Genetic Peculiarities Research Articles

Are cheetahs on the run from prion-like amyloidosis?

The misfolding and aggregation of proteins is often an accident waiting to happen. Consequently, organisms have developed sophisticated chaperone and quality-control systems to limit abnormal protein interactions and the accumulation of toxic aggregates (1). However, sometimes these systems can be overwhelmed, and diseases, namely protein misfolding diseases, can result. One such disease, amyloid protein A (AA) amyloidosis, is wreaking havoc in the captive cheetah population, complicating efforts to rescue this endangered species from extinction (2, 3). One key to managing this fatal disease in cheetahs is to understand why it is so prevalent. Most cases of AA amyloidosis in mammals appear to occur spontaneously, usually as a result of chronic inflammation or genetic peculiarities that predispose the organism to the deposition of serum amyloid A (SAA) protein in fibrillar deposits called amyloid (Fig. 1). In this issue of PNAS, Zhang et al. (4) report that AA amyloid is excreted in the feces of cheetahs with AA amyloidosis and that this fecal amyloid can in turn promote a similar disease in mice. These results suggest that cheetah AA amyloidosis may not be simply a spontaneous disease, but also a natural prion-like, transmissible protein misfolding disease.

Phylogenetic analysis of hemagglutinin, neuraminidase, and nucleoprotein genes of H9N2 avian influenza viruses isolated in Israel during the 2000–2005 epizootic

The first two isolates of H9N2 influenza virus in Israel were collected from turkey and chicken hosts in May 2000. The actual epizootic of the H9N2 virus started in December 2001, after a 1.5-year period of silence, and still continues. A total of more than 500 isolations from turkeys and chickens were registered during the outbreaks. The present study has revealed some genetic peculiarities among the local isolates, namely: all the isolates belong to the same G1-like phylogenetic lineage, within which they form a single group, which, in turn, is divided into three subgroups in the cases of the HA and NP genes, and two subgroups in the case of the NA gene. The results present a basis for suggesting the existence of two parallel evolutionary trends originating from the same local "prototype" isolate.

Polymorphism of detoxification genes and cell resistance to mutagens in patients with Ehlers-Danlos syndrome

Study of polymorphism in 3 genes of the glutathione S-transferase family (GSTM1, GSTT1, and GSTP1) in children with Ehlers-Danlos syndrome whose cells were defective in repair of gamma-induced DNA damages revealed accumulation of GSTM1(+) genotypes compared to children of the control group. Generation of reactive oxygen species by neutrophils from patients with this syndrome was higher than in healthy donors. Our results indicate that glutathione S-transferase genes are involved in the resistance to mutagenic agents and demonstrate medical and genetic peculiarities of patients with Ehlers-Danlos syndrome.

Microevolution and Patterns of Dissemination of the JP2 Clone of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans

The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82 A. actinomycetemcomitans strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes hbpA and tbpA. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.

Mitochondrial DNA diversity of the Amerindian populations living in the Andean Piedmont of Bolivia: Chimane, Moseten, Aymara and Quechua

Background: Chimane, Moseten Aymara and Quechua are Amerindian populations living in the Bolivian Piedmont, a characteristic ecoregion between the eastern slope of the Andean mountains and the Amazonian Llanos de Moxos. In both neighbouring areas, dense and complex societies have developed over the centuries. The Piedmont area is especially interesting from a human peopling perspective since there is no clear evidence regarding the genetic influence and peculiarities of these populations. This land has been used extensively as a territory of economic and cultural exchange between the Andes and Amazonia, however Chimane and Moseten populations have been sufficiently isolated from their neighbour groups to be recognized as distinct populations. Genetic information suggests that evolutionary processes, such as genetic drift, natural selection and genetic admixture have formed the history of the Piedmont populations.Aim: The objective of this study is to characterize the genetic diversity of the Piedmont populations, analysing the sequence variability of the HVR-I control region in the mitochondrial DNA (mtDNA). Haplogroup mtDNA data available from the whole of Central and South America were utilized to determine the relationship of the Piedmont populations with other Amerindian populations.Subject and methods: Hair pulls were obtained in situ, and DNA from non-related individuals was extracted using a standard Chelex™ 100 method. A 401 bp DNA fragment of HVR-I region was amplified using standard procedures. Two independent 401 and 328 bp DNA fragments were sequenced separately for each sample. The sequence analyses included mismatch distribution and mean pairwise differences, median network analyses, AMOVA and principal component analyses. The genetic diversity of DNA sequences was measured and compared with other South Amerindian populations.Results: The genetic diversity of 401 nucleotide mtDNA sequences, in the hypervariable Control Region, from positions 16 000–16 400, was characterized in a sample of 46 Amerindians living in the Piedmont area in the Beni Department of Bolivia. The results obtained indicate that the genetic diversity in the area is higher than that observed in other American groups living in much larger areas and despite the reduced size of the studied area the human groups analysed show high levels of inter-group variability. In addition, results show that Amerindian populations living in the Piedmont are genetically more related to those in the Andean than in the Amazonian populations.

