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At least 451 records · Page 25Linked to original sources
PubMed1997

Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus.

Defining the genetic determinants of NIDDM requires evidence from several complementary approaches, including both linkage and association analyses using both discrete phenotypes and intermediate quantitative traits. We tested for association between common genomic variation in three genes that map to chromosome 7q21-q22 and quantitative traits related to NIDDM in a sample of Oji-Cree. We found that a common genomic variation in codon 148 (alanine or glycine) of the paraoxonase-2 gene (PON2) demonstrated a significant association with a variation in fasting plasma glucose (P < 0.0001). Furthermore, we found a significant association between a variation in fasting plasma glucose and the interaction term comprised of a PON2 codon 148 genetic variation and the presence of noninsulin-dependent diabetes mellitus (NIDDM; P < 0.0001). We then analyzed subjects according to PON2 genotype and NIDDM status. In subjects with NIDDM, the PON2 codon 148 G/G homozygotes had significantly higher mean fasting plasma glucose than subjects with the other two genotypes (P < 0.0001). However, in non-NIDDM subjects, there was no difference in mean fasting plasma glucose among any of the genotypes. There was no association of the PON2 genotype with NIDDM itself, with impaired glucose tolerance, or with other quantitative traits related to NIDDM in this sample. These findings suggest that 1) the PON2 G148 gene variant worsens glycemia in subjects with NIDDM; 2) defining the physiological role of the PON2 gene product would be worthwhile; and 3) genetic factors can modify the severity of clinical phenotypes in subjects with NIDDM.

Adolescent↗
PubMed2004

The gene responsible for PARK6 Parkinson's disease, PINK1, does not influence common forms of parkinsonism.

Mutations in the PINK1 gene (PARK6), a putative serine-threonine kinase, cause autosomal recessive Parkinson's disease. PINK1 functions as a protein kinase and confers protective effects in the mitochondria, where it is primarily located. We assessed in a population of European ancestry whether common genetic variation in this novel gene influences nonmendelian forms of Parkinson's disease. We defined the linkage disequilibrium structure of PINK1 and used this to identify a set of tagging single nucleotide polymorphisms that we estimate will efficiently represent all of the common DNA variation in the entire gene. Genotyping these tags in a set of 576 Parkinson's disease patients and 514 controls did not demonstrate a case-control partition for allele or for haplotype and thus provides evidence against the existence of a common functional variants in PINK1 that has a strong influence on PD risk.

Adult↗
PubMed2002

Sequence variation in the human T-cell receptor loci.

Identifying common sequence variations known as single nucleotide polymorphisms (SNPs) in human populations is one of the current objectives of the human genome project. Nearly 3 million SNPs have been identified. Analysis of the relative allele frequency of these markers in human populations and the genetic associations between these markers, known as linkage disequilibrium, is now underway to generate a high-density genetic map. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system (e.g., asthma, atopy and autoimmunity). Over the past two decades, hundreds of SNPs in the TCR loci have been identified. Most studies have focused on defining SNPs in the variable gene segments which are involved in antigenic recognition. On average, the coding sequence of each TCR variable gene segment contains two SNPs, with many more found in the 5', 3' and intronic sequences of these segments. Therefore, a potentially large repertoire of functional variants exists in these loci. Association between SNPs (linkage disequilibrium) extends approximately 30 kb in the TCR loci, although a few larger regions of disequilibrium have been identified. Therefore, the SNPs found in one variable gene segment may or may not be associated with SNPs in other surrounding variable gene segments. This suggests that meaningful association studies in the TCR loci will require the analysis and typing of large marker sets to fully evaluate the role of TCR loci in common disease susceptibility in human populations.

Chromosome Mapping↗
PubMed1993

Common themes and cultural variations in Japanese and American mothers' speech to infants.

