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PubMed1989

Ordovician paleosols at Arisaig, Nova Scotia, and the evolution of the atmosphere.

A series of Late Ordovician andesite flows are exposed along the coastline near Arisaig, Nova Scotia. Field relationships, textural and mineralogical evidence, and chemical analyses of three interflow units confirm that they are paleosols. The chemical variations observed in these paleosols are quite similar to those of modern soils developed on mafic volcanic rocks. Virtually all of the iron in the paleosols was oxidized and retained during weathering; however, in two of the three paleosols a small fraction of the ferrous iron escaped oxidation and was precipitated near the base of the paleosols. This redistribution of ferrous iron may reflect the presence of nonvascular land plants. The variations in the concentration of the major oxides produced by weathering of the andesites at Arisaig are consistent with the probable lower limit of 0.04 atm for the partial pressure of O2 in the atmosphere during the Late Ordovician. The current data base for Paleozoic and Precambrian paleosols indicates that a significant increase in the PO2/PCO2 ratio in the atmosphere took place about 2.0 x 10(9) years ago; since then the ratio of PO2/PCO2 in the atmosphere has been high enough to oxidize all of the iron in soils developed on igneous rocks.

Atmosphere↗

PubMed1992

[Exercise echocardiography in coronary disease].

Exercise echocardiography is a new method used in the investigation of coronary disease. It evaluates the repercussions on regional contractile function of the increase in oxygen consumption induced by physical exercise. It makes it possible to analyse in real time not only the amplitude of endocardial displacement, but also that of parietal thickening and thereby seems to be more precise than conventional ergonomic tests in the diagnosis of myocardial ischaemia. Its recent development owes much to the advent of digital technologies which make it easier and more accurate to interpret the changes observed in left ventricular regional kinetics by comparing the data at rest with those recorded at peak physical effort. When associated with an equally non-invasive ergometric test it is well accepted by the patients. Another of its advantages is its moderate cost. Echocardiographists must devote as much time as necessary to training. Training is indispensable to rapidly capture the images, particularly during efforts, and to reliably interpret the variations observed in left ventricular wall contraction. Exercise echocardiography is still under evaluation. Experience is lacking for the cardiologist to choose, only on its results, the most appropriate treatment for each individual patient, but its help will be appreciated in some difficult therapeutic decisions. Behind this phase of training for, and evaluating this technique several of its main clinical indications can already be outlined.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

PubMed1994

Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility.

BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of morphologic examination in transitional cell carcinomas of the urinary bladder (TCC) may be subject to observer variation, resulting in a reduced level of reproducibility. This may confound comparisons of treatment results. Using objective, unbiased stereologic techniques and ordinary histomorphometry, such problems may be solved. EXPERIMENTAL DESIGN: A study of 110 patients with papillary or solid transitional cell carcinomas of the urinary bladder in stage Ta through T4 was carried out, addressing reproducibility of both qualitative and quantitative grading methods. Grading of malignancy was performed by one observer in Japan (using the World Health Organization scheme), and by two observers in Denmark (using the Bergkvist system). A "translation" between the systems, grade for grade, and kappa statistics were used in evaluating the reproducibility. Unbiased estimates of nuclear mean volume, nuclear mean profile area, nuclear volume fraction, nuclear profile density index, and mitotic profile density index were obtained twice in 55 of the studied cases by one observer in Japan and one in Denmark, using a random, systematic sampling scheme. RESULTS: The results were compared by bivariate correlation analyses and Kendall's tau. The international interobserver reproducibility of qualitative gradings was rather poor (kappa = 0.51), especially for grade 2 tumors (kappa = 0.28). Likewise, the interobserver agreement on the Bergkvist scheme was poor (kappa = 0.43). On the other hand was the interobserver agreement on invasion high (kappa = 0.75). The intraobserver reproducibility of the quantitative histopathologic variables was excellent in both Japan and Denmark for estimates of nuclear mean volume (r = 0.93), for nuclear mean profile area (0.78 < r < 0.83), and for nuclear profile density index (0.85 < r < 0.89), whereas the reproducibility for nuclear volume fraction was somewhat poorer (0.68 < r < 0.64). The slopes of the correlation lines were not significantly different from unity. Estimates of mitotic profile density index also showed acceptable intraobserver reproducibility (Kendall's tau > 0.53). CONCLUSIONS: The international, interobserver reproducibility of the quantitative estimators yielded similar results for all histopathologic variables investigated, except for nuclear volume fraction (r = 0.54). This can probably be related to the manual design of the sampling scheme and may be solved by introducing a motorized object stage in the systematic selection of fields of vision for quantitative measurements. However, the nuclear mean size estimators are unaffected by such sampling variability. The results obtained in this study stress the need for objective, quantitative histopathologic techniques substituting qualitative, subjective methods in prognosis-related grading of malignancy.