Altered Natural Killer Cells in Type 1 Diabetic Patients

Evidence from animal models suggests that natural killer (NK) cells can be important players in the development of type 1 diabetes, although data in humans are still sparse. We studied the frequency and activation state of blood NK cells at different stages of human type 1 diabetes, and whether genetic or phenotypic NK cell peculiarities could be associated with an early onset of diabetes. The onset period is marked by a slight reduction in blood NK cells, but these are unusually activated in some patients (gamma-interferon expression). This activation status does not correlate, however, with a particularly young age at onset. In contrast, NK cells in patients with long-standing type 1 diabetes had a markedly lower expression of p30/p46 NK-activating receptor molecules compared with those of control subjects. A slightly decreased expression of NKG2D in all type 1 diabetic patients relative to control subjects was observed, independent of the duration of disease, parallel to prior observations in the NOD mouse. Finally, type 1 diabetic patients had an increased frequency of KIR gene haplotypes that include the activating KIR2DS3 gene, with a genetic interaction between the KIR and HLA complexes. The reduced activation of NK cells in individuals with long-standing type 1 diabetes would seem to be a consequence rather than a cause, but other peculiarities may relate to type 1 diabetes pathogenesis.

Glory phenomenon informs of presence and phase state of liquid water in cold clouds

Although the optical phenomenon of glory on cloud tops with negative temperatures is now widely known to be observable from aircraft, the information thereby obtained on cloud microphysics remains not called for. The analysis made in the present work is based on a comparison between the features of the glory phenomenon, geometric theory of bow formation, and Mie scattering theory. The convincing evidence has been provided that this sort of glory forms as a first-order bow from spherical particles with a refractive index of 1.81–1.82 and diameter over 20 μm. Thus obtained are solutions of two interrelated problems: (i) the cold-cloud glory is proved to be a bow formed from spheres with those unusual optical properties, (ii) once more corroboration is gained of earlier discovered existence in cold clouds of droplets of liquid water in specific phase state referred to amorphous water, or A-water. Physico-chemical and genetic peculiarities of A-water are briefly summarized here. The results obtained show that a detailed study and monitoring of the glory phenomenon are of great interest since the occurrences of the phenomenon itself as well as its geometrical and photo-chromatic characteristics provide unique remote information about the disperse phases of cold clouds. The visible size of the glory can serve as an indicator of the maximum size of A-water droplets, and its extra outer rings must reveal the presence of some forms of ice crystals.

Microsatellite polymorphism in Italian populations of northern pike ( Esox lucius L.)

Northern pike ( Esox lucius) is not considered an endangered species in Italy, but since recent studies indicate the decline of this population, conservation and management strategies based on the genetic differentiation of natural northern pike populations are needed. In this paper, genetic diversity was analysed in 10 Italian and 2 East European northern pike populations by means of seven microsatellite loci. Data indicated an appreciable genetic differentiation, in spite of a low genetic variation, and agreed with the low level of genetic polymorphism already observed for this species in North America and North Europe. Results of statistical tests revealed genetic peculiarities of the Italian populations, even though signals of recent contact between populations were found and discussed in relation to anthropic impacts, particularly to the stocking practice. This investigation represents the first approach to the knowledge of the genetic variability of Italian pike populations using microsatellite markers, and reported results could be of interest for future management and conservation programmes of this species in Italy.