This study explored both universal features and cultural variation in maternal speech. Japanese and American mothers' speech to infants at 6, 12, and 19 months was compared in a cross-sectional study of 60 dyads observed playing with toys at home. Mothers' speech in both cultures shared common characteristics, such as linguistic simplification and frequent repetition, and mothers made similar adjustments in their speech to infants of different ages. American mothers labeled objects more frequently and consistently than did Japanese mothers, while Japanese mothers used objects to engage infants in social routines more often than did American mothers. American infants had larger noun vocabularies than did Japanese infants, according to maternal report. The greater emphasis on object nouns in American mothers' speech is only partially attributable to structural differences between Japanese and English. Cultural differences in interactional style and beliefs about child rearing strongly influence the structure and content of speech to infants.

Adolescent↗
PubMed2006

High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 people.

The insulin-degrading enzyme is responsible for the intracellular proteolysis of insulin. Its gene IDE is located on chromosome 10, in an area with suggestive linkage to type 2 diabetes and related phenotypes. Due to the impact of genetic variants of this gene in rodents and the function of its protein product, it has been proposed as a candidate gene for type 2 diabetes. Various groups have explored the role of the common genetic variation of IDE on insulin resistance and reported associations of various single nucleotide polymorphisms (SNPs) and haplotypes on both type 2 diabetes and glycemic traits. We sought to characterize the haplotype structure of IDE in detail and replicate the association of common variants with type 2 diabetes, fasting insulin, fasting glucose, and insulin resistance. We assessed linkage disequilibrium, selected single-marker and multimarker tags, and genotyped these markers in several case-control and family-based samples totalling 4,206 Caucasian individuals. We observed no statistically significant evidence of association between single-marker or multimarker tests in IDE and type 2 diabetes. Nominally significant differences in quantitative traits are consistent with statistical noise. We conclude that common genetic variation at IDE is unlikely to confer clinically significant risk of type 2 diabetes in Caucasians.

Diabetes Mellitus, Type 2↗
PubMed2005

Stepwise normalization of two-channel spotted microarrays.

Intensities measurements of spotted microarrays embody many undesirable systematic variations. Very commonly, varying amounts and types of such variations are observed in different arrays. Although various normalization methods have been proposed to remove such systematic effects, it has not been well studied how to assess or select the most appropriate method for different arrays and data sets. To address this issue, we present a novel normalization technique, STEPNORM, for data-dependent and adaptive normalization of two-channel spotted microarrays. STEPNORM performs a stepwise interrogation of a range of different normalization models and selects the appropriate method based on formal model selection criteria. In addition, we evaluate the effectiveness of STEPNORM and other commonly used normalization methods utilizing a set of specially constructed splicing arrays.

Journal Article↗
PubMed2004

Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice.

Investigation of sequence variation in common inbred mouse strains has revealed a segmented pattern in which regions of high and low variant density are intermixed. Furthermore, it has been suggested that allelic strain distribution patterns also occur in well defined blocks and consequently could be used to map quantitative trait loci (QTL) in comparisons between inbred strains. We report a detailed analysis of polymorphism distribution in multiple inbred mouse strains over a 4.8-megabase region containing a QTL influencing anxiety. Our analysis indicates that it is only partly true that the genomes of inbred strains exist as a patchwork of segments of sequence identity and difference. We show that the definition of haplotype blocks is not robust and that methods for QTL mapping may fail if they assume a simple block-like structure.

Alleles↗
PubMed1999

Geographical variation of the skull morphology of the common tree shrew (Tupaia glis).

Geographical variation was examined morphologically in the common tree shrew (Tupaia glis) in some Indochinese and Malayan regions. Osteometrical examination and principal component analysis elucidated the morphological differences among various populations. The populations from southern and western Thailand were distinguished morphologically from the other populations. Variation in males from south Thailand and Kuala Lumpur suggests that the Isthmus of Kra may have an influence on the variation of skull morphology. However, the Isthmus of Kra was not completely considered as a factor of geographical separation in this species, because we could not confirm the separation in skull size and shape between the localities at least in females. While, the Kanchanaburi population in western Thailand was significantly smaller than the other population in skull size, and constituted the morphologically separable group in our study.

