Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms

The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoletic development and phenotypic variation. BioEssays 25:930-939,2003. (C) 2003 Wiley Periodicals, Inc.

Intra-specific variation for host plant use in Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae): Implications for management

The polyphagous moth Helicoverpa armigera (Hubner) is one of the world's most important agricultural pests. A number of existing approaches and future designs for management of H. armigera rely on the assumption that moths do not exhibit either genetically and/or non-genetically based variation for host plant utilization. We review recent empirical evidence demonstrating that both these forms of variation influence host plant use in this moth. The significance of this variation in H. armigera in relation to current and future pest management strategies is examined. We provide recommendations on future research needs and directions for sustainable management of H. armigera, under a framework that includes consideration of intra.-specific variation for host use relevant in this and other similar pest species. (C) 2004 Elsevier Ltd. All rights reserved.

Multivariate QTL linkage analysis suggests a QTL for platelet count on chromosome 19q

Platelet count is a highly heritable trait with genetic factors responsible for around 80% of the phenotypic variance. We measured platelet count longitudinally in 327 monozygotic and 418 dizygotic twin pairs at 12, 14 and 16 years of age. We also performed a genome-wide linkage scan of these twins and their families in an attempt to localize QTLs that influenced variation in platelet concentrations. Suggestive linkage was observed on chromosome 19q13.13-19q13.31 at 12 (LOD=2.12, P=0.0009), 14 (LOD=2.23, P=0.0007) and 16 (LOD=1.01, P=0.016) years of age and multivariate analysis of counts at all three ages increased the LOD to 2.59 (P=0.0003). A possible candidate in this region is the gene for glycoprotein VI, a receptor involved in platelet aggregation. Smaller linkage peaks were also seen at 2p, 5p, 5q, 10p and 15q. There was little evidence for linkage to the chromosomal regions containing the genes for thrombopoietin (3q27) and the thrombopoietin receptor (1q34), suggesting that polymorphisms in these genes do not contribute substantially to variation in platelet count between healthy individuals.

Effects of dopamine receptor D4 variation on alcohol and tobacco use and on novelty seeking: Multivariate linkage and association analysis

The dopamine D4 receptor gene contains a polymorphic sequence consisting of a variable number of 48-base-pair (bp) repeats, and there have been a number of reports that this polymorphism is associated with variation in novelty seeking or in substance abuse and addictive behaviors. In this study we have assessed the linkage and association of DRD4 genotype with novelty seeking, alcohol use, and smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited from the Australian Twin Registry (ATR). We found no evidence of linkage or association of the DRD4 locus with any of the phenotypes. We made use of repeated measures for some phenotypes to increase power by multivariate genetic analysis, but allelic effects were still non-significant. Specifically, it has been suggested that the DRD4 7-repeat allele is associated with increased novelty seeking in males but we found no evidence for this, despite considerable power to do so. We conclude that DRD4 variation does not have an effect on use of alcohol and the problems that arise from it, on smoking, or on novelty seeking behavior. (C) 2003 Wiley-Liss, Inc.

Major quantitative trait locus for eosinophil count is located on chromosome 2q

Background: Eosinophils are granulocytic white blood cells implicated in asthma and atopic disease. The degree of eosinophilia in the blood of patients with asthma correlates with the severity of asthmatic symptoms. Quantitative trait loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy of mapping genes involved in asthma than linkage analysis using affected relative pairs. 1 Objective: To identify QTLs responsible for variation in eosinophil count in adolescent twins. Methods: We measured eosinophil count longitudinally in 738 pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 centimorgans across the genome. We then used multipoint variance components linkage analysis to test for linkage between marker loci and eosinophil concentrations at each age across the genome. Results: We found highly significant linkage on chromosome 2q33 in 12-year-old twins (logarithm of the odds = 4.6; P = .000002) and suggestive evidence of linkage in the same region in 14-year-olds (logarithm of the odds = 1.0; P = .016). We also found suggestive evidence of linkage at other areas of the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and 22. Conclusion: A QTL for eosinophil count is present on chromosome 2q33. This QTL might represent a gene involved in asthma pathophysiology.

Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia

Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia - and, more recently, for bipolar disorder - on chromosome 6q13-q26. We genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the MOXD1-STX7-TRARs gene cluster at 6q23.2, which contains a number of prime candidate genes for schizophrenia. Thirty-one screening single-nucleotide polymorphisms (SNPs) were selected, providing a minimum coverage of at least 1 SNP/20 kb. The association observed with rs4305745 (P = .0014) within the TRAR4 (trace amine receptor 4) gene remained significant after correction for multiple testing. Evidence for association was proportionally stronger in the smaller AA sample. We performed database searches and sequenced genomic DNA in a 30-proband subsample to obtain a high-density map of 23 SNPs spanning 21.6 kb of this gene. Single-SNP analyses and also haplotype analyses revealed that rs4305745 and/or two other polymorphisms in perfect linkage disequilibrium (LD) with rs4305745 appear to be the most likely variants underlying the association of the TRAR4 region with schizophrenia. Comparative genomic analyses further revealed that rs4305745 and/or the associated polymorphisms in complete LD with rs4305745 could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirm that TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that TRAR4 is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.

Geographic variation in vocalisations of Satin Bowerbirds, Ptilonorynchus violaceus, in south-eastern Queensland

Geographic variation in the advertisement call of the male Satin Bowerbird, Ptilonorhynchus violaceus, was investigated in three populations in south-eastern Queensland. The call was found to differ significantly among the three geographically distinct populations. A discriminant function analysis using five measurements of call frequency and duration provided 100% classification success of the 25 individuals. The observed geographic variation in this call may result from adaptation to the local acoustic environment in these populations, or from genetic or cultural divergence among populations. Further research involving the acoustic properties of the habitats, population genetics and a larger number of populations is required to fully understand this pattern of call variation.

Opposite effects of androgen receptor CAG repeat length on increased risk of left-handedness in males and females

Prenatal exposure to testosterone has been hypothesised to effect lateralization by influencing cell death in the foetal brain. Testosterone binds to the X chromosome linked androgen receptor, which contains a polymorphic polyglutamine CAG repeat, the length of which is positively correlated with testosterone levels in males, and negatively correlated in females. To determine whether the length of the androgen receptor mediates the effects of testosterone on laterality, we examined the association between the number of CAG repeats in the androgen receptor gene and handedness for writing. Association was tested by adding regression terms for the length of the androgen receptor alleles to a multi-factorial-threshold model of liability to left-handedness. In females we found the risk of left-handedness was greater in those with a greater number of repeats (p=0.04), this finding was replicated in a second independent sample of female twins (p=0.014). The length of the androgen receptor explained 6% of the total variance and 24% of the genetic variance in females. In males the risk of left-handedness was greater in those with fewer repeats (p=0.02), with variation in receptor length explaining 10% of the total variance and 24% of the genetic variance. Thus, consistent with Witelson's theory of testosterone action, in all three samples the likelihood of left handedness increased in those individuals with variants of the androgen receptor associated with lower testosterone levels.

A linkage study of academic skills defined by the Queensland Core Skills Test

This study used genome-wide linkage analysis to detect Quantitative Trait Loci (QTLs) implicated in variation in general academic achievement as measured by the Queensland Core Skills Test (QCST) (Queensland Studies Authority, 2004). Data from 210 families were analysed. While no empirically derived significant or suggestive peaks for general academic achievement were indicated a peak on chromosome 2 was observed in a region where Posthuma et al. (2005) reported significant linkage for Performance IQ (PIQ) and suggestive linkage for Full Scale IQ (FSIQ), and Luciano et al. (this issue) observed significant linkage for PIQ and word reading. A peak on chromosome 18 was also observed approximately 20 cM removed from a region recently implicated in reading achievement. In addition, on chromosomes 2 and 18 peaks for a number of specific academic skills, two of which were suggestive, coincided with the general academic achievement peaks. The findings suggest that variation in general academic achievement is influenced by genes on chromosome 2 which have broad influence on a variety of cognitive abilities.