Adult↗

PubMed2000

Individual variation in somatic mutations of the glycophorin-A gene in neonates in relation to pre-natal factors.

The frequency of somatic mutations of the glycophorin-A (GPA) gene was measured in red blood cells from a series of newborn babies and related to various epidemiological and lifestyle factors in order to identify those factors that might influence the mutation rate before birth. Although there was substantial variation in the mutation frequencies between individual babies, no specific associations were found with any of the factors explored including smoking, age and social class of the parents, and gender and birth weight of the babies. It is concluded that these factors do not have a substantial effect on the mutational endpoint measured, although this does not necessarily mean that they have no effect on health risk to the offspring. The observed variation in GPA gene mutation frequency must, therefore, be due either to exposure to less obvious external influences or to intrinsic factors.

Adolescent↗

PubMed1982

Early course of infection in susceptible and resistant strains of mice, using [3H]uridine-labeled Trypanosoma brucei subsp. brucei.

A radioisotopic technique utilizing [3H]uridine was developed to determine the tissue distribution of intravenously inoculated Trypanosoma brucei spp. brucei in susceptible (Swiss-Webster) and resistant (deer) strains of mice. The reliability of the technique was tested by using unincorporated [3H]uridine and heat-killed (labeled) trypanosomes in parallel experiments. The inoculations with viable (labeled) organisms showed that during the initial 24 h T. brucei subsp. brucei was cleared from the bloodstream of deer mice to a significantly greater extent than in Swiss-Webster mice. In addition, significantly more radioactivity was found in the liver, spleen, and kidneys of the deer mice. Autoradiographs of trypanosomes in selected tissues supported the distribution observed with labeled organisms. All of the above experiments involved the highly virulent, monomorphic bloodstream form of T. brucei subsp. brucei. Similar experiments with less virulent tissue culture-adapted trypanosomes showed that these organisms were readily cleared from the bloodstream, even in highly susceptible Swiss-Webster mice. The results suggest that avoidance of phagocytosis may be an important virulence factor of T. brucei subsp. brucei and contributes to the variation observed in species and strain susceptible to trypanosomiasis.

Animals↗

PubMed2006

Crossover frequency and synaptonemal complex length: their variability and effects on human male meiosis.

In this study, immunocytogenetics has been used in combination with the subtelomere-specific multiplex-fluorescent in-situ hybridization (stM-FISH) assay to identify 4681 autosomal synaptonemal complexes (SCs) of two fertile men. Comparisons of crossover maps for each individual SC between two men with extremely different meiotic crossover frequencies show that a low crossover frequency results in (i) a higher frequency of XY pairs and of small SCs without MLH1 foci and (ii) lower frequency of crossovers in the proximity of centromeres. In both cases, the bivalents which most frequently lacked MLH1 foci were the XY pair and the SC21. Analysis of SC length showed that SC arms can be longer or shorter than the corresponding mitotic one. Moreover, for a given SC, the variation in length found in one arm was independent of the variation observed in the other one (e.g. SC1p arms are longer than SC1q arms). The results confirmed that reduction in the crossover frequency may increase the risk of achiasmate small bivalents and that interindividual differences in crossover frequency could explain the variability in the frequencies of aneuploidy in human sperm. How MLH1 foci are positioned within the SC is discussed based on detailed MLH1 foci distributions and interfoci distances. Finally, evidence that the variation of the SC arm length may reflect the abundance of open and of compact chromatin fibers in the arm is shown.

Chromosome Mapping↗

PubMed1993

Active core rewarming in neurologic, hypothermic patients: effects on oxygen-related variables.

