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PubMed1996

Temporal and geographic variation of organochlorine residues in eggs of the common snapping turtle (Chelydra serpentina serpentina) (1981-1991) and comparisons to trends in the herring gull (Larus argentatus) in the Great Lakes basin in Ontario, Canada.

Common snapping turtle (Chelydra serpentina serpentina) eggs from five sites within the Great Lakes basin, and from a reference site in north-central Ontario were collected during 1981-1991 and analyzed for four organochlorine pesticides, polychlorinated biphenyls (PCBs) including six non-ortho PCBs, polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). The pattern of geographic variation was consistent over time in eggs with Cootes Paradise/ Hamilton Harbour and Lynde Creek eggs on Lake Ontario containing the highest concentrations and most PCDD and PCDF congeners among all sites. Eggs from Cranberry Marsh on Lake Ontario contained organochlorine concentrations similar to those from Big Creek Marsh and Rondeau Provincial Park on Lake Erie except PCDDs and PCDFs which occurred at higher concentrations and more congeners were detectable in Cranberry Marsh eggs. Concentrations of most contaminants in turtle eggs from Algonquin Park, the reference site, have significantly decreased in the past decade. Dieldrin concentrations, however, increased in Algonquin Park eggs from 1981 to 1989. Significant decreases in concentrations of hexachlorobenzene, mirex and PCBs occurred between turtle eggs collected in 1981/84 and 1989 at Big Creek Marsh and Rondeau Provincial Park, whereas there was no significant change in concentrations of p,p'-DDE and dieldrin. In Lake Ontario eggs, concentrations of PCBs, p,p'-DDE and dieldrin increased significantly between 1984 and 1991. Differences were also found in patterns of temporal variation in contamination between herring gulls (Larus argentatus) and snapping turtles which were attributed to differences in diet. Elevated and continued contamination in turtle eggs from Lake. Ontario is probably due to a combination of local sources of chemicals and consumption of large migratory fish that spawn in wetlands inhabited by these turtles.

Animals↗
PubMed2005

Polymorphism of the AHSG gene is associated with increased adipocyte beta2-adrenoceptor function.

The alpha(2) Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity. The Met/Met genotype of the common single-nucleotide polymorphism (SNP), rs4917, in the AHSG gene has been shown to be associated with reduced plasma levels as well as lower body fat. Here, we studied the association of this variation with subcutaneous adipocyte lipolysis. Ninety-three obese and nonobese healthy men were genotyped for Thr230Met, and subcutaneous adipose tissue biopsies were analyzed for lipolysis characteristics. The Met/Met genotype was associated with a marked increase of 1.5 log units in the lipolytic sensitivity to the beta2-adrenoceptor agonist terbutaline (P=0.0008) as compared with the Thr/Thr and Thr/Met genotypes. This corresponds to an approximately 35-fold increase in beta2-adrenoceptor function. The genotype effect was independent of body mass index and waist circumference. In contrast, lipolytic sensitivity to both the beta1-adrenoceptor agonist dobutamine (P=0.25) and the alpha2A-adrenoceptor agonist clonidine (P=0.54) was unaffected by the Thr230Met variation. Moreover, no difference in either maximal stimulation or inhibition of lipolysis was found between genotypes. We conclude that a common variation (Thr230Met) in the AHSG gene is associated with a marked increase in beta2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation.

Adipocytes↗
PubMed2004

Congenital cystic adenomatoid malformation connected to an extralobar pulmonary sequestration in the contralateral chest: common origin?

