↗
PubMed1990

Cortical tremor: a variant of cortical reflex myoclonus.

Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

Aged↗
PubMed1996

A new variant of the viral haemorrhagic disease of rabbits virus.

A new variant of viral haemorrhagic disease of rabbits (VHD) virus, recently detected in Poland and called Blaszki (BLA), gives positive results in enzyme-linked immunosorbent assay (ELISA) and exhibits viral protein of 60 kilodaltons (VP 60), as detected by Western blot analysis. This BLA variant of VHD virus has caused high morbidity and mortality in rabbits, as have other reported variants with similar clinical signs and pathological lesions, but-in contrast to other variants-the BLA variant gave negative results in the haemagglutination test. This development indicates the limitations of haemagglutination testing in the diagnosis of VHD.

Animals↗
PubMed1990

Three genes under different developmental control encode elongation factor 1-alpha in Xenopus laevis.

We have cloned cDNAs encoding two variants of the elongation factor for protein synthesis in Xenopus laevis, called EF-1 alpha. One of these (42Sp50) is expressed exclusively in immature oocytes. It is one of two protein components of a 42S RNP particle that is very abundant in previtellogenic oocytes. The 42S RNP particle consists of various tRNAs, 5S RNA, 42Sp50 and a 5S RNA binding protein (42Sp43). A major function served by 42Sp50 appears to be the storage of tRNAs for later use in oogenesis and early embryogenesis. The second EF-1 alpha variant (EF-1 alpha O) is expressed mainly in oocytes but transiently in early embryogenesis as well. Its mRNA cannot be detected after neurulation in somatic cells. EF-1 alpha O is closely related to a third EF-1 alpha (EF-1 alpha S), discovered originally by Krieg et al. (1). EF-1 alpha S is expressed at low levels in oocytes but actively in somatic cells. The latter two proteins are very similar to known eukaryotic EF-1 alpha from other organisms and presumably function in their respective cell types to support protein synthesis.

Amino Acid Sequence↗
PubMed1975

Serum lipoprotein composition in different types of hyperlipoproteinemia.

Fasting serum lipoproteins (LP) were separated into VLDL, LDL and HDL by ultracentrifugation and the content of cholesterol and triglycerides analyzed in each LP class in 69 consecutive men attending a lipid clinic. The effect of using different cut off points in the definition of HLP was discussed. It was pointed out that by using lower values for the cut off points there is only an increase in the number of subjects with hyperlipoproteinemia (HLP) but also shifts in the proportions between the various types of HLP, particularly with increase in the amount of types IIB and IV. In addition to the LP abnormalities inherent in the definition of each type of HLP other LP abnormalities were observed. Thus type IIA HLP had cholesterol rich VLDL with an increased ratio cholesterol/triglycerides. The types of HLP with increased VLDL triglycerides had characteristic changes in both LDL and HDL. For LDL its triglyceride content was increased and HDL showed a lowering of its cholesterol content and a rise in triglycerides. These changes were more pronounced the higher the VLDL triglyceride concentration was. Both normo- and hyperlipoproteinemic subjects having the second pre-beta LP on agarose gel electrophoresis of the VLDL fraction called LPB (Late Pre Beta) had two characteristic LP features. VLDL had an increased cholesterol/triglyceride ratio. LDL had a raised triglyceride content. The relation of LPB to so called intermediary particles was discussed. When the SPB (Sinking Pre Beta) LP variant was present this had negligible effects on the LP composition. Type IIA was present in 14 percent of the 609 men. None had tendinous xanthomata. The LP pattern of this common type IIA was compared to the LP pattern of the uncommon type IIA where tendinous xanthomata are present, called IIA-X. Type IIA-X had much higher LDL cholesterol and in relation to the triglyceride content a more cholesterol rich LDL. Furthermore type IIA-X had lower VLDL lipids than the common type IIA, but type IIA-X was more cholesterol rich. The differences in clinical appearance as well as in quantitative and qualitative LP composition between the common type IIA and type IIA-X makes it important to separate these two types of HLP from each other.

Cholesterol↗
PubMed2001

Initiation of biofilm formation by Pseudomonas aeruginosa 57RP correlates with emergence of hyperpiliated and highly adherent phenotypic variants deficient in swimming, swarming, and twitching motilities.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium capable of forming biofilms on surfaces as a survival strategy. It exhibits a large variety of competition/virulence factors, such as three types of motilities: flagellum-mediated swimming, flagellum-mediated swarming, and type IV pilus-mediated twitching. A strategy frequently used by bacteria to survive changing environmental conditions is to create a phenotypically heterogeneous population by a mechanism called phase variation. In this report, we describe the characterization of phenotypic variants forming small, rough colonies that spontaneously emerged when P. aeruginosa 57RP was cultivated as a biofilm or in static liquid cultures. These small-colony (S) variants produced abundant type IV fimbriae, displayed defective swimming, swarming, and twitching motilities, and were impaired in chemotaxis. They also autoaggregated in liquid cultures and rapidly initiated the formation of strongly adherent biofilms. In contrast, the large-colony variant (parent form) was poorly adherent, homogeneously dispersed in liquid cultures, and produced scant polar fimbriae. Further analysis of the S variants demonstrated differences in a variety of other phenotypic traits, including increased production of pyocyanin and pyoverdine and reduced elastase activity. Under appropriate growth conditions, cells of each phenotype switched to the other phenotype at a fairly high frequency. We conclude that these S variants resulted from phase variation and were selectively enriched when P. aeruginosa 57RP was grown as a biofilm or in static liquid cultures. We propose that phase variation ensures the prior presence of phenotypic forms well adapted to initiate the formation of a biofilm as soon as environmental conditions are favorable.