Does nephron number matter in the development of kidney disease?

The total number of nephrons in normal human kidneys varies over a 10-fold range. This variation in total nephron number leads us to question whether low nephron number increases the risk of renal disease in adulthood. This review considers the available evidence in humans linking low nephron number/reduced nephron endowment and the susceptibility to renal disease. Total nephron number in humans has been directly correlated with birth weight and inversely correlated with age, mean glomerular volume, and hypertension. Low nephron number may be the result of suboptimal nephrogenesis during kidney development and/or loss of nephrons once nephrogenesis has been completed. Low nephron number is frequently, but not always, associated with hypertrophy of remaining glomeruli. This compensatory hypertrophy has also been associated with a greater susceptibility for kidney disease. Three human studies have reported reduced nelphron number in subjects with a history of hypertension. This correlation has been observed in White Europeans, White Americans (but not African Americans) and Australian Aborigines. Studies in additional populations are required, as well as a greater understanding of the fetal environmental and genetic determinants of low nephron number.

Effect of sequence variation in Plasmodium falciparum Histidine-Rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria

This Article Right arrow Full Text Right arrow Full Text (PDF) Right arrow Supplemental material Right arrow Alert me when this article is cited Right arrow Alert me if a correction is posted Services Right arrow Similar articles in this journal Right arrow Similar articles in PubMed Right arrow Alert me to new issues of the journal Right arrow Download to citation manager Right arrow Reprints and Permissions Right arrow Copyright Information Right arrow Books from ASM Press Right arrow MicrobeWorld Citing Articles Right arrow Citing Articles via HighWire Right arrow Citing Articles via Google Scholar Google Scholar Right arrow Articles by Lee, N. Right arrow Articles by McCarthy, J. Right arrow Search for Related Content PubMed Right arrow PubMed Citation Right arrow Articles by Lee, N. Right arrow Articles by McCarthy, J. Right arrow Pubmed/NCBI databases * Substance via MeSH Previous Article | Next Article Journal of Clinical Microbiology, August 2006, p. 2773-2778, Vol. 44, No. 8 0095-1137/06/$08.00+0 doi:10.1128/JCM.02557-05 Copyright © 2006, American Society for Microbiology. All Rights Reserved. Effect of Sequence Variation in Plasmodium falciparum Histidine- Rich Protein 2 on Binding of Specific Monoclonal Antibodies: Implications for Rapid Diagnostic Tests for Malaria{dagger} Nelson Lee,1,2 Joanne Baker,2 Kathy T. Andrews,1 Michelle L. Gatton,1,3 David Bell,4 Qin Cheng,2,3 and James McCarthy1* Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and School of Population Health, University of Queensland, Queensland, Australia,1 Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia,2 Malaria Drug Resistance and Chemotherapy, Queensland Institute of Medical Research, Queensland, Australia,3 World Health Organization, Regional Office for the Western Pacific, Manila, Philippines4 Received 8 December 2005/ Returned for modification 23 February 2006/ Accepted 26 May 2006 The ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparum isolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities

Extraordinary number of gene rearrangements in the mitochondrial genomes of lice (Phthiraptera : Insecta)

The arrangement of genes in the mitochondrial (mt) genomes of most insects is the same, or near-identical, to that inferred to be ancestral for insects. We sequenced the entire mt genome of the small pigeon louse, Campanulotes bidentatus compar, and part of the mt genomes of nine other species of lice. These species were from six families and the three main suborders of the order Phthiraptera. There was no variation in gene arrangement among species within a family but there was much variation in gene arrangement among the three suborders of lice. There has been an extraordinary number of gene rearrangements in the mitochondrial genomes of lice!