Extralobar pulmonary sequestration (ELS) and congenital cystic adenomatoid malformation have been reported to coexist in several variations. This suggests a common embryologic origin. A 6-month-old boy presented with a history of recurrent pneumonias. The patient was diagnosed with a right lower lobe congenital cystic adenomatoid malformation (CCAM) and a left lower lobe ELS/CCAM. The diagnosis was made with the aid of a multidetector computed tomography (CT). Three-dimensional CT reconstruction showed the presence of a right lower lobe CCAM, a left lower ELS with an aberrant arterial supply from the celiac axis, and possible venous drainage into the right CCAM. The patient underwent a right thoracotomy. Intraoperatively, the lesions were discovered to be connected by a band of tissue. The right lower lobe CCAM and the left ELS were removed from the right chest. Histologic analysis confirmed the presence of a CCAM within the right lower lobe. The ELS had involvement of a type II CCAM within the sequestration. The connection between the right CCAM and left ELS/CCAM showed an anomalous conducting airway, anomalous vein, and anomalous artery connecting the 2 lesions. The authors present the first case of a CCAM connected to an ELS/CCAM in the contralateral hemithorax. The unique anatomic configuration of these lesions suggests a common embryologic origin of ELS and CCAM.

Bronchopulmonary Sequestration↗
PubMed1999

Geographic variations in the rates of operative procedures involving the shoulder, including total shoulder replacement, humeral head replacement, and rotator cuff repair.

BACKGROUND: Although geographic variations in the rates of orthopaedic procedures have been well documented, considerable controversy remains regarding the factors that drive these variations, particularly the role of the availability of orthopaedic surgeons. Moreover, little attention has been specifically focused on variations in the rates of commonly performed shoulder procedures. METHODS: The current study documents state-to-state variations in the rates of total shoulder replacement, humeral head replacement, and rotator cuff repair and examines factors that might account for these variations. The regional incidences of these three procedures were analyzed with use of the Health Care Financing Administration Medicare database (MEDPAR, 1992). The rates were age-adjusted, and variations were measured with use of high:low ratios, variation coefficients, and systematic components of variation. Potential causes of variation were analyzed with use of Spearman and partial correlations as well as with Poisson regression. RESULTS: Rates for the three procedures that were studied varied from one state to another by as much as tenfold. Humeral head replacement had the lowest rate of variation according to all three measures. All three procedures were performed less often in states that were more densely populated. With the numbers available for study, no consistent, significant relationship was found between the density of orthopaedists and shoulder surgeons and the rates of any procedure. CONCLUSIONS: The striking variations that were noted for these commonly performed procedures showed that there is a clear need for well designed clinical research to further define the factors that account for the variations and to examine the effectiveness and appropriate indications for the procedures.

Aged↗
PubMed2000

Seasonal variation of MXR and stress proteins in the common mussel, Mytilus galloprovincialis.

The accumulation of heat-shock HSP70 and MXR proteins in the digestive gland and gills respectively of the mussel (Mytilus galloprovincialis) has been examined in individuals collected monthly during 1 year from the mariculture areas located in the Ebro Delta (NW Spain). Both proteins were visualised and semi-quantified by western blot using commercially available monoclonal antibodies and subsequent image analysis. Two HSP-related bands of Mr 72 and 78 kDa and two MXR proteins of Mr 230 and 130 kDa were detected and their seasonal variations in expression levels recorded. A significant correlation between HSP70 and MXR expression was obtained, the maximum protein accumulation being detected during the summer period. These two parameters were also significantly correlated to water temperature at sample sites. These results suggest either a direct role of temperature in protein expression or an indirect role driven by food availability and growth.

Journal Article↗
PubMed2003

Genetic and ecological correlates of intraspecific variation in pitviper venom composition detected using matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) and isoelectric focusing.

The ability to detect biochemical diversity in animal venoms has wide-ranging implications for a diverse array of scientific disciplines. Matrix-assisted laser desorption time-of-flight mass spectrometry (and, for comparative purposes, isoelectric focusing) were used to characterize venoms from a geographically diverse sample of Trimeresurus stejnegeri ( n < 229) from Taiwan. Previously unrealized levels of heterogeneity were detected in venom phospholipase A(2) isoforms (PLA(2)) and in whole venom profiles. Geographic variation in venom was primarily between Taiwan and two Pacific islets. Despite the common assumption that venom variation is a product of neutral molecular evolution, statistical testing failed to link venom variation with phylogenetic descent convincingly. Instead, pronounced differences in venom composition may be the product of natural selection for regional diets or of independent founder effects. More data are required on the functional differences between the isoforms to distinguish between these alternatives.

