Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “common variation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1977

An estimate of the amount of genetic variation in the common mussel Mytilus edulis.

Allozyme variation in a population of the common mussel Mytilus edulis in Mumbles, South Wales, has been studied by starch gel electrophoresis. On the basis of data obtained for 34 loci, we estimate the proportion of loci polymorphic to be 30%. Using only the 29 loci for which individual genotypes can be accurately typed, the average heterozygosity is estimated to be 9.5 +/- 3.6%. The calculated expected average heterozygosity based on Hardy-Weinberg expectations is identical with the observed value. Allele frequency data at six polymorphic loci are given for several other British populations. There is no significant geographic heterogeneity. The results are discussed in relation to genetic adaptive strategies and are shown to be inconsistent with the predictions of the neutral hypothesis.

Alleles↗
PubMed2003

Variants of the CD40 ligand gene are not associated with increased susceptibility to tuberculosis in West Africa.

Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5' regulatory sequences of the gene. Six single nucleotide polymorphisms (SNPs) and a 3' microsatellite were genotyped in 121 tuberculosis patients and their available parents. No association with tuberculosis was detected for these variants using a transmission disequilibrium test, although one SNP at -726 showed some evidence of association in males. This finding, however, did not replicate in a separate case control study of over 1,200 West African individuals. We conclude that common genetic variation in TNFSF5 is not likely to affect tuberculosis susceptibility in West Africa and the linkage observed in this region is not due to variation in TNFSF5.

Africa, Western↗
PubMedDate not supplied

MR arthrography of the shoulder: variants and pitfalls.

Use of magnetic resonance arthrography to evaluate pathologic conditions of the shoulder is becoming widespread. However, normal anatomy or anatomic variations can cause interpretive errors. The most common variations occur at the origins of the glenohumeral ligaments (GHLs) and the insertion of the joint capsule. Among the GHL variants, common origin of the superior and middle ligaments is the most frequent followed by thinning, thickening, or absence of a ligament, most often the middle one. Absence or thinning of one ligament is sometimes associated with thickening of another or changes in the size and shape of the anterior capsular recesses. Common normal variants of the labrum include foramen sublabrum (detachment of the anterosuperior labrum from the glenoid margin) and the Buford complex (absence of the anterosuperior labrum in association with a thick middle GHL). Pitfalls related to the arthrographic technique include (a) visualization of a deep sulcus between the insertion of the long head of the biceps tendon and the superior labrum and (b) an apparent type III capsular insertion due to overdistention of the capsule by injected contrast material.

Arthrography↗
PubMed2006

Analysis of polymorphisms of the interleukin-18 gene in type 1 diabetes and Hardy-Weinberg equilibrium testing.

Recently, the interleukin-18 cytokine gene (IL18) was reported to be associated with type 1 diabetes. In the present report, we calculated that the reported genotypes of the two 5' region/promoter single nucleotide polymorphisms (SNPs), -607 (C-->A) (rs1946518) and -137 (G-->C) (rs187238), were not in Hardy-Weinberg equilibrium (HWE). We therefore investigated the association of the -607 and -137 SNPs in a U.K. type 1 diabetic Caucasian case-control collection (1,560 case and 1,715 control subjects tested at -607 and 4,323 case and 4,610 control subjects tested at -137) as well as a type 1 diabetic Caucasian collection comprised of families of European ancestry (1,347 families tested at -137 and 1,356 families tested at -607). No evidence for association with type 1 diabetes was found, including for the -607 A/A and C/A genotypes. To evaluate whether common variation elsewhere in the gene was associated with disease susceptibility, we analyzed eight IL18 tag SNPs in a type 1 diabetic case-control collection (1,561 case and 1,721 control subjects). No evidence for association was obtained (P = 0.11). We conclude that common allelic variation in IL18 is unlikely to contribute substantially to type 1 diabetes susceptibility in the populations tested and recommend routine application of tests for HWE in population-based studies for genetic association.

Alleles↗
PubMed1975

Surgical anatomy of the mesocaval shunt.

Having encountered wide variations in the surgical trunk of the superior mesenteric vein and its arterial relationships during the performance of mesocaval shunts, we believed it would be rewarding to evaluate this vessel in a series of 36 cadavers. In two of these 36 instances, we determined that the anatomic findings precluded the performance of a mesocaval shunt. In ten other instances, even though a shunt could be performed, a knowledge of these variations could prevent operative complications. The most common variation was a bifurcation of the superior mesenteric vein at or proximal to the site of the surgical trunk. Another variation which could cause operative difficulties was unusual positions of the superior mesenteric artery and its major branches in relation to the vein at the level of the surgical trunk. A knowledge of these variations in the surgical anatomy of the superior mesenteric vein should make mesocaval shunts easier and safer to perform.

