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PubMed2006

Genetic and cultural transmission of smoking initiation: an extended twin kinship model.

BACKGROUND: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a significant role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. METHODS: We examined the role of genetic and environmental factors for smoking initiation using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission. A dichotomous lifetime smoking measure was obtained from twins and relatives in the Virginia 30,000 sample. RESULTS: Results demonstrate that both genetic and environmental factors play a significant role in the liability to smoking initiation. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission and resulting genotype-environment covariance. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (i) age x gene interaction, and (ii) social homogamy. Neither mechanism provided a significantly better explanation of the data, although age regression was significant. CONCLUSIONS: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on smoking initiation.

Aged↗

PubMed2004

Identification and comparative analysis of components from the signal recognition particle in protozoa and fungi.

BACKGROUND: The signal recognition particle (SRP) is a ribonucleoprotein complex responsible for targeting proteins to the ER membrane. The SRP of metazoans is well characterized and composed of an RNA molecule and six polypeptides. The particle is organized into the S and Alu domains. The Alu domain has a translational arrest function and consists of the SRP9 and SRP14 proteins bound to the terminal regions of the SRP RNA. So far, our understanding of the SRP and its evolution in lower eukaryotes such as protozoa and yeasts has been limited. However, genome sequences of such organisms have recently become available, and we have now analyzed this information with respect to genes encoding SRP components. RESULTS: A number of SRP RNA and SRP protein genes were identified by an analysis of genomes of protozoa and fungi. The sequences and secondary structures of the Alu portion of the RNA were found to be highly variable. Furthermore, proteins SRP9/14 appeared to be absent in certain species. Comparative analysis of the SRP RNAs from different Saccharomyces species resulted in models which contain features shared between all SRP RNAs, but also a new secondary structure element in SRP RNA helix 5. Protein SRP21, previously thought to be present only in Saccharomyces, was shown to be a constituent of additional fungal genomes. Furthermore, SRP21 was found to be related to metazoan and plant SRP9, suggesting that the two proteins are functionally related. CONCLUSIONS: Analysis of a number of not previously annotated SRP components show that the SRP Alu domain is subject to a more rapid evolution than the other parts of the molecule. For instance, the RNA portion is highly variable and the protein SRP9 seems to have evolved into the SRP21 protein in fungi. In addition, we identified a secondary structure element in the Saccharomyces RNA that has been inserted close to the Alu region. Together, these results provide important clues as to the structure, function and evolution of SRP.

Amino Acid Sequence↗

PubMed1997

A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease.

We studied the outcome of 436 patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) who underwent orthotopic liver transplant (OLT) at three major liver transplant centers. Univariate predictors of outcome included age, Karnofsky score, Child's class, Mayo risk score, United Network for Organ Sharing (UNOS) status, nutritional status, serum albumin, serum bilirubin, international normalized ratio, and the presence of ascites, encephalopathy, renal failure (serum creatinine > 2 mg/dL), and edema refractory to diuretics. Using these predictors, we developed a four variable mathematical prognostic model to help the liver transplant physician predict the following: 1) the amount of intraoperative blood loss; 2) the number of days in the intensive care unit (ICU); and 3) severe complications after surgery. The model uses age, renal failure, Child's class, and United Network for Organ Sharing status. This study is the first to model the outcome of liver transplant in patients with a specific etiology of chronic liver disease (PBC or PSC). The model may be used to help select patients for OLT and to plan the timing of their transplantation.

Analysis of Variance↗

PubMed1995

Genetic variation of wild Puumala viruses within the serotype, local rodent populations and individual animal.

Reverse transcriptase polymerase chain reaction cloning and sequencing were used to determine the range of S gene/N protein variability in wild Puumala virus (PUU) strains and to study phylogenetic relationships between two groups of strains which originated from Finland and from European Russia. Analyses of the nucleotide and predicted amino acid sequences showed: (1) all PUU strains shared a common ancient ancestor; and (2) the more recent ancestors were different for the Finnish branch and the Russian branch of PUU strains. A cluster of amino acid substitutions in the N protein of Finnish strains was found; this cluster was located within a highly variable region of the molecule carrying B-cell epitopes (Vapalahti et al., J. Med. Virol., 1995, in press). Different levels of S gene/N protein diversity of PUU were revealed supporting the view of geographical clustering of genetic variants. Puumala virus from individual voles was found to be a complex mixture of closely related variants-quasispecies. The ratio of non-silent to silent nucleotide mutations registered in the S genes/N proteins of PUU quasispecies was 4- to 16-fold higher than that in Puumala virus strains, resulting in a more wide range of quasispecies N protein sequence diversity.