OBJECTIVES: To determine in hypothermic patients if a) the decrease in oxygen consumption (VO2) is exclusively dependent on the decrease in metabolic rate, or b) as a consequence of the greater hemoglobin affinity for oxygen, hypothermic tissues have impaired oxygen extraction. DESIGN: Clinical, prospective study; sequential measurements of oxygen-related variables during active core rewarming. SETTING: Intensive care unit of a university hospital. PATIENTS: Twelve patients (44 +/- 16 yrs of age) admitted to the intensive care unit with a core temperature of < 34 degrees C due to severe neurologic damage. INTERVENTIONS: Rewarming (with heated enemas, gastric infusions, and heated blankets) to increase body temperature at a rate of approximately 1 degree C/hr. Measurements of oxygen-related variables were performed at a baseline of 31.0 +/- 1.1 degrees C, and repeated at each 1 degree C increase to reach a core temperature of approximately 35 degrees C. MEASUREMENTS AND MAIN RESULTS: Oxygen-related variables of rewarmed patients were allocated into two groups, above or below the observed mean core temperature of 33.1 degrees C recorded for all measurements (n = 45). Comparison of the low core temperature group (31.1 +/- 1.4 degrees C; n = 20) with the high core temperature group (34.7 +/- 0.9 degrees C; n = 25) showed that the group with the lower core temperatures had a significant increase in VO2 index (67 +/- 22 vs. 103 +/- 38 mL/min/m2 [p < .001]), oxygen delivery index (183 +/- 73 vs. 290 +/- 123 mL/min/m2 [p < .001]), and the PO2 value at which hemoglobin was half-saturated with oxygen ([P50] 23 +/- 5.7 vs. 27.7 +/- 5.7 torr [3.0 +/- 0.7 vs. 3.6 +/- 0.7 kPa] [p < .02]). An increase in metabolic acidosis could be observed in the lower temperature group: arterial pH 7.47 +/- 0.15 vs. 7.34 +/- 0.13 (p < .01); base deficit -3.7 +/- 6.7 vs. -8.2 +/- 4.9 mEq/L (p < .02). The oxygen extraction ratio remained unchanged: 0.39 +/- 0.10 vs. 0.38 +/- 0.10 (NS). CONCLUSIONS: These data show that VO2 was reduced to half of normal values during hypothermia. Active core rewarming produced an average 4.5% increase in VO2 per 1 degree C that was characterized by the wide variation observed in this metabolic response between different patients and for individual cases. Despite the rightward shift of P50 observed during rewarming (mainly due to the Bohr effect), no change was reflected on the oxygen extraction ratio.

Acidosis, Lactic↗

PubMed1998

Morphological, physiological and metabolic comparisons between runner-like and sheet-like inbred lines of a colonial hydroid.

Hydractiniid hydroids display a range of morphological variation from sheet-like forms (i.e. closely spaced polyps with high rates of stolon branching) to runner-like forms (i.e. widely spaced polyps with low rates of stolon branching), thus exemplifying the patterns of heterochrony found in many colonial animals. A sheet-like and a runner-like inbred line of Podocoryne carnea were produced to investigate this heterochronic variation further. Selection on colony morphology at the time of the initiation of medusa production resulted in dramatic differences by the F5 and F6 generations. Compared with colonies of the sheet-like inbred line, runner-like colonies exhibited smaller sizes at the initiation of medusa production, more irregular colony shapes and diminished stolon development relative to polyp development. In addition to these differences in colony morphology, runner-like colonies also exhibited larger medusae and a greater amount of gastrovascular flow to the peripheral stolons. To assess differences in the metabolic capacity underlying this variaton in flow, the redox state of the polyp epitheliomuscular cells was measured using the fluorescence of NAD(P)H. In response to feeding-induced changes in gastrovascular flow, runner-like colonies show greater redox variation than sheet-like ones, plausibly corresponding to the greater amounts of flow generated by the former colonies relative to the latter. Perturbing the system with dilute solutions of 2,4-dinitrophenol similarly indicates that runner-like colonies contain more functionally oxidizable NAD(P)H. The correlation between gastrovascular flow and morphological differences supports the hypothesis that the former mediates the timing of colony development, perhaps in concert with the observed variation in the redox state of polyp epitheliomuscular cells.

Journal Article↗

PubMed1995

Plasmodium falciparum: variations within the C-terminal region of merozoite surface antigen-1.