Humans↗
PubMed2004

A genome-wide survey of segmental duplications that mediate common human genetic variation of chromosomal architecture.

Recent studies have identified a small number of genomic rearrangements that occur frequently in the general population. Bioinformatics tools are now available for systematic genome-wide surveys of higher-order structures predisposing to such common variations in genomic architecture. Segmental duplications (SDs) constitute up to 5 per cent of the genome and play an important role in generating additional rearrangements and in disease aetiology. We conducted a genome-wide database search for a form of SD, palindromic segmental duplications (PSDs), which consist of paired, inverted duplications, and which predispose to inversions, duplications and deletions. The survey was complemented by a search for SDs in tandem orientation (TSDs) that can mediate duplications and deletions but not inversions. We found more than 230 distinct loci with higher-order genomic structure that can mediate genomic variation, of these about 180 contained a PSD. A number of these sites were previously identified as harbouring common inversions or as being associated with specific genomic diseases characterised by duplication, deletions or inversions. Most of the regions, however, were previously unidentified; their characterisation should identify further common rearrangements and may indicate localisations for additional genomic disorders. The widespread distribution of complex chromosomal architecture suggests a potentially high degree of plasticity of the human genome and could uncover another level of genetic variation within human populations.

Chromosomes, Human↗
PubMed2006

Genetic and environmental determinants of variation of soluble adhesion molecules.

In our research we examined the contribution of putative genetic sources on interindividual variation and cross-sectional correlations of several adhesion molecules, including intracellular (ICAM-1) and vascular cell adhesion molecules (VCAM-1) and E-selectin, in a population-based sample of ethnically homogeneous families of European origin. The plasma levels of these molecules were measured in 947 apparently healthy individuals from 217 nuclear families. Quantitative statistical-genetic analysis implementing the model fitting technique revealed significant parent/offspring and sibling correlations (p < 0.01) for all three molecules. The putative genetic effects explained 55.2 +/- 7.2% (VCAM-1), 63.3 +/- 7.5% (ICAM) and 63.8 +/- 8.1% (E-selectin) of the variation. Common family environmental factors also significantly influenced the variation of E-selectin (13%) and VCAM-1 (28.6%). The main results of our bivariate analysis showed that the observed phenotypic correlations between ICAM-1 and VCAM-1, and between ICAM-1 and E-selectin, were mostly attributable to shared environmental factors (r(E)= 0.896 and 0.737, respectively; p < 0.01). However, the correlation between VCAM-1 and E-selectin was likely caused by common genetic effects (r(G)= 0.334, p < 0.05). Our results show that familial clustering of adhesion molecules is likely due to strong genetic effects, supplemented with shared environmental factors.

Adolescent↗
PubMed2005

Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene.

Rare mutations in the glucokinase (GCK) gene cause fasting hyperglycemia and considerably influence birth weight when present in a mother or her offspring. The role of common variation of GCK is uncertain. A polymorphism at position -30 of the GCK beta-cell-specific promoter, present in 30% of the population, has been variably associated with type 2 diabetes and diabetes-related quantitative traits. Using 1,763 U.K. Caucasian normoglycemic adult subjects, we demonstrated that the A allele at GCK(-30) is associated with a 0.06-mmol/l increase in fasting plasma glucose (FPG) (P = 0.003). The A allele was also associated with an increase in FPG in 755 women who were 28 weeks pregnant (0.075 mmol/l, P = 0.003). We then went on to analyze the effect of GCK(-30) on birth weight using 2,689 mother/child pairs. The presence of the A allele in the mother was associated with a 64-g (25-102 g) increase in offspring birth weight (P = 0.001). We did not detect a fetal genotype effect. The increase in offspring birth weight in the 30% of mothers carrying an A allele at GCK(-30) is likely to reflect an elevated FPG during pregnancy. This study establishes that common genetic variation, in addition to rare mutations and environmental factors, can affect both FPG and birth weight.

Adult↗
PubMed2006

Comprehensive association testing of common mitochondrial DNA variation in metabolic disease.