Amino Acid Sequence↗

PubMed1995

Hepatitis B sero-prevalence and risk factors among school-age children in a low socioeconomic community, Bangkok.

A cross-sectional study of 165 school-age children who had no history of HBV vaccination was carried out in a low socioeconomic community of Din-Daeng, Bangkok. Blood specimens were collected for determination of HBV seromarkers (HBsAg, Anti-HBs and Anti-HBc) by EIA commercial kits. The results showed that the prevalence of HBV seromarkers was 24.85%, the HBsAg carrier rate was 3.64%, the anti-HBs positive rate was 15.15%, and the prevalence of only anti-HBc was 6.06%. To investigate factors associated with the positivity of HBV seromarkers, children were divided into two groups--the first group consisted of 41 children with HBV seromarkers and the second consisted of 124 children without HBV seromarkers. The study variables between the two groups were compared and analysed. The results revealed that factors associated with HBV positivity were (a) child factors: child's age, child's sex, ear piercing in female, sharing blade during haircutting, contact wound from other persons, using wares with other persons, searching things in garbage, and (b) family factors: older parent, low education in parent, low family income per month, low parent's knowledge and attitude about HBV infection and vaccination, (P < 0.05). After using stepwise regression analysis, the factor of ear piercing in female was only one significant variable.

Adolescent↗

PubMed1991

Histologic classification of the combined nevus. Analysis of the variable expression of melanocytic nevi.

The designation combined nevus gives recognition to mixed cytologic patterns. In the common variant, plump, pigmented spindle cells form fascicles among nests of ordinary nevus cells. In other variants, one or several cellular components that share cytologic features with either a blue nevus or a Spitz nevus are represented. Ninety-five cases, 49% of which were of the common type, were studied. Grossly, most of the lesions were darkly pigmented papules or nodules. The clinical diagnosis in three-fourths of the cases was nevus, blue nevus, or melanoma. Fifteen percent had concomitant histologic features of melanocytic dysplasia, and most of these lesions were of the common type. For the common variant, the cytologic features, pattern of apparent infiltration, and variable representation of the features of a premalignant melanocytic dysplasia often mislead a pathologist in interpreting and predicting biologic potential. In combined nevi, the phenotypic diversity and genetic lability of melanocytic nevus cells is manifested.

Adolescent↗

PubMed2001

A reevaluation of the common factor theory of shared variance among age, sensory function, and cognitive function in older adults.

The common cause hypothesis of the relationship among age, sensory measures, and cognitive measures in very old adults was reevaluated. Both sensory function and processing speed were evaluated as mediators of the relationship between age and cognitive function. Cognitive function was a latent variable that comprised 3 factors including memory, speed, and verbal ability. The sample was population based and comprised very old adults (n = 894; mean age = 77.7, SD = 5.6 years) from the Australian Longitudinal Study of Ageing. The results showed that there was common variance in the cognitive factor shared by age, speed, vision, and hearing but that specific effects of age on cognition remained. Furthermore, speed did not fully mediate the effect of age or sensory function on cognition. Some age differences in cognitive performance are not explained by the same processes that explain age differences in sensory function and processing speed.

Aged↗

PubMed1994

Life events and stress reactivity as predictors of cancer, coronary heart disease and anxiety disorders.

The topic relative to the differential psychobiological mechanisms between cancer and coronary illness has been showing for the last years. In this sense, some theoretical models which have been formulated by relevant authors have suggested the possibility of differentiating cancer and cardiovascular disease, both the onset and the progression, from coping strategies, personality variables and affective states, as well as the different categories of psychosocial stress. Likewise, the implication of psychological distress, such as anxiety, anger and depression for the occurrence of somatic disease has been reported frequently. This research was designed to analyze the psychosocial patterns which could explain the incidence of heart disease, cancer and anxiety based disorders. Measures of life events and stress reactivity were obtained from a total of 109 patients diagnosed as having breast cancer (37), infarct (37), and anxiety (35), and from 72 normal control subjects. Our data tend to show that the cancer group was strongly predicted by lost and illness events, while the coronary group was more associated with work events. The anxiety disorders group lacked a life events dimension, but shared the same category of the infarct group. We also found a strong relationship between depressive reactions and cancer in contrast to the anxiety-anger variable that was more relevant in the infarct patients. The interaction between internal and external stress factors in the etiology of disease is also discussed.