Animals↗
PubMed2005

In search of genes involved in neurodegenerative disorders.

Dissecting the genetics of Alzheimer's disease (AD) and Parkinson's disease (PD) has contributed significantly to our understanding of the pathogenesis of neurodegeneration in these two complex disorders. For AD, three highly penetrant genes (amyloid precursor protein (APP, PSEN1 and PSEN2) and one susceptibility gene (APOE) have been identified. For PD, seven genes (SNCA, Parkin, UCHL1, NR4A2, DJ1, PINK1 and LRRK2) have been found. These genes explain only a small proportion of AD and PD patients and are mostly associated with an early onset presentation of the disease. APOE remains the only common gene, which increases the risk of both rare early and late onset AD. The ongoing challenge is to unravel the genetics of the most frequent forms of these complex disorders. In the present paper, we briefly review the state of the art in the genetics of AD and PD. We also discuss the prospects of finding new genes associated with common forms of these diseases in light of two hypotheses concerning the genetic variation of complex diseases: common disease/common variants and common disease/rare variants.

Alzheimer Disease↗
PubMed1999

Comparison of the dynamics of bile emptying by quantitative hepatobiliary scintigraphy before and after cholecystectomy in patients with uncomplicated gallstone disease.

PURPOSE: Quantitative hepatobiliary scintigraphy, a noninvasive method frequently used to diagnose several biliary tract disorders, shows abnormalities in bile secretion and outflow. It is well known that there are wide variations in the normal pattern of bile emptying, but the effect of cholecystectomy on the bile flow has not yet been investigated. The goal of the current study was to examine the dynamics and normal variations of bile flow by quantitative hepatobiliary scintigraphy before and after cholecystectomy in a group of patients with uncomplicated gallstone disease. METHODS: Twenty patients were evaluated before and after cholecystectomy through cholecystokinin octapeptide-augmented quantitative hepatobiliary scintigraphy, and quantitative parameters of bile emptying (Tmax: time to peak activity, T1/2: half-emptying time before and after cholecystokinin octapeptide and duodenum appearance time) were determined and then compared. RESULTS: Before operation, the bile outflow displayed wide variations, with a moderately delayed common bile duct emptying time in some patients. After cholecystectomy, the T1/2 of the common bile duct decreased significantly when compared with the preoperative status, with only minor patient-to-patient variation, indicating uniformly faster bile emptying (common bile duct T1/2 before and after operation: 30.5 +/- 14.8 and 18.8 +/- 2.6 min, respectively). Cholecystokinin octapeptide administration caused rapid bile outflow from the common bile duct, with a significant decrease in the T1/2 parameters before and after cholecystectomy. CONCLUSIONS: In patients with their gallbladders in situ, the bile emptying rate showed wide variations and may be moderately slow without distal common bile duct obstruction. After cholecystectomy, the rate of bile emptying accelerated and showed only minor variations, thereby increasing the sensitivity of quantitative hepatobiliary scintigraphy for showing partial biliary obstruction.

Adult↗
PubMed2007

Genetic and environmental determinants of circulating resistin level in a community-based sample.