Animals↗
PubMed2001

Oncogene lineages of human papillomavirus type 16 E6, E7 and E5 in preinvasive and invasive cervical squamous cell carcinoma.

Human papillomavirus (HPV)16 accounts for about 60% of the HPV infections in invasive cervical cancer (ICC). There are many sequence variations within HPV16, some of which have been associated with different biological properties, although no definite correlations have yet been established. However, the definition 'variant' has been a source of confusion in research and diagnosis, since it is based on all sequence deviations from a randomly selected prototype. This study has sequenced the HPV16 oncogenes E6, E7 and E5 from 61 Swedish cases with cervical intraepithelial neoplasia grade III (CIN III) or ICC. Clustering the sequence variations at the three common sites of variation (nucleotide 350 in E6, which has previously been associated with the progression from CIN III to ICC, and nucleotides 3979 and 4042 in E5) resulted in the distinction of three major oncogene lineages encompassing more than 95% of the cases, and two minor oncogene lineages. Simple comparison of the distribution of the individual variations or oncogene lineages between CIN III and ICC showed no significant difference, but the number of variations in addition to the three common ones was significantly higher in ICC. This novel classification scheme, based on the variations in the E6, E7 and E5 region, is considered to be a major improvement over the classical 'prototype-variant' classification, and can help to clarify the interpretation of HPV sequence data in relation to the progression of cervical cancer.

Carcinoma, Squamous Cell↗
PubMed2006

Genetic profiling as a marker for risk of sudden cardiac death.

PURPOSE OF REVIEW: Clinical trials provide evidence that an empirical approach of implantable cardioverter-defibrillator implantation in all heart failure patients (ejection fraction </= 35%) with mild to moderate symptoms effectively reduces mortality rate as compared to the best available medical therapy. At least 50% of patients, however, will succumb to a non-arrhythmic demise and over half of all patients will not require device therapy over long-term follow-up. Thus, the approach of empiric implantable cardioverter-defibrillator implantation is costly in light of the considerable expense of device cost, implantation, and patient follow-up. This review discusses the prospect of genomic medicine as an approach to assess genetic susceptibility to sudden arrhythmic death in at-risk populations. RECENT FINDINGS: Through the past 10 years of primary prevention implantable cardioverter-defibrillator trials, the number of patients needed to treat to prevent a sudden death has risen from one in four patients to one in 14. Although numerous clinical tests exist for stratification, they are of low positive predictive value in assessing arrhythmic risk, and have not been prospectively validated as effective strategies in identifying arrhythmia-prone patients. Recent data from genetic studies identifying genes responsible for sudden cardiac death have compiled a list of relatively common genetic variations (polymorphisms). These polymorphisms, encoding for proteins known to be involved in cardiac electrophysiology, may contribute to arrhythmic risk in the milieu of heart failure. SUMMARY: Current clinical indications for implantable cardioverter-defibrillator implantation in primary prophylaxis of sudden cardiac death necessarily include a significant number of patients who may not benefit. The identification of common genetic variations causing an increased risk of vulnerability to ventricular arrhythmia in heart failure patients may optimize the use of medical resources through rapid identification of sub-populations at highest risk.

Arrhythmias, Cardiac↗
PubMed1995

Morphology of the retromandibular vein in relation to the facial nerve in the parotid gland.

In order to help avoid complications of parotid surgery, we investigated the relationship between the facial nerve and the retromandibular vein. Fifty dissections were performed on 30 cadavers. In 45 (90%) of the cases the retromandibular vein was located on the medial side of the upper and lower trunks of the facial nerve, and in 5 (10%), the course of the retromandibular vein was lateral to the lower trunks and medial to the upper trunks. These variations were divided into subgroups. The most commonly encountered variation was that the retromandibular vein crossed the facial nerve from the medial (34 cases) or lateral side (3 cases) at a point between the bifurcation and ramification points of the lower facial trunk. In one case, the retromandibular vein was detected on the lateral side of the facial nerve at the bifurcation. In 3 cases (15%), the course of the retromandibular vein was different on the right and left sides of the face in the same cadaver.