Adjustment Disorders↗

PubMed1983

Similarities between transplantation antigens on methylcholanthrene-induced sarcomas and T-cell regulatory molecules.

Successful interaction among T-cell subsets requires, among other things, homology at certain genetic loci that code for cellular interaction molecules (CIM). One such interaction, the induction of an acceptor-cell population by an Ly-1 T-suppressor-inducer cell, is controlled by genes that map to the variable region of the immunoglobulin heavy chain (Igh) complex. If the suppressor-induced cells (or their cell-free products) do not share Igh-V polymorphisms with their acceptor cells, the induction event fails to take place. Recently, structural genes of a transplantation antigen on the methylcholanthrene-induced sarcoma Meth A were mapped to the same region of chromosome 12 as the Igh gene complex. We tested whether there was any relationship between the Meth A transplantation antigen and T-cell regulatory molecules by using antisera against the Meth A antigen to block this particular Igh-linked T-T interaction. We found that isoantisera against a large number of methylcholanthrene-induced sarcomas tested were capable of blocking the induction of T-suppressor cells so long as the inducer and acceptor cells bore the Igha polymorphism. Further, we found a structural gene on MC-induced tumors that could absorb out this activity, and the structural gene for this antigen is coded for the same region as the Igh gene loci. The antisera binds to the I-J+ portion of a T-cell regulatory molecule Ly-1 TsiF, the portion of the molecule that has no specificity for antigen and imparts the Igh-linked genetic restriction. The implications of these findings for both oncology and immunology were discussed.

Animals↗

PubMed2004

On the challenges of using evidence-based information: the role of clinical uncertainty.

Evidence-based medicine helps physicians appraise the latest and best evidence and incorporate patient's values in reaching a shared clinical decision. However, many decisions in medicine are made in the paucity of best evidence. Medical uncertainty remains inherent in clinical practice and contributes to significant variability in the way physicians and patients manage medical problems. Physicians and patients have varying degrees of tolerance for uncertainty. Intolerance to uncertainty among physicians results in increased test ordering tendencies, variability in medical treatment, failure to comply with evidence-based guidelines, and even guide career choices. Factors that result in the variability of physicians' interpretation of an effective treatment include: patient factors (prioritizing some factors over others), physician factors (lack of knowledge, lack of resources, medical uncertainty), and environmental factors (limitation of time and practice). Several approaches that have been found useful in implementing evidence in clinical practice include: sending reminders to prompt physicians to perform patient-related clinical activities, introducing computer information systems to support practice, and using interactive education interventions to teach newer skills and challenge negative attitudes. Passive educational approaches, like dissemination of guidelines and didactic lectures, are usually less useful in changing behavior. Among the techniques found to be useful for managing uncertainty are shared decision making, meticulous history taking, and physical examination, excluding worrisome differential diagnosis and establishing trust in patients. The role of future studies in assessing the outcome of multiple evidence-based strategies in situations of medical uncertainty remains to be explored.

Evidence-Based Medicine↗

PubMed1989

And then there was snow in Alaska: a sharing of experience with Allan Wicker.

A perennial problem with theorizing is the improper context which experiments and correlational studies assume without understanding first the environmental levels of correspondence at which variables operate in nature. Ecological studies show variables can operate within separate contexts in such a way as to cancel the influence if too large or too small a context is chosen. One must first determine the proper level of correspondence before investigating the causal relationship. An example of the variable of snow in Alaska is explored and different levels of correspondence cited in attitude studies and economics. Only when levels of correspondence are understood does the true causal relationship permit measurement and interpretation.

Alaska↗

PubMed2005

tax and rex Sequences of bovine leukaemia virus from globally diverse isolates: rex amino acid sequence more variable than tax.