OBJECTIVE: Resistin is a hormone secreted by adipose tissue, monocytes, bone marrow, and other tissues. It was also proclaimed as an important link between obesity and diabetes. The main objective of this study was to elucidate the contribution of a number of endogenous factors, such as sex, age, obesity characteristics, and genetic effects to the production of resistin in apparently healthy individuals. We also tested the possible relationships between circulating levels of resistin and other adipokines (leptin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)). MEASUREMENTS: The plasma levels of studied adipokines were determined by enzyme-linked immunoassay in pedigree-based sample (n = 616), and subjected to model-based quantitative genetic analysis. RESULTS: Resistin levels were significantly higher in women than in men (3.60 +/- 2.53 vs 3.15 +/- 2.48 ng/ml, P < 0.001), and varied independently of age in either sex. Statistical-genetic analysis revealed significant familial correlations (P < 0.01) for resistin. Adjusted for covariates, 66.38 +/- 10.28% of the resistin variation was attributable to putative genetic factors. A relatively small portion of the resistin variation (11.54 +/- 5.77%) was attributable to sharing a common household environment. The remaining variation, 22.12 +/- 17.69% was due to random environmental (i.e., unmeasured non-additive genetic) effects. The results of our analysis showed modest significant correlation of resistin with TNF-alpha and IL-6, and only in some groups; thus, while resistin was correlated with TNF-alpha in men, the correlation with IL-6 was significant only in the post-menopausal women group. CONCLUSIONS: Our observations indicate that resistin is strongly influenced by genetic factors. The high heritability estimates for resistin concentrations clearly suggest the continuing need for further molecular genetic investigations.

Adolescent↗
PubMed2004

Common mental disorders and ethnicity in England: the EMPIRIC study.

BACKGROUND: There is little population-based evidence on ethnic variation in the most common mental disorders (CMD), anxiety and depression. We compared the prevalence of CMD among representative samples of White, Irish, Black Caribbean, Bangladeshi, Indian and Pakistani individuals living in England using a standardized clinical interview. METHOD: Cross-sectional survey of 4281 adults aged 16-74 years living in private households in England. CMD were assessed using the Revised Clinical Interview Schedule (CIS-R), a standardized clinical interview. RESULTS: Ethnic differences in the prevalence of CMD were modest, and some variation with age and sex was noted. Compared to White counterparts, the prevalence of CMD was higher to a statistically significant degree among Irish [adjusted rate ratios (RR) 2.09, 95% CI 1.16-2.95, p = 0.02] and Pakistani (adjusted RR 2.38, 95 % CI 1.25-3.53, p = 0.02) men aged 35-54 years, even after adjusting for differences in socio-economic status. Higher rates of CMD were also observed among Indian and Pakistani women aged 55-74 years, compared to White women of similar age. The prevalence of CMD among Bangladeshi women was lower than among White women, although this was restricted to those not interviewed in English. There were no differences in rates between Black Caribbean and White samples. CONCLUSIONS: Middle-aged Irish and Pakistani men, and older Indian and Pakistani women, had significantly higher rates of CMD than their White counterparts. The very low prevalence of CMD among Bangladeshi women contrasted with high levels of socio-economic deprivation among this group. Further study is needed to explore reasons for this variation.

Adolescent↗
PubMed2001

Assessment of genetic structure within and among Bulgarian populations of the common ash (Fraxinus excelsior L.).

We analysed genetic variation within and between populations of the common ash from Bulgaria in order to extract biological information useful in the context of conservation management of eastern European genetic resources of noble hardwood species. A total of 321 trees from three regions of Bulgaria were typed at six highly polymorphic microsatellite loci. Analysis of within-population inbreeding suggests an upper boundary value of 2.7% for the selfing rate. Significant spatial genetic structure consistent with models of isolation by distance was detected within four out of 10 populations as well as among populations. Estimates of neighbourhood size in the range 38-126 individual trees were obtained based on spatial genetic structure analyses at either the intrapopulation or interpopulation level. Differentiation among populations explained only about 8.7% of total genetic diversity. These results are discussed in comparison with data from social broad-leaved species such as oak and beech.

Alleles↗
PubMed2004

Patterns of tooth crown size and shape variation in great apes and humans and species recognition in the hominid fossil record.