Adult↗
PubMed1975

Electrophoretic study of human ribosomal core proteins: evidence for selection against variation.

Ten human ribosomal core proteins examined electrophoretically showed significantly less polymorphic variation than expected on the basis of other protein systems studied. This implies that selective forces may restrict variation at these loci. Variation in common multigenic traits must be determined by a combination of common alleles. If there is restriction of variation at certain types of loci, a limit is placed on the number of loci which can play a role in multigenic inheritance. Surveys for polymorphism in groups of proteins with similar structural or functional roles will further define these limits.

Female↗
PubMed2004

Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology.

The chromogranin/secretogranin proteins are costored and coreleased with catecholamines from secretory vesicles in chromaffin cells and noradrenergic neurons. Chromogranin A (CHGA) regulates catecholamine storage and release through intracellular (vesiculogenic) and extracellular (catecholamine release-inhibitory) mechanisms. CHGA is a candidate gene for autonomic dysfunction syndromes, including intermediate phenotypes that contribute to human hypertension. Here, we show a surprising pattern of CHGA variants that alter the expression and function of this gene, both in vivo and in vitro. Functional variants include both common alleles that quantitatively alter gene expression and rare alleles that qualitatively change the encoded product to alter the signaling potency of CHGA-derived catecholamine release-inhibitory catestatin peptides.

Amino Acid Sequence↗
PubMed2000

Apolipoprotein E4: an allele associated with many diseases.

Apolipoprotein E (apoE) was discovered as a plasma protein involved in lipoprotein metabolism. ApoE is synthesized by the liver and is also made locally in the brain. There are three common variants of apoE, resulting from common genetic variation, called E2, E3 and E4. The E3 allele is the most prevalent form, and the proportion of the three alleles differs between populations. Epidemiological studies have found that the E4 allele is associated with decreased longevity, increased plasma cholesterol levels and increased prevalence for cardiovascular disease and particularly for Alzheimer's disease. The apoE polymorphism also affects response to head trauma, cognitive decline upon ageing and several other disorders. Thus, common genetic variation in the apoE gene may be associated with successful ageing.

Aging↗
PubMed2004

Radiological study of the intumescentia septi nasi anterior.

Intumescentia septi nasi anterior (ISNA) is a common anatomical variation that is not routinely noticed by surgeons or radiologists. ISNA is a mucosal bulging located on each side of the anterior part of the septum. The aim of this study was to investigate the prevalence of ISNA in different ages and sexes. In this study, computerized tomography (CT) scans of the paranasal sinus were obtained from 595 patients who had symptoms of chronic sinusitis. Among 595 subjects, ISNA was found in 332 (55.79 per cent) of subjects. It was found more frequently in males than females in every age group. Although ISNA is a common anatomical variation, it is generally overlooked. This is the first report on ISNA in different age groups and sexes.

Adolescent↗
PubMed1999

Genetics of osteoporosis.