Bovine leukaemia virus (BLV) is an important agricultural problem with high costs to the dairy industry. Here, we examine the variation of the tax and rex genes of BLV. The tax and rex genes share 420 bases and have overlapping reading frames. The tax gene encodes a protein that functions as a transactivator of the BLV promoter, is required for viral replication, acts on cellular promoters, and is responsible for oncogenesis. The rex facilitates the export of viral mRNAs from the nucleus and regulates transcription. We have sequenced five new isolates of the tax/rex gene. We examined the five new and three previously published tax/rex DNA and predicted amino acid sequences of BLV isolates from cattle in representative regions worldwide. The highest variation among nucleic acid sequences for tax and rex was 7% and 5%, respectively; among predicted amino acid sequences for Tax and Rex, 9% and 11%, respectively. Significantly more nucleotide changes resulted in predicted amino acid changes in the rex gene than in the tax gene (P < or = 0.0006). This variability is higher than previously reported for any region of the viral genome. This research may also have implications for the development of Tax-based vaccines.

Amino Acid Sequence↗

PubMed1998

Screening for variability in the ciliary neurotrophic factor (CNTF) gene: no evidence for association with human obesity.

Systemic administration of the neurocytokine ciliary neurotrophic factor (CNTF) normalizes the obese phenotype of ob/ob and db/db mice. CNTF exerts its multiple effects through a receptor complex whose sequence, localization in hypothalamic nuclei and mode of signal transduction share remarkable similarities with the leptin receptor. In the human CNTF gene, a mutation in the first intron creates a new splice acceptor site, with the resulting mRNA coding for an aberrant protein (Takahashi et al., 1994). Given the potential of CNTF to influence energy homeostasis, this study was undertaken to determine whether variability in the CNTF gene is associated with human obesity. The previously described mutation was found in 30.3% of obese children and adolescents, 7 of which were homozygous (allele frequency 0.163). 29.5% of lean subjects carried the mutation, none of which were homozygous (allele frequency 0.148; corrected p = 1 compared to obese). No further mutations were detected by single strand conformational polymorphism (SSCP) analysis. In conclusion, variants in the CNTF gene are unlikely to be associated with the development of early-onset obesity.

Adolescent↗

PubMedDate not supplied

Molecular genetic and morphological analyses of the African wild dog (Lycaon pictus).

African wild dog populations have declined precipitously during the last 100 years in eastern Africa. The possible causes of this decline include a reduction in prey abundance and habitat; disease; and loss of genetic variability accompanied by inbreeding depression. We examined the levels of genetic variability and distinctiveness among populations of African wild dogs using mitochondrial DNA (mtDNA) restriction site and sequence analyses and multivariate analysis of cranial and dental measurements. Our results indicate that the genetic variability of eastern African wild dog populations is comparable to that of southern Africa and similar to levels of variability found in other large canids. Southern and eastern populations of wild dogs show about 1% divergence in mtDNA sequence and form two monophyletic assemblages containing three mtDNA genotypes each. No genotypes are shared between the two regions. With one exception, all wild dogs examined from zoos had southern African genotypes. Morphological analysis supports the distinction of eastern and southern African wild dog populations, and we suggest they should be considered separate subspecies. An eastern African wild dog breeding program should be initiated to ensure preservation of the eastern African form and to slow the loss of genetic variability that, while not yet apparent, will inevitably occur if wild populations continue to decline. Finally, we examined the phylogenetic relationships of wild dogs to other wolf-like canids through analysis of 736 base pairs (bp) of cytochrome b sequence and showed wild dogs to belong to a phylogenetically distinct lineage of the wolf-like canids.

Africa, Eastern↗

PubMed1997

Micro- and macrogeographical genetic structure of colonies of naked mole-rats Heterocephalus glaber.

Patterns of genetic structure in eusocial naked mole-rat populations were quantified within and among geographically distant populations using multilocus DNA fingerprinting and mitochondrial DNA (mtDNA) sequence analysis. Individuals within colonies were genetically almost monomorphic, sharing the same mtDNA control region haplotype and having coefficients of band sharing estimated from DNA fingerprints ranging from 0.93 to 0.99. Family analysis of a hybrid captive colony of naked mole-rats with increased levels of genetic variability using multilocus DNA fingerprinting gave results consistent with Mendelian inheritance, and has revealed for the first time that multiple paternity can occur. In a survey of wild colonies from Ethiopia, Somalia and locations in northern and southern Kenya, we have examined mtDNA control region sequence variation in 42 individuals from 15 colonies, and together with multilocus DNA fingerprinting and mtDNA cytochrome-b sequence analysis in selected individuals have shown that these populations show considerable genetic divergence. Most of the variance in sequence divergence was found to be between geographical locations (phi ct = 0.68) and there was a significant correlation between sequence divergence and geographical separation of haplotypes. Six colonies from Mtito Andei in southern Kenya shared the same control region haplotype, suggesting a recent common maternal ancestor. In contrast, out of four colonies at Lerata in north Kenya, three haplotypes were identified, and phylogenetic analysis suggests that this area may be a zone where two distinct lineages are in close proximity. Genetic distances were maximal between Ethiopian and southern Kenyan populations at 5.8% for cytochrome-b, and are approaching interspecific values seen between other Bathyergids.