Many lines of evidence implicate mitochondria in phenotypic variation: (a) rare mutations in mitochondrial proteins cause metabolic, neurological, and muscular disorders; (b) alterations in oxidative phosphorylation are characteristic of type 2 diabetes, Parkinson disease, Huntington disease, and other diseases; and (c) common missense variants in the mitochondrial genome (mtDNA) have been implicated as having been subject to natural selection for adaptation to cold climates and contributing to "energy deficiency" diseases today. To test the hypothesis that common mtDNA variation influences human physiology and disease, we identified all 144 variants with frequency >1% in Europeans from >900 publicly available European mtDNA sequences and selected 64 tagging single-nucleotide polymorphisms that efficiently capture all common variation (except the hypervariable D-loop). Next, we evaluated the complete set of common mtDNA variants for association with type 2 diabetes in a sample of 3,304 diabetics and 3,304 matched nondiabetic individuals. Association of mtDNA variants with other metabolic traits (body mass index, measures of insulin secretion and action, blood pressure, and cholesterol) was also tested in subsets of this sample. We did not find a significant association of common mtDNA variants with these metabolic phenotypes. Moreover, we failed to identify any physiological effect of alleles that were previously proposed to have been adaptive for energy metabolism in human evolution. More generally, this comprehensive association-testing framework can readily be applied to other diseases for which mitochondrial dysfunction has been implicated.

Body Mass Index↗
PubMed1992

Individual susceptibility to toxicity.

Individual variation in susceptibility to chemical toxicity may be due to differences in toxicokinetic patterns or effect modification. Well-documented interspecies genetic differences in susceptibility to chemicals had lead to studies of such variation also within species. Epidemiological evidence now suggests that common variations, particularly in the P-450 enzymes, may play a major role in determining individual susceptibility to chemically-induced disease. Physiologic factors are involved in the particular susceptibility of the fetus, the newborn, and the old. Constitutional susceptibility is also affected by acquired conditions, including chronic disease, such as diabetes mellitus. Perhaps the most complex area relates to the increase in vulnerability caused by previous or contemporary exposure to other factors, thus eliciting, e.g., synergistic effects. Although amply demonstrated by experimental studies, epidemiological or clinical confirmation is generally lacking. One hypothesis suggests that a chemical exposure may affect the reserve capacity of the body, though not resulting in any immediate adverse effect. Subsequently, the body becomes unable to compensate for an additional stress, and toxicity then develops. Epidemiological approaches are available and need to be expanded. Research in this area has potential ethical implications which should be dealt with in an open, informed forum.

Age Factors↗
PubMed2004

Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study.

BACKGROUND: Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD. METHODS AND RESULTS: We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2, P=0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0, P=0.004). CONCLUSIONS: Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.

Cohort Studies↗
PubMed2003

Chronoecoepidemiology of "strain": infradian chronomics of urinary cortisol and catecholamines during nightly exposure to noise.

This meta-analysis of published data (Noise Health 5 (2002) 35 and 47) summarizing a survey for 40 days of the nightly excretion of urinary free cortisol, epinephrine and norepinephrine validates a circaseptan cortisol pattern anticipated and reported earlier for cortisol, here not detected for the catecholamines. We also quantify a circadecan (about 10-day) variation in nightly norepinephrine excretion, but not in the excretion of the other two hormones examined. About 4.2-day variations, common to norepinephrine and epinephrine, and an about 4.7-day variation in cortisol await further scrutiny, since these components were not anticipated. Infradian characteristics are quantified time-microscopically and differences among infradian aspects of the spectral element of endocrine chronomes (time structures; from chronos, time and nomos, rule) are demonstrated. Chronomics, the cartography of chronomes, reveals that "stress hormones" need to be examined separately in a budding chronoepidemiology seeking to detect how humans interact, mostly for better, sometimes for worse, with the undesirable features of the technology they create and of its consequences, such as aircraft noise.

Activity Cycles↗
PubMed2006

A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.

The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.

Genetic Predisposition to Disease↗
PubMed1997

Slight sequence variations of a common fold explain the substrate specificities of tRNA-guanine transglycosylases from the three kingdoms.

tRNA-guanine transglycosylases (TGTs) are the enzymes catalyzing the base exchange required for the synthesis of the modified bases derived from 7-deazaguanine in prokaryotic, archaebacterial, and eukaryotic tRNAs. Unlike the eukaryotic and archaebacterial enzymes, the prokaryotic TGTs have been clearly identified and highly characterized both biochemically and structurally. The recent occurrence in sequence databases of archaebacterial and eukaryotic proteins homologous to the prokaryotic TGTs reveals that all TGTs unexpectedly adopt a common fold. Observed sequence variations at the active site correlate well with their specificities for the various 7-deazaguanine derivatives and the total conservation of the catalytic residues strongly favors a common catalytic mechanism for all TGTs.

Amino Acid Sequence↗
PubMed1976

The remodeling of the edentulous mandible.