Alginates↗
PubMed1987

Verrucous acanthosis--so-called verrucous carcinoma--of the esophagus.

Verrucous carcinoma of the esophagus is a rare variant of squamous cell carcinoma with a slow, non-invasive growth without formation of metastases. Until today, only 8 cases of verrucous carcinoma of the esophagus have been reported in the literature. All of these tumours showed infiltration of adjacent mediastinal structures or even lymph node metastases. In therefore seems doubtful, wether these tumours were really verrucous carcinomas rather than squamous cell carcinomas of the papillary type. Several authors have questioned the malignant nature of these tumors recently. We report a case of a verrucous lesion of the esophagus the course of which we were able to observe over a period of several years. Transhiatal esophagectomy without thoracotomy is recommended as treatment of choice for verrucous tumours of the esophagus.

Carcinoma, Papillary↗
PubMed1995

[Clinical variants of pseudotumor cerebri syndrome].

Increased cerebrospinal fluid pressure of usually unknown etiology is called pseudotumor cerebri. The key symptoms are headache, papilledema and fluctuating visual disturbances. Six cases are presented to illustrate the clinical variability of this syndrome. Headache or papilledema may be missing in individual cases. The clinical diagnosis can be facilitated by the recognition of accessory signs and symptoms, such as VIth nerve palsy, tinnitus and other cranial nerve disorders or neck stiffness. For the therapeutic outcome it is essential to detect and monitor visual disturbances early in the course of the disease.

Adult↗
PubMed2005

Mutation analysis of the GJB2 (connexin 26) gene in Egypt.

Fifty to eighty percent of autosomal recessive deafness is due to mutations in the GJB2 gene encoding connexin 26. Among Caucasians, the c.35delG mutation in this gene accounts for up to 30 to 70% of all cases with early childhood deafness. In this study, we present the analysis of the GJB2 gene in 159 Egyptians from 111 families with non-syndromic mild to profound hearing impairment. An additional family with Vohwinkel syndrome, a combination of hearing impairment and palmoplantar keratoderma with constriction of the digits, was also included. We used direct sequencing analysis to detect all possible coding GJB2 variants in this population. The presence of the g.1777179_2085947del mutation (hereafter called del(GJB6-D13S1830)) was also investigated as it was shown to be the second most common mutation causing non-syndromic prelingual hearing impairment in Spain. Sequencing analysis of one randomly chosen individual per family revealed that the c.35delG mutation was present in 24 out of 222 chromosomes (10.8%), making it the most frequent mutation in the GJB2 gene in Egypt. Five other mutations were already described previously [p.Thr8Met, p.Val37Ile, p.Val153Ile, c.333_334delAA, c.1-3172G>A (commonly designated as IVS1+1G>A)]. This study also revealed three other novel gene variants resulting in amino acid substitutions (p.Phe142del, p.Asp117His, p.Ala148Pro). In contrast with most populations, the del(GJB6-D13S1830) mutation upstream of the GJB2 gene was not present in this Egyptian population. A dominant mutation at a highly conserved residue, p.Gly130Val, was found in the family with Vohwinkel syndrome.

Adult↗
PubMed1987

On the role of repeated sequences 5' to variant surface glycoprotein genes in African trypanosomes.

In African trypanosomes, the DNA region situated upstream from all active and some silent variant surface glycoprotein genes (VSG genes) has a repetitive structure. This region is composed of a variable number of tandem repeats of an A + T-rich sequence which lacks the recognition sites for most commonly used restriction endonucleases, and is thus called 'barren region'. The length of the barren regions varies in different trypanosome variants from 0.2 to many kb. We have characterized the barren region upstream from the active VSG gene in two independent Trypanosoma equiperdum variants expressing the same VSG gene in the same expression site. To analyse the junction point between the expression site and the inserted gene, these two barren regions were cloned and sequenced. The longer barren region contains 14 repeats and the other contains two repeats. In both cases the junction point has been shown to lie within a repeat but different repeats were used in each case. These results argue that the repeats are important for the insertion of the duplicated-transposed gene into the expression site and that any repeat can be used.

Animals↗
PubMed1991

Characterization of HBV2-like infections in Spain.