Sequence variations at the 3'-end of the Plasmodium falciparum merozoite surface antigen-1 gene show that the C-terminus of the protein may not be as conserved as has been assumed in the past. We have therefore examined the sequences of the 3' terminal 2 kb, i.e., blocks 12-17 of four isolates, RO-33, RO-71, 3D7A, and FCH5. We discuss different mechanisms of genetic exchange that could account for the observed variations. Furthermore the deduced amino acid sequences allow us to identify allelic epitopes of three monoclonal antibodies. Finally, our data complete the sequence of two additional independent alleles of this gene (RO-33 and RO-71).

Animals↗

PubMed2001

Distribution, abundance, and habitat preferences of Ixodes ricinus (Acari: Ixodidae) in northern Spain.

Ixodes ricinus (L.) was collected by standard dragging in 2,082 different sites in 18 broad vegetation categories in northern Spain to explore the influence of vegetation on its abundance. Of these, 785 sites were surveyed in 1995, 636 in 1996, and 661 in 1997. The impact of habitat features on differences in tick numbers is addressed. The tick was present in low numbers in areas of old, heterogeneous coniferous forests. Ticks appeared to prefer sites that had substantial secondary plant growth such as river canopies, heterogeneous Pinus uncinata forests, mixed forests, and deciduous heterogeneous woods. Highest tick abundance was recorded for sites that contained Quercus spp., as well as for mixed old forests that had many ecotones. I. ricinus was absent in open habitats, homogeneous young coniferous forests, and open hillsides. These differences were attributed to greater shrub cover and litter depth, which created more favorable microclimatic conditions for tick survival. The abundance of I. ricinus nymphs was not homogeneous in sites within the same habitat category and vegetation physiognomy at these sites did not appear to cause differences in tick abundance. Analysis of variance (ANOVA) indicated that variation in tick abundance could be explained by the exposure of the sampled site, at least for some zones within deciduous forest categories. However, this factor did not explain the variation observed in other habitats. Temperature and vegetation (normalized derived vegetation index) features were recorded daily by remotely sensed imagery throughout the study period and the data were used to obtain long-term mean and maximum values of the physical parameters considered. Multiple regression analysis performed between these long-term abiotic factors and nymphal abundance in positive sites showed high relationship (R2 coefficients) for every habitat category and explained >50% of the variation in tick abundance.

Animals↗

PubMed1985

Circadian rhythm of the pupillary response to morphine and to naloxone.

Mice respond to morphine with characteristic mydriasis which is antagonized by naloxone. The present study presents data on the diurnal variation of these responses. The mydriatic response is at its highest level at 0800 and has a nadir at 2400. This effect is not influenced by ambient light conditions. The miotic response to naloxone in the morphine-dilated pupil is maximal between 1200 and 1600 and minimal at 0400. The curves of the responses to the two drugs, therefore, differ as do their acrophases. Pharmacokinetic factors are probably not responsible for the observed variations. It is speculated that these diurnal changes may reflect cyclic alteration in the affinity of the opiate receptors to agonists and antagonists, respectively, or in the number of available receptors.

Animals↗

PubMed2005

Body size, energy metabolism and lifespan.