It has been suggested that patterns of craniodental variation in living hominids (Gorilla, Homo, Pan, and Pongo) may be useful for evaluating variation in fossil hominid assemblages. Using this approach, a fossil sample exhibiting a pattern of variation that deviates from one shared among living taxa would be regarded as taxonomically heterogeneous. Here we examine patterns of tooth crown size and shape variation in great apes and humans to determine 1) if these taxa share a pattern of dental variation, and 2) if such a pattern can reliably discriminate between samples that contain single species and those that contain multiple species. We use parametric and nonparametric correlation methods to establish the degree of pattern similarity among taxa, and randomization tests to assess their statistical significance. The results of this study show that extant hominids do not share a pattern of dental size variation, and thus these taxa cannot be used to generate expectations for patterns of size variation in fossil hominid species. The hominines (Gorilla, Homo, and Pan) do share a pattern of shape variation in the mandibular dentition; however, Pongo is distinct, and thus it is unclear which, if either, pattern should be expected in fossil hominids. Moreover, in this case, most combined-species samples exhibit patterns of shape variation that are similar to those for single hominine species samples. Thus, although a common pattern of shape variation is present in the mandibular dentition, it is not useful for recognizing taxonomically mixed paleontological samples.

Animals↗
PubMed2026

Integrating multi-ancestry common and rare variant mapping accelerates therapeutic target discovery.

Integrating human genetics into therapeutic discovery accelerates drug development. However, ancestral biases in historical cohorts have left critical functional variation largely uncharted. Here, we leverage the diverse NIH All of Us Research Program to conduct comprehensive common- and rare-variant association analyses for 624 quantitative traits across 369,655 ancestrally diverse individuals. We identified 6,181 genome-wide significant locus-trait associations (526 novel) and 416 gene-trait associations (105 novel) via rare-variant burden testing. By integrating fine-mapping with computational variant-effect predictors, we systematically prioritized rare, likely causal variants driving these signals. Jointly modeling common and rare variation with protein-class annotations significantly improved the identification of known drug targets compared to common-variant analysis alone. Notably, we identified NRG4 as a high-confidence candidate therapeutic target for preserving kidney function. Our findings demonstrate that characterization of rare and common variation across diverse populations enhances causal gene discovery and identifies novel, actionable therapeutic targets.

Journal Article↗
PubMed2005

Does rainfall explain variation in leaf morphology and physiology among populations of red ironbark (Eucalyptus sideroxylon subsp. tricarpa) grown in a common garden?

We investigated adaptation of leaf morphology and physiology of red ironbark (Eucalyptus sideroxylon Cunn. Ex. Wools subsp. tricarpa L.A.S. Johnson) in a common garden experiment. Fifteen populations, representing a rainfall range of 500 to 1055 mm per annum at the sites of seed collection, were grown at the same site. Because environmental variables other than rainfall did not vary significantly among populations, we were able to test if leaf morphology and physiology were related to seed-source rainfall. There were large differences among and within populations in all measured variables. Most univariate relationships with seed-source rainfall were not significant. Notable exceptions were the weak positive correlation of specific leaf area with seed-source rainfall-consistent with expectations-and the weak negative correlation of photosynthesis and stomatal conductance with seed-source rainfall-the opposite of what we predicted. In many cases, populations collected from sites of similar rainfall differed greatly in leaf morphology and physiology. Principal component analysis (PCA) reduced the 13 input variables to five principal components (PC) explaining 73.0% of the total variance in the original data. Some of the PC axes could be interpreted in terms of adaptation to drought (i.e., to seed-source rainfall), but relationships of accumulated variables (the PC axes) with seed-source rainfall were significant for only one PC axis. Hence, among red ironbark populations grown in a common garden, there was significant genetic variation in leaf morphology and physiology, but for most traits, this variation was unrelated to rainfall at the site of seed collection. This study adds to a growing body of common garden literature showing weak within-species relationships of leaf morphology and physiology with seed-source rainfall, in contrast to the consistently stronger relationships among species growing at different points along broad environmental gradients.

Eucalyptus↗
PubMed1989

Relationships between human parotid saliva lysozyme lactoferrin, salivary peroxidase and secretory immunoglobulin A in a large sample population.