Comparative morphological, ecological, and molecular studies of Aspergillus versicolor (Vuill.) tiraboschi strains isolated from different ecotopes

Cultural, morphological, ecological, and trophic properties (growth at different temperatures and on various organic substrates), as well as molecular and genetic peculiarities of Aspergillus versicolor (Vuill) Tiraboschi strains of different origins, were determined. The strains were isolated from different ecotopes (upper horizons of modern soils of several geographic regions, ancient soils and peat, and permafrost). No essential distinctions in cultural and morphological properties were revealed between the strains. Strains obtained from peat of the Aleutian Islands were characterized by the highest radial rates of colony growth. Some variations in the ITS loci of rDNA were observed in strains isolated from different ecotopes; the distinctions were most pronounced (1.7%) in the strain isolated from 100 000-year-old permafrost.

Genetic study of Sardinian patients with Alzheimer's disease

We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the γ-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G > C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the ɛ4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.

Vitamin E deficiency ataxia with (744 del A) mutation on α-TTP gene: genetic and clinical peculiarities in Moroccan patients

Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich’s ataxia (FA). Molecular analysis is needed for an early differential diagnosis, in order to initiate therapeutic vitamin E supplementation before damage develops. We studied 16 patients from seven Moroccan families presenting an autosomal recessive Friedreich-like ataxia with vitamin E deficiency. Our patients were homozygous for 744 del A mutation of α-TTP gene. Compilation of clinical records revealed a great phenotypic variability and some features indicating a new possible role of vitamin E in hypothalamo-hypophysial system regulation and cardiomyopathy prevention. Early vitamin E supplementation may provide considerable improvement of neurological signs and other associated abnormalities. Clinical heterogeneity is for involvement of other non-genetic defect and indicated another role of vitamin E, which should be better studied.

Vitamin E deficiency ataxia with (744 del A) mutation on ?-TTP gene: genetic and clinical peculiarities in Moroccan patients

Vitamin E deficiency ataxia with (744 del A) mutation on ?-TTP gene: genetic and clinical peculiarities in Moroccan patients

Hematological malignancies in the island of Sardinia, 1974–1993: age and sex distributions and temporal changes in incidence

We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974-1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984-1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia.

?-globin gene cluster haplotypes associated with ?-thalassemia on Corsica island

In the Corsican population, the incidence of beta-thalassemia traits is reported to be 3.1%. We have investigated the 2 more important beta-thalassemia mutations present in the Corsican population: beta0-39 and beta+IVS1-110. Seven polymorphic sites in the beta-globin gene cluster were analyzed from a sample of 43 non-related beta-thalassemia heterozygotes and of 47 nonrelated healthy individuals, from Central Corsica (Corte). Among the 43 Corsican patients analyzed, the nonsense codon is predominant (88.40%), whereas the beta+IVS1-110 mutation, the most common of beta-thalassemia in the eastern part of the Mediterranean basin, is underrepresented (2.33%). The other individuals did not show positive for the two tested mutations (9.27%). The beta0-39 mutation in the studied population shows a strong association with haplotype II (18.7%) and a weaker association with haplotypes I (2.3%) and VII (2.1%). The strong association of the beta0-39 mutation with haplotype II was also found in Sardinia, suggesting that the mutation on the two islands have the same origin. In the present study all the data concerning frequencies of the mutations and of sequence haplotypes, support the hypothesis of a western Mediterranean origin of the beta0-39 mutation. For the first time, this paper analyzes the association of beta-globin gene cluster haplotypes with the 2 more frequent beta-thalassemia mutations in an isolated population in the centre of Corsica (Corte), which presents certain genetic peculiarities. However, the analysis of beta-haplotypes will be very useful for the genetic epidemiological study in this region.

Molecular–genetic peculiarities of classical biotype Vibrio cholerae, the etiological agent of the last outbreak Asiatic cholera in Russia

Molecular–genetic properties of classical biotype Vibrio cholerae strains that caused the Asiatic cholera outbreak in 1942 in Russia have been investigated for the first time. Being characterized by high-level production of cholera toxin and toxin-coregulated adhesion pili both of which are the major virulence factors, all the strains studied, in contrast to the typical cholera pathogens, were autographic requiring purine and/or amino acids added to the minimal medium for their growth. Moreover, these strains containing the structural gene hapA, as shown by the polymerase chain reaction, produced no soluble hemagglutinin/protease, which enables the vibrios to get disseminated in the environment. The peculiarities of the natural V. cholerae strains elucidated in the work are likely to be responsible for the unusual infectious and epidemic processes observed during that cholera outbreak.