Bigger animals live longer. The scaling exponent for the relationship between lifespan and body mass is between 0.15 and 0.3. Bigger animals also expend more energy, and the scaling exponent for the relationship of resting metabolic rate (RMR) to body mass lies somewhere between 0.66 and 0.8. Mass-specific RMR therefore scales with a corresponding exponent between -0.2 and -0.33. Because the exponents for mass-specific RMR are close to the exponents for lifespan, but have opposite signs, their product (the mass-specific expenditure of energy per lifespan) is independent of body mass (exponent between -0.08 and 0.08). This means that across species a gram of tissue on average expends about the same amount of energy before it dies regardless of whether that tissue is located in a shrew, a cow, an elephant or a whale. This fact led to the notion that ageing and lifespan are processes regulated by energy metabolism rates and that elevating metabolism will be associated with premature mortality--the rate of living theory. The free-radical theory of ageing provides a potential mechanism that links metabolism to ageing phenomena, since oxygen free radicals are formed as a by-product of oxidative phosphorylation. Despite this potential synergy in these theoretical approaches, the free-radical theory has grown in stature while the rate of living theory has fallen into disrepute. This is primarily because comparisons made across classes (for example, between birds and mammals) do not conform to the expectations, and even within classes there is substantial interspecific variability in the mass-specific expenditure of energy per lifespan. Using interspecific data to test the rate of living hypothesis is, however, confused by several major problems. For example, appeals that the resultant lifetime expenditure of energy per gram of tissue is 'too variable' depend on the biological significance rather than the statistical significance of the variation observed. Moreover, maximum lifespan is not a good marker of ageing and RMR is not a good measure of total energy metabolism. Analysis of residual lifespan against residual RMR reveals no significant relationship. However, this is still based on RMR. A novel comparison using daily energy expenditure (DEE), rather than BMR, suggests that lifetime expenditure of energy per gram of tissue is NOT independent of body mass, and that tissue in smaller animals expends more energy before expiring than tissue in larger animals. Some of the residual variation in this relationship in mammals is explained by ambient temperature. In addition there is a significant negative relationship between residual lifespan and residual daily energy expenditure in mammals. A potentially much better model to explore the links of body size, metabolism and ageing is to examine the intraspecific links. These studies have generated some data that support the original rate of living theory and other data that conflict. In particular several studies have shown that manipulating animals to expend more or less energy generate the expected effects on lifespan (particularly when the subjects are ectotherms). However, smaller individuals with higher rates of metabolism live longer than their slower, larger conspecifics. An addition to these confused observations has been the recent suggestion that under some circumstances we might expect mitochondria to produce fewer free radicals when metabolism is higher--particularly when they are uncoupled. These new ideas concerning the manner in which mitochondria generate free radicals as a function of metabolism shed some light on the complexity of observations linking body size, metabolism and lifespan.

Animals↗

PubMed2005

Postglacial expansion of the southern red-backed vole (Clethrionomys gapperi) in North America.

Dynamic climatic oscillations of the Pleistocene dramatically changed the distributions of high latitude species. Molecular investigations of a variety of organisms show that processes of postglacial colonization of boreal regions were more complex than initially thought. Phylogeographical and coalescent analyses were conducted on partial sequences of the cytochrome b gene (600 bp) from 64 individuals of Clethrionomys gapperi from North Carolina, Pennsylvania, Minnesota, Idaho, Washington, British Columbia, Northwest Territories, and Alaska to test hypotheses relating to Pleistocene refugia and postglacial colonization routes. Three divergent clades (east, west, central) were identified with highest net divergence (dA = 5.2%) between the eastern and western clades. Populations from the recently deglaciated higher latitudes of Canada and Alaska are closely related to lower latitude populations of the central clade (dA = 1.2%) suggesting recent expansion from this midwestern region. No representatives from the east or west clade were found at latitudes higher than 50 degrees N, indicating that postglacial colonization occurred through a midcontinental route. The high latitude population from the Northwest Territories exhibited demographic patterns and genetic diversity consistent with a stable noncolonizing population. This population is found near the Mackenzie range, where the two continental ice sheets were believed to have coalesced. Molecular variation observed in this population may be the result of leading edge population diversifying in the continental corridor or may reflect the signal of a high latitude refugial population.

Animals↗

PubMed1975

The nature of extraversion: a genetical analysis.

A biometrical-genetical analysis of twin data to elucidate the determinants of variation in extraversion and its components, sociability and impulsiveness, revealed that both genetical and environmental factors contributed to variation in extraversion, to the variation and covariation of its component scales, and to the interaction between subjects and scales. A large environmental correlation between the scales suggested that environmental factors may predominate in determining the unitary nature of extraversion. The interaction between subjects and scales depended more on genetical factors, which suggests that the dual nature of extraversion has a strong genetical basis. A model assuming random mating, additive gene action, and specific environmental effects adequately describes the observed variation and covariation of sociability and impulsiveness. Possible evolutionary implications are discussed.

Adult↗

PubMed2000

Activity of wheat alpha-amylase inhibitors towards bruchid alpha-amylases and structural explanation of observed specificities.