Saliva antimicrobial proteins may interact in a common system for host defence. This study applied multivariate analysis as a means of describing inter-person variation in that system. Samples of stimulated parotid saliva were obtained from 198 subjects. Flow rate was determined, and assays run for total protein, lysozyme, lactoferrin, salivary peroxidase and secretory IgA. Correlation and principal components analysis were used to define the relationships between proteins; cluster analysis was used to identify persons with similar protein concentration profiles. All proteins were significantly correlated at p less than 0.002 (r = 0.20-0.52). Principal components analysis identified a major axis of common variation, defined by lysozyme and salivary peroxidase, and a second axis, defined by secretory IgA. Lactoferrin was associated with both axes. Seven major groupings were obtained by cluster analysis; these were significantly different at p less than 0.001. Such groupings may prove useful in comparing the antimicrobial properties of saliva samples.

Adolescent↗
PubMed1998

Variations in standardized hospital mortality rates for six common medical diagnoses: implications for profiling hospital quality.

OBJECTIVES: The authors determined whether standardized hospital mortality rates varied for six common medical diagnoses. METHODS: The retrospective cohort study included 89,851 patients aged 18 years and older discharged from 30 hospitals in a large metropolitan area in 1991 to 1993 with a principal diagnosis of acute myocardial infarction, congestive heart failure, pneumonia, stroke, obstructive lung disease, or gastrointestinal hemorrhage. For each hospital, standardized mortality ratios (observed/predicted mortality) were determined using validated risk-adjustment models that were based on clinical data elements abstracted from patients' hospital records. Hospitals also were categorized into quintiles on the basis of standardized mortality ratios. Correlations between standardized mortality ratios and agreement between quintile rankings were determined for each pair of diagnoses. RESULTS: Correlations between hospital-standardized mortality ratios for individual diagnoses were generally weak. For the 15 possible pairs of diagnoses, Pearson coefficients ranged from -0.10 to 0.43; only six were 0.30 or greater. Agreement between hospital quintile rankings was also generally low, with weighted kappa values ranging from -0.12 to 0.42. Three of 15 kappa values were less than 0 (ie, agreement lower than chance), and only four exceeded 0.20, the threshold for "fair" agreement. Although simulated analyses found that random variation and relatively low hospital volumes accounted for some of the difference in standardized mortality ratios for diagnoses, a large proportion of the difference remained unexplained. CONCLUSIONS: Standardized hospital mortality rates varied for six diagnoses that likely are managed by similar practitioners. Although variability may be decreased by restricting analyses to hospitals with large volumes, the findings indicate that for many hospitals, diagnosis-specific mortality rates may be an inconsistent measure of hospital quality, even when data are aggregated for multiple years.

Adolescent↗
PubMed2026

Shared genetic basis and structure of syndromic and normal facial variation.

The question of how gene mutations of large effect and common variants of small effect relate to phenotypic variation dates from the origins of genetics. Mendelian diseases result from rare germline variants with major effects, while complex traits are associated with multiple, mostly common variants of small effect. High-dimensional phenotypes, such as facial shape, can shed new light on this age-old dichotomy, as their variation can be characterized in terms of directions in multivariate morphospace. Within such spaces, do Mendelian disease mutations move phenotypes along the same directions as common variants, or do they forge new directions that diverge from the common structure of background variation? Here, we analyze facial shape variation for 66 syndromes, quantify multivariate axes of facial shape variation for each syndrome, and test whether common genetic variants in cohorts of non-syndromic subjects are associated with phenotypic position along these same axes. We find that syndromic facial shape generally follows the background variance-covariance structure of facial shape in the general population. Furthermore, syndromic probands' unaffected relatives have subtle facial morphology resembling the syndromes of their affected relatives. These results suggest that Mendelian disease variants act on facial shape in ways similar to common variants. Syndromic probands with higher "severity" likely occur on genetic backgrounds with higher cumulative severity of common variants for each syndromic axis. These findings position Mendelian diseases at extremes along phenotypic continua that exist in the background population rather than as qualitatively different phenotypes distinct from the overall structure of normal human phenotypic variation.

Humans↗