Acetate metabolism and its regulation in Corynebacterium glutamicum

The amino acid producing Corynebacterium glutamicum grows aerobically on a variety of carbohydrates and organic acids as single or combined sources of carbon and energy. Among the substrates metabolized are glucose and acetate which both can also serve as substrates for amino acid production. Based on biochemical, genetic and regulatory studies and on quantitative determination of metabolic fluxes during utilization of acetate and/or glucose, this review summarizes the present knowledge on the different steps of the fundamental pathways of acetate utilization in C. glutamicum, namely, on acetate transport, acetate activation, tricarboxylic acid (TCA) cycle, glyoxylate cycle and gluconeogenesis. It becomes evident that, although the pathways of acetate utilization follow the same theme in many bacteria, important biochemical, genetic and regulatory peculiarities exist in C. glutamicum. Recent genome wide and comparative expression analyses in C. glutamicum cells grown on glucose and on acetate substantiated previously identified transcriptional regulation of acetate activating enzymes and of glyoxylate cycle enzymes. Additionally, a variety of genes obviously also under transcriptional control in response to the presence or absence of acetate in the growth medium were uncovered. These genes, thus also belonging to the acetate stimulon of C. glutamicum, include genes coding for TCA cycle enzymes (e.g. aconitase and succinate dehydrogenase), for gluconeogenesis (phosphoenolpyruvate carboxykinase), for glycolysis (pyruvate dehydrogenase E1) and genes coding for proteins with hitherto unknown function. Although the basic mechanism of transcriptional regulation of the enzymes involved in acetate metabolism is not yet understood, some recent findings led to a better understanding of the adaptation of C. glutamicum to acetate at the molecular level.

Polyploidy and polyteny in the gigantic eubacterium Epulopiscium fishelsoni

Content and distribution of basic proteins, histones, acidic proteins and DNA, as well as the interaction of basic proteins with DNA, were studied microfluorometrically within nucleoid bodies of the gigantic eubacterium Epulopiscium fishelsoni living in the guts of the algivorous surgeonfish Acanthurus nigrofuscus. The fine structure of the bacterial nucleoid was studied using transmission electron microscopy (TEM). The mean content of basic proteins, histones and acidic proteins per nucleoid was directly proportional both to cell volume and DNA amount, proving that these proteins are integral components of bacterial chromatin. The maximal DNA quantity of ~1012 base pairs nucleoid−1 was found in the largest specimens of 354,000 µm3 volume (150-fold more then in human lymphocyte). Binding of proteins to DNA was strongest in cup-like nucleoids at the end of the bacterial life cycle, and weakest in enlarged and elongated nucleoids in mid-cycle. Contact fluorescent microscopy and TEM revealed a non-homogenous distribution of these proteins within the nucleoids, as well as the presence of giant polytene chromosome(s). We assume that the unusual genetic and morphological peculiarities, particularly increased polyploidy and polyteny, as revealed in E. fishelsoni, are the results of specific adaptations to the chemical conditions in the host's gut.

Hybrids of human and monkey adenoviruses (adeno-adeno hybrids) that can reproduce in monkey cells: biological and molecular genetic peculiarities

A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.

Cancerous genetic peculiarities non-responsible for cancer development

Certain genetic peculiarities recently identified in cancer cells have generally been regarded as the abnormalities responsible for cancer development. However, these abnormalities may also be found in maturable cancer cells and are not limited only to the non-maturable type. As previously described by the authors (1–3,5,6), cancer tissue consists of two types of cancerous cells: maturable and non-maturable. The development of cancer may be dependent only on the non-maturable cancerous stem cells, not on the maturable type. Since the non-maturable cell may be solely responsible for carcinogenesis, the relevant genetic peculiarities that are also found in the maturable cancer cells should not be regarded as the abnormalities responsible for carcinogenesis.

HLA complex antigens at infantile cerebral paralysis in Kazan population

A complex clinico-instrumental and immunogenetic study has been performed in 34 patients with different forms of infantile cerebral palsy in Kazan population. HLA-typing has revealed a reliable disease association with antigen B13. The control group was made up of 115 healthy patients. For the first time a comparable risk criteria has been counted: if a patient has B13 antigen risk of infantile cerebral paralysis development increases by 3.55 times. Contribution of HLA-B13 associated gene into genesis of the disease makes up not less than 11,6%. The study results testify to heridatary mechanisms envolvement into etiopathogenesis of infantile cerebral paralysis and demand further study of genetic peculiarities of susceptibility genome to different harmful factors.