There is clear evidence of genetic modulation of bone phenotype parameters including bone density, quantitative ultrasound, bone size, and bone turnover. At any particular age and phase of life, genetic factors explain about 70% of the variance in bone phenotype after adjustment for major medical and disease factors. Hormonal factors, diet, and lifestyle interact with those genetic factors over time. Common allelic variation in the VDR was the first of several genes and now chromosomal loci to be implicated in the genetic determination of bone phenotype. The VDR polymorphisms have an effect weaker than originally reported, and part of the allelic effects may be mediated by effects on body size and development and even other hormonal regulators such as PTH or insulin. Irrespective of the strength or mechanism of these associations, these initial findings on the VDR stimulated the field of the genetics of osteoporosis with targeted genetic studies and now genome scan approaches. Intronic polymorphisms of the collagen I alpha 1 gene have been shown to be related to bone density and to fracture risk in several studies, although not all findings concur. Common allelic variations have now been associated with bone density for the estrogen receptor, TGF beta receptor, and TGF beta 1, for the insulin-like growth factor-I pathway, for interleukin-4 and -6 and the interleukin-1 receptor antagonist, for calcitonin and the PTH receptors and for apolipoprotein E. Of considerable interest, chromosomal loci, notably 11q 12-13, have now been linked to bone phenotypes in human and mouse studies. The mouse strain studies seem likely to be powerful tools providing insight to important human loci based on the mouse-human chromosomal synteny. Variability of genetic findings across studies seems to be the rule rather than the exception. This variability may relate to interaction of particular loci with specific environmental or even other genetic loci. The importance of genetic heterogeneity, including ethnicity, as well as environmental and hormonal confounders, such as calcium and vitamin D intake, hormonal status and skeletal and body size, will need to be taken into account in future gene search approaches. Genome scans in relation to bone density and fracture end-points will need to account for such important potential confounders in each target population. Interactions between genetic and environmental factors, including lifestyle, have been investigated initially for the VDR polymorphisms in relation to the response of bone density and turnover to calcium intake and treatment with simple vitamin D and active vitamin D compounds. Gene-gene and gene-environment interactions in human and animal models will be critical targets for future research. Further genes with positive and negative effects on bone phenotype are certain to be identified in the near future. Each of these will need to be evaluated in relation to potential environmental modulators in pharmacogenetic models. Understanding the molecular physiology of such gene effects is likely to lead to more specific treatments and to allow the selection of more appropriate and effective treatment options.

Animals↗
PubMed2006

Genetic variation in leaf pigment, optical and photosynthetic function among diverse phenotypes of Metrosideros polymorpha grown in a common garden.

Coordinated variation has been reported for leaf structure, composition and function, across and within species, and theoretically should occur across populations of a species that span an extensive environmental range. We focused on Hawaiian keystone tree species Metrosideros polymorpha, specifically, 13-year old trees grown (2-4 m tall) in a common garden (approximately 1 ha field with 2-3 m between trees) from seeds collected from 14 populations along an altitude-soil age gradient. We determined the genetic component of relationships among specific leaf area (SLA), the concentrations of nitrogen (N) and pigments (chlorophylls, carotenoids, and anthocyanins), and photosynthetic light-use efficiency. These traits showed strong ecotypic variation; SLA declined 35% with increasing source elevation, and area-based concentrations of N, Chl a + b and Car increased by 50, 109 and 96%, respectively. Concentrations expressed on a mass basis were not well related to source elevation. Pigment ratios expressed covariation that suggested an increased capacity for light harvesting at higher source elevation; Chl/N and Car/Chl increased with source elevation, whereas Chl a/b declined; Chl a/b was higher for populations on younger soil, suggesting optimization for low N supply. Parallel trends were found for the photosynthetic reactions; light-saturated quantum yield of photosystem II (Phi (PSII)) and electron transport rate (ETR) increased with source elevation. Correlations of the concentrations of photosynthetic pigments, pigment ratios, and photosynthetic function across the ecotypes indicated a stoichiometric coordination of the components of the light-harvesting antennae and reaction centers. The constellation of coordinated morphological, biochemical and physiological properties was expressed in the leaf reflectance and transmittance properties in the visible and near-infrared wavelength region (400-950 nm), providing an integrated metric of leaf status among and between plant phenotypes.

Altitude↗
PubMed1998

Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. We have tested the insulin gene (INS) variable number of tandem repeats (VNTR) locus, which in Caucasians has two main allele sizes (class I and class III; ref. 3), as a functional candidate polymorphism for association with size at birth, as it has been shown to influence transcription of INS (refs 3-5). In a cohort of 758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birth: class III homozygotes had larger mean head circumference (P=0.004) than class I homozygotes. These associations were amplified in babies who did not show postnatal realignment of growth (45%), and were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS VNTR III/II genotype might have bestowed a perinatal survival during human history by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.

Birth Weight↗