In a sample of mandibles having complete or nearly complete loss of dentition, the left half of each mandible was serially sectioned. The entire perimeter of each section was analyzed for the distribution of resorptive and depository periosteal surfaces, and from this information, the fields of remodeling were mapped for the mandible as a whole. The most common patterns of combined resorption-deposition and the range of variations were then determined. The over-all distribution of remodeling fields in the edentulous mandible differs markedly from that in the young, growing mandible. In most of the edentulous specimens, the surface of the basal bone on both the medial and lateral sides of the corpus is of a depository nature. The overlying alveolar regions on both the lingual and buccal sides, however, are characteristically resorptive. Significantly, the placement of the reversal line between the alveolar resorptive and the basal depository areas is much lower (i.e., at the level of the mental foramen) on the buccal side. Except for its inferior part, the lateral side of the ramus tends to be largely resorptive in character, and the posterior half of the lingual side also tends to be resorptive. Unlike the child's mandible, the posterior border of the ramus is resorptive, and the posteroanterior dimension of the ramus (not the whole mandible) becomes reduced and narrowed in conjunction with resorption along the anterior border. However, the amount removed from the anterior ramus is actually added to the dimension of the corpus, which becomes longer. Further, removal from the posterior ramus border does not affect the over-all length of the mandible unless condylar reduction is also involved. Also, over-all arch length is not decreased, because the surface of the mental protuberance is retained as a depository type of field (or at least does not become actively resorptive). The corpus-ramus angle (not gonial angle) is increased in the antegonial region. Because of the opening of this angle, over-all mandibular length as well as arch length is increased. In about half of the specimens, arch width was not decreased, because the lateral side of the corpus is usually of a depository nature. Notching of the anterior side of the condylar neck and the inferior part of the anterior ramus border is associated with resorptive fields in these regions, changes that are presumed to be a consequence of pressure contacts made with the articular tubercle and the maxillary tuberosity, respectively, in conjunction with a forward rotation of the whole mandible. The inferior direction of corpus realignment relative to the basal part of the ramus also increases the notching effect in the antegonial region, an effect augmented by the presence of the resorptive field in the notch itself. Certain specific variations commonly occur in several major regions of the mandible on both the lateral and medial sides...

Alveolar Process↗
PubMed1990

Continuum analysis of common branching patterns in the human arch of the aorta.

A model is proposed for describing common variations in the arrangement of branches on the arch of the human aorta, and the model is used to analyze data from 123 human arches. The analysis allows the observed variations to fall freely along a continuous spectrum, rather than be confined to discrete categories as is commonly done at present. The results thus describe these variations in a more natural way and throw some new light on their likely source.

Aorta, Thoracic↗
PubMedDate not supplied

The curve of the cervical spine: variations and significance.

OBJECTIVE: To review the literature regarding the curve of the cervical spine in normal and injured persons, emphasizing common variations in cervical curvature and their possible clinical significance. DATA SOURCE: A MEDLINE literature search of the English-language, human literature was performed using multiple search strategies relevant to radiography, posture, lordosis, injury, diagnosis and prognosis of the cervical spine (MESH: cervical vertebrae). Additionally, article bibliographies were searched for further relevant articles. No publication time limit was imposed. STUDY SELECTION: Articles were identified by the author as being directly relevant to the objective and scope of this review. DATA EXTRACTION: Data was extracted as presented in each original article. DATA SYNTHESIS: The articles reviewed indicate that a wide range of normal exists in the posture and configuration of the cervical spine. Although kyphotic angulation and straightening or reversal of cervical lordosis are commonly seen following trauma, they may be normal variants. Muscle spasm is a widely used explanation for these variations when seen in patients with pain or trauma. Kyphotic angulation is often associated with posterior ligamentous injury of a motion segment. Prognostic significance of these variations is claimed by some authors. CONCLUSION: There is little evidence to support the contention that altered cervical curvatures are of prognostic significance. Although kyphotic angulation is associated with anterior subluxation (hyperflexion sprain), it is not a reliable diagnostic criterion for that condition. It is reasonable to assume that straightening or reversal of a previously lordotic cervical curve is the result of muscular spasm, but more specific interpretation is not supported by the literature. More study is needed to characterize the specific dynamics and etiologies involved in the determination of cervical spine configuration.

Cervical Vertebrae↗
PubMed1979

Anatomical studies of a boy trisomic for the distal portion of 13q.

A boy trisomic for the distal portion of 13q was dissected in detail and compared to 8 cases of complete trisomy 13 previously studied in our laboratory. The comparison shows that the partial trisomy 13q case did not correspond well to a muscle phenotype based on 6 variations common trisomy 13, but rather to a larger muscle phenotype that included variations less frequently observed in complete trisomy 13. Additional cases of partial trisomy 13 must be studied before these findings can be related to specific portions of chromosome 13.

Abnormalities, Multiple↗