Hepatitis B viral serum markers suggestive of infection by hepatitis B virus type 2 were found in 354 patients tested in the laboratory during a 2.5 year period of study. Confirmation of the HBsAg reactivity by neutralization and subtyping analysis and determination of serum HBV-DNA by molecular hybridization were carried out on selected samples from these patients. Clinical and epidemiological data were obtained from 234 patients and serological follow-up was done in 70 cases. The results obtained from the confirmatory tests and DNA assays indicated that HBsAg reactivities were specific, being frequently associated to low levels of HBV-DNA. The incidence rates obtained for HBV2 serological patterns among patients at different level of risk for HBV infection, as well as the finding of a high rate of coinfection with hepatitis A virus among those showing acute hepatitis, suggested that the HBV2 agent could be transmitted by the oral route. An hypothesis considering the so called HBV2 infections as resulting from infections by an HBV variant strain which has an improved ability for non-sexual, non-parenteral transmission is suggested. Specific recommendations for detection and confirmation of such cases in blood banks are also outlined.

Adolescent↗
PubMed1997

Multiple conformational states of the bacteriophage T4 capsid surface lattice induced when expansion occurs without prior cleavage.

The maturation pathway of bacteriophage T4 capsid provides a model system for the study of largescale conformational changes, in that the precursor capsid progresses through four long-lived and widely differing states. The surface lattice first assembled (uncleaved/unexpanded state: hexagonal lattice constant, a = 11.8 nm) undergoes proteolytic cleavage (cleaved/unexpanded state), then expands (cleaved/ expanded state: a = 14.0 nm), and then binds accessory proteins. The most profound change, expansion, normally follows cleavage of the major capsid protein gp23 to gp23* (the 65-residue N-terminal "delta-domain" is removed), but can be induced in vitro in the absence of cleavage by treatment with 0.25 M guanidine-HCl (uncleaved/expanded state). We have studied this alternative pathway by negative staining electron microscopy of polyheads (tubular capsid variants). We find that uncleaved/expanded polyheads encompass four discrete states, called G1-G4, distinguished by their lattice constants of 12.6 nm (G1), 13.4 nm (G2), and 14.0 nm (G3, G4) and by the structures of their hexameric capsomers. Viewed in projection, the G4 capsomer differs from the cleaved/ expanded capsomer only in the presence of additional mass at one site per protomer. This mass correlates with the presence of the delta-domain, which translocates from the inner to the outer surface when the uncleaved lattice expands. Based on proximity of resemblance among these capsomers, we suggest that G1 to G4 represent a sequence of transitional states whose endpoint is G4. G1, G2, and G3 may correspond to intermediates that are too short-lived to be observed when the cleaved lattice expands, but are trapped by the retention of delta-domains at the interfaces between subunits in the uncleaved lattice.

Bacteriophage T4↗
PubMed2007

Conditional mutagenesis by cell-permeable proteins: potential, limitations and prospects.

The combination of two powerful technologies, the Cre/loxP recombination system and the protein transduction technique, holds great promise for the advancement of biomedical and genome research by enabling precise and rapid control over mutation events. Protein transduction is a recently developed technology to deliver biologically active proteins directly into mammalian cells. It involves the generation of fusion proteins consisting of the cargo molecule to be delivered and a so-called protein transduction domain. Recently, the derivation of cell permeable variants of the DNA recombinase Cre has been reported. Cre is a site-specific recombinase that recognizes 34 base pair loxP sites and has been widely used to genetically engineer mammalian cells in vitro and in vivo. Recombinant cell-permeable Cre recombinase was found to efficiently induce recombination of loxP-modified alleles in various mammalian cell lines. Here we review recent advances in conditional expression and mutagenesis employing cell-permeable Cre proteins. Moreover, this review summarizes recent findings of studies aimed at deciphering the molecular mechanism of the cellular uptake of cell-permeable fusion proteins.

Amino Acid Sequence↗
PubMed1981

Tumor-like amyloid formation (amyloidoma) in the brain.

An almost walnut-sized tumor was removed surgically from the left occipital lobe of a 46-year-old woman, who had suffered for 4 year from progressive visual loss with scotoma and finally from hemianopia, associated with attacks of headaches and recurrent episodes of depression each lasting for some weeks or months. Neuropathological examination, including polarization, thioflavine, fluorescence, immunofluorescence staining, and electron microscopy, revealed an amyloidoma, which consisted of broad appositionally grown amyloid deposits surrounded by some plasma cells, monocytic or foreign body cell types. The massive accumulations, often associated not only with blood vessels or perivascular collagenous fibers but also lying in the cerebral tissue not unlike senile plaques in the cortical gray matter corresponded to gradually growing masses as seen in the repeated CT scans. This unique lesion in the brain of a patient who did not show any evidence of systemic disorder, seems to confirm that the spontaneous tumor-like amyloid, which gave an immunofluorescent staining mainly with anti-IgM, is a special variant of primary amyloidosis (amyloid L) or of so-called paramyloid.

Amyloid↗
PubMed2004

Infantile Refsum disease: serial evaluation with MRI.

Refsum disease is a rare metabolic disorder, which is characterized by the accumulation of phytanic acid in the blood and tissues, including the brain. A variant of this condition that occurs in young children is called infantile Refsum disease. The MRI findings of symmetrical signal change involving the corticospinal tracts, cerebellar dentate nuclei, and corpus callosum are characteristic. We report the serial MRI findings of a child with this rare metabolic disorder.

Brain↗