Plant alpha-amylase inhibitors show great potential as tools to engineer resistance of crop plants against pests. Their possible use is, however, complicated by observed variations in specificity of enzyme inhibition, even within closely related families of inhibitors. Five alpha-amylase inhibitors of the structural 0.19 family were isolated from wheat kernels, and assayed against three insect alpha-amylases and porcine pancreatic alpha-amylase, revealing several intriguing differences in inhibition profiles, even between proteins sharing sequence identity of up to 98%. Inhibition of the enzyme from a commercially important pest, the bean weevil Acanthoscelides obtectus, is observed for the first time. Using the crystal structure of an insect alpha-amylase in complex with a structurally related inhibitor, models were constructed and refined of insect and human alpha-amylases bound to 0.19 inhibitor. Four key questions posed by the differences in biochemical behaviour between the five inhibitors were successfully explained using these models. Residue size and charge, loop lengths, and the conformational effects of a Cys to Pro mutation, were among the factors responsible for observed differences in specificity. The improved structural understanding of the bases for the 0.19 structural family inhibitor specificity reported here may prove useful in the future for the rational design of inhibitors possessing altered inhibition characteristics.

Amino Acid Sequence↗

PubMed1979

An evaluation of cellularity in various types of bone marrow specimens.

Comparisons of marrow cellularity determinations in needle biopsy sections, aspirated smears of marrow particles, and aspirated clot sections were made using the point-counting and standard visual methods of measurement. Good correlations of cellularity between biopsies and smears were obtained with the point-counting method. This occurred with either single- or multiple-observer measurements, and differed from the wide observer-to-observer variation obtained in the other comparisons. Although the optimal method for cellularity measurements is point counting by biopsy sections, the findings indicate that aspirated smears of marrow particles can be a suitable substitute for needle biopsy sections when point counting is used. This would be particularly useful in clinical settings necessitating frequent cellularity assessments. The results also show that the standard visual method of cellularity measurement is satisfactory when specimens are evaluated by one observer. The point-counting method of measurement, although the most accurate, is not as reproducible among observers as previously considered.

Biopsy, Needle↗

PubMedDate not supplied

Investigation of conjugated metabolites of 4-hydroxyandrost-4-ene-3,17-dione in patient urine by liquid chromatography-atmospheric pressure ionization mass spectrometry.

Metabolism of the anticancer drug 4-hydroxyandrost-4-ene,3,17-dione (4OHA) was studied in cancer patients by HPLC-MS-MS. 40HA was administered orally to a breast cancer patient. The drug was extensively metabolized and was excreted in the urine as the 4OHA-glucuronide, 3 alpha-hydroxy-5 beta-androstan-4,17-dione (3 alpha OHA)-sulfate (or 4-hydroxytestosterone-sulfate) and 3 alpha,17-dihydroxy-5 beta-androstan-4-one (3,17-OHA)-sulfate conjugates in the 4 hr posttreatment sample. Other metabolites include 4OHA-sulfate, 3 alpha OHA-glucuronide, and 3,17-OHA-monoglucuronide. When 4OHA was given to the prostatic cancer patients intramuscularly, different metabolites were observed as compared with the female studies. The most noticeable difference is the absence of 4OHA-sulfate in both 24 and 48 hr posttreatment urine samples. The drug was eliminated mainly as 4OHA-glucuronide, 3 alpha OHA-sulfate, and 3,17-OHA-monosulfate. Other metabolites that have been detected include 3 alpha OHA-glucuronide, 3,17-OHA-glucuronide, 3,17-OHA-disulfate, and an unknown metabolite. The variation observed in metabolism could be attributed to a different route of drug administration (oral and intramuscular) and sex difference among the patients. This study describes the utilization of HPLC-MS-MS for monitoring the 4OHA conjugates and provides the first evidence of the presence of 4OHA-sulfate and its analogs in patient urinary extracts.

Androstenedione↗

PubMed1997

Discrimination of hepatitis G virus/GBV-C geographical variants by analysis of the 5' non-coding region.

We have investigated the ability of different subgenomic fragments to reproduce the phylogenetic relationships observed between six complete genome sequences of GBV-C/hepatitis G virus (HGV). While similar relationships were observed following analysis of part of the 5' non-coding region (5'NCR), for the coding region they were not accurately reproduced for some large fragments or for the majority of fragments of 300 or 600 nucleotides. Analysis of 5'NCR sequences from a large number of isolates, including newly obtained sequences from Pakistan, Zaïre and Scotland, produced separate groupings of Asian, African and European/North American variants. These groupings are associated with specific polymorphisms in the 5'NCR, many of which were covariant and consistent with a proposed secondary structure for this region. The relatively low level of amino acid sequence variation observed between these geographically and phylogenetically defined groups of variants suggests that they are unlikely to display significant biological differences.

Base Sequence↗