Familial aggregation of human infection with Schistosoma japonicum in the Poyang Lake region, China

Despite the success of extensive control measures that have been implemented in China for over 50 years, the number of individuals infected with Schistosoma japonicum remains high in the existing endemic areas. A variance components analysis was undertaken to estimate the heritable and environmental components that contribute to S. japonicum infection in the Poyang Lake region of Jiangxi Province, PR China. The total target population was 3148 from four separate administrative villages. Two thousand seven hundred and five of these comprised 400 families ranging in size from 3 to 188. After adjustments were made for gender, water contact and past history of having had schistosomiasis, the heritable component was estimated to account for as much as 58% of the phenotype variation under the polygenic model. Household was not shown to be an important environmental factor. Incorporating village effects indicated that the results were valid for the total population. We conclude that genetic heritability in this region is high and plays an important role in determining risk of infection with S. japonicum. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Genotypic variation for cold tolerance during reproductive development in rice: Screening with cold air and cold water

Rice (Oryza sativa L.) plants are susceptible to low temperature during the young microspore stage, which occurs 10-12 days before heading. Low temperature at this time increases spikelet sterility which can cause massive yield loss. Increasing the cold tolerance of cultivars can reduce yield variability in temperate rice-growing environments. Two experiments were conducted in cold air screenings and two were conducted in cold water screenings to examine genotypic variation for cold tolerance, explore flowering traits related to spikelet sterility, and investigate whether the results reflect the level of cold tolerance determined previously in the field. Cold air screenings imposed day/night temperatures of 27 degrees C/13 degrees C, 25 degrees C/15 degrees C and 32 degrees C/25 degrees C following particle initiation until 50% heading, while cold water screenings maintained a relatively constant 19 degrees C. The variation in the commencement of low air temperature treatment did not have an effect on the level of spikelet sterility, indicating that exposure to low temperature during the young microspore stage was more important than the duration of exposure. Spikelet sterility of common cultivars showed a significant correlation between cold air and cold water screenings (r(2) = 0.63, p < 0.01), cold air and field screenings (r(2) = 0.52, p < 0.01) and cold water and field screenings (r(2) = 0.53, p < 0.01), indicating that cold air and cold water can be used for screening genotypes for low temperature tolerance. HSC55, M 103 and Jyoudeki were identified as cold tolerant and Doongara, Sasanishiki and Nipponbare as susceptible cultivars. There was a significant negative relationship between spikelet sterility and both the number of engorged pollen grains per anther and anther area only after imposing cold air and cold water treatment hence, it was concluded that these flowering traits were facultative in nature. In addition, cultivars originating from Australia and California were inefficient at producing filled grain with similar sized anthers containing a similar number of engorged pollen grains as cultivars from other origins. One suggested reason for this poor conversion to filled grain of cultivars from Australia and California may be associated with their small stigma area, particularly when exposed to low temperature conditions. (c) 2006 Elsevier B.V. All rights reserved.

Minimising cold damage during reproductive development among temperate rice genotypes. II. Genotypic variation and flowering traits related to cold tolerance screening

Low temperature during microspore development increases spikelet sterility and reduces grain yield in rice (Oryza sativa L.). The objectives of this study were to determine genotypic variation in spikelet sterility in the field in response to low-temperature and then to examine the use of physio-morphological traits at flowering to screen for cold tolerance. Multiple-sown field experiments were conducted over 4 consecutive years in the rice-growing region of Australia to increase the likelihood of encountering low-temperature during microspore development. More than 50 cultivars of various origins were evaluated, with 7 cultivars common to all 4 years. The average minimum temperature for 9 days during microspore development was used as a covariate in the analysis to compare cultivars at a similar temperature. The low-temperature conditions in Year 4 identified cold-tolerant cultivars such as Hayayuki and HSC55 and susceptible cultivars such as Sasanishiki and Doongara. After low temperature conditions, spikelet sterility was negatively correlated with the number of engorged pollen grains, anther length, anther area, anther width, and stigma area. The number of engorged pollen grains and anther length were found to be facultative traits as their relationships with spikelet sterility were identified only after cold water exposure and did not exist under non-stressed conditions.