Animals↗

PubMed1998

Social cognitive predictors of nutritional risk in rural elderly adults.

According to Social Cognitive Theory (Bandura, 1997), nutritional risk would be predicted by perceptions of nutrition efficacy, which in turn would be predicted from four sources: modeling, verbal support, physiological conditions, and nutrition habits. In telephone interviews with 154 rural elderly adults (44 men, 110 women; mean age = 74.4 years), nutritional risk was measured with Nutritional Risk Index (NRI), Nutritional Screening Initiative (NSI), and seven-high-risk-nutrients consumed less than 50 percent of RDA (Diet Plus Analysis). Nutrition-efficacy was measured with a new twenty-five-item scale of Perceived Nutrition Barriers (PNB). Sources of nutrition-efficacy included: mealtime modeling--shared meals, household size; verbal support--people talk to each day, hours talked, number of confidants; physiological conditions that may affect nutrition--age, body mass, medications, disability, negative affect, and nutrition habits--daily food variety, use of meal services. Path analysis was performed with each measure of nutritional risk (NRI, NSI, 7-high-risk-nutrients) as a criterion variable, nutrition-efficacy (PNB) as a possible mediating variable, and sources of nutrition-efficacy as predictor variables. Social Cognitive variables accounted for 58 percent of variance in NRI, 49 percent of variance in NSI, and 29 percent of variance in seven-high-risk-nutrients. Nutritional risk was directly predicted by large households, few shared meals, few confidants, high body mass, many medications, and few daily foods; it was indirectly predicted (via PNB) by high levels of negative affect. Perceived Nutrition Barriers (PNB) most often mentioned were food cost, eating alone, food tastelessness, transportation to the store, and chewing difficulty.

Aged↗

PubMed2002

Genetic association mapping at the crossroads: which test and why? Overview and practical guidelines.

Until about a decade ago, genetic association testing essentially meant case control association analysis using genetic markers. Concerns about population stratification propelled family-based tests of association into widespread use and challenged the classic case control design. The literature now contains a vast collection of different family-based methods, most of which are based on the transmission/disequilibrium test (TDT). Some methods extend the original TDT to accommodate multiallelic markers, variable pedigree constellations, multiple loci, etc. Other methods go beyond the original design of the TDT to detect genetic association via haplotype sharing. Most recently, we have witnessed a revival of case control methods that control for population stratification. The purpose of this review is to help orient readers to the rapidly developing methods of association testing and enhance their understanding of the basic principles of these approaches. We present an overview of the development of genetic association tests, with practical guidelines on which test might be the most suitable for a given study.

Case-Control Studies↗

PubMed2004

Isolation, characterization, and recombinant expression of multiple serpins from the cat flea, Ctenocephalides felis.

Several clones encoding serine protease inhibitors were isolated from larval and adult flea cDNA expression libraries by immunoscreening and PCR amplification. Each cDNA contained an open reading frame encoding a protein of approximately 45 kDa, which had significant sequence similarity with the serpin family of serine protease inhibitors. The thirteen cDNA clones isolated to date encode serpin proteins, which share a primary structure that includes a nearly identical constant region of about 360 amino acids, followed by a C-terminal variable region of about 40-60 amino acids. The variable C-terminal sequences encode most of the reactive site loop (RSL) and are generated by mutually exclusive alternative exon splicing, which may confer unique protease selectivity to each serpin. Utilization of an alternative exon splicing mechanism has been verified by sequence analysis of a flea serpin genomic clone and adjacent genomic sequences. RNA expression patterns of the cloned genes have been examined by Northern blot analysis using variable region-specific probes. Several putative serpins have been overexpressed using the cDNA clones in Escherichia coli and baculovirus expression systems. Two purified baculovirus-expressed recombinant proteins have N-terminal amino acid sequences identical to the respective purified native mature flea serpins indicating that appropriate N-terminal processing occurred in the virus-infected insect cells.

Animals↗