Publications by authors named "Christine Bird"

20 Publications

  • Page 1 of 1

Going against the Norm: A Mixed Methods Analysis of College Students' Arguments against the College Drinking Culture.

Subst Use Misuse 2021 Sep 27:1-10. Epub 2021 Sep 27.

Department of Psychology, Niagara University, Niagara, New York, USA.

Objective: College alcohol beliefs (e.g. "College is a time for experimentation with alcohol") are highly predictive of heavy drinking and its consequences. Yet, current college alcohol interventions do not address this belief system even though researchers have recommended that these beliefs be targeted.

Method: Using a mixed methods approach, we conducted two studies to generate arguments against the college drinking culture and to evaluate the effectiveness of such arguments.

Results: In Study 1, freshman students ( = 104, 65% women) wrote an essay to a fictitious roommate presenting arguments against the college drinking culture. Responses were reliably coded into a 19-category scheme. The most common arguments included that (1) one's focus should be on academics, (2) drinking will lead to academic consequences, and (3) drinking is not a rite of passage in college. In Study 2, college students ( = 488) rated the effectiveness of prototype arguments drawn from each Study 1 category. According to their ratings, the most effective arguments were that (1) one's focus should be on academics, (2) drinking could have a negative impact on one's career, and (3) one could do potential harm to others.

Conclusions: The student-generated arguments against the college drinking culture identified in his research have inherent ecological validity and will help inform the development of new interventions to counter such beliefs. We offer suggestions for translating our findings into clinical interventions.The problem of college student drinking has been long-standing (Kilmer et al., 2014) and remains a significant public health issue today (Hingson et al., 2017). Decades of research on college student drinking and its consequences have identified key cognitive factors that underlie drinking and its consequences, such as the misperception of norms for drinking (Borsari & Carey, 2003) and the positive expectancies students hold about the effects of drinking (Jones et al., 2001; Monk & Heim, 2013). The robust relationships between these cognitive variables and alcohol consumption among college students have led to the development of interventions that target these variables. Social norms marketing campaigns (DeJong et al., 2006), personalized normative feedback (Lewis & Neighbors, 2006), and expectancy challenge techniques (Scott-Sheldon et al., 2012) have been a part of interventions designed to correct students' misperceptions about the percentage of and amount students drink and the effects that alcohol has on their functioning in social situations. Reviews of the literature have demonstrated that interventions containing these components are effective for first year students (Scott-Sheldon et al., 2014) and mandated students (Carey et al., 2016), except for interventions targeting student members of Greek letter organizations (Scott-Sheldon et al., 2016). Effect sizes in most interventions across freshman and mandated students tend to be modest and not very durable in the long-term (Carey et al., 2016; Scott-Sheldon et al., 2014). However, recent research reveals that a variety of new intervention strategies may be useful in addressing the problem of college student drinking (Dunn et al., 2020; Kazemi et al., 2020; King et al., 2020; Magill et al., 2017; Pedrelli et al., 2020; Young & Neighbors, 2019). Aside from social norms and positive alcohol expectancies, another cognitive variable has been found to be a very robust predictor, mediator, and moderator of college student drinking and its consequences - (Crawford & Novak, 2006; Osberg et al., 2010).
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http://dx.doi.org/10.1080/10826084.2021.1981392DOI Listing
September 2021

Accuracy of Home-Based Ultrasonographic Diagnosis of Obstetric Risk Factors by Primary-Level Health Care Workers in Rural Nepal.

Obstet Gynecol 2016 09;128(3):604-612

Johns Hopkins Bloomberg School of Public Health, and the Johns Hopkins Hospital, Baltimore, Maryland; the Nepal Nutrition Intervention Project-Sarlahi, Lalitpur, and Tribhuvan University Teaching Hospital, Kathmandu, Nepal; and George Washington University Milken Institute School of Public Health, Washington, DC.

Objective: To assess the feasibility of ultrasonographic task shifting by estimating the accuracy at which primary-level health care workers can perform community-based third-trimester ultrasound diagnosis for selected obstetric risk factors in rural Nepal.

Methods: Three auxiliary nurse-midwives received two 1-week ultrasound trainings at Tribhuvan University Teaching Hospital in Kathmandu. At a study site in rural Nepal, pregnant women who were 32 weeks of gestation or greater were enrolled and received ultrasound examinations from the auxiliary nurse-midwives during home visits. Each auxiliary nurse-midwife screened for noncephalic presentation, multiple gestation, and placenta previa. Deidentified digital ultrasonograms were stored and uploaded onto an online server, where certified sonologists and ultrasonographers reviewed the images and made their own diagnoses for the three conditions. Accuracy of auxiliary nurse-midwife diagnoses was then calculated.

Results: A total of 804 women contributed to the analysis. Each auxiliary nurse-midwife's κ statistic for diagnosis of noncephalic presentation was above 0.90 compared with the ultrasonogram reviewers. Sensitivity, specificity, and positive and negative predictive values were between 90% and 100% for all auxiliary nurse-midwives. For multiple gestation, the auxiliary nurse-midwives were in perfect agreement with both the ultrasonogram reviewers and maternal postpartum self-report. Two placenta previa cases were detected, and the ultrasonogram reviewers agreed with both.

Conclusion: With limited training, primary-level health care workers in rural Nepal can accurately diagnose selected third-trimester obstetric risk factors using ultrasonography.
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http://dx.doi.org/10.1097/AOG.0000000000001558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028110PMC
September 2016

The zebrafish reference genome sequence and its relationship to the human genome.

Nature 2013 Apr 17;496(7446):498-503. Epub 2013 Apr 17.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
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http://dx.doi.org/10.1038/nature12111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927PMC
April 2013

Mutation spectrum revealed by breakpoint sequencing of human germline CNVs.

Nat Genet 2010 May 4;42(5):385-91. Epub 2010 Apr 4.

Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

Precisely characterizing the breakpoints of copy number variants (CNVs) is crucial for assessing their functional impact. However, fewer than 10% of known germline CNVs have been mapped to the single-nucleotide level. We characterized the sequence breakpoints from a dataset of all CNVs detected in three unrelated individuals in previous array-based CNV discovery experiments. We used targeted hybridization-based DNA capture and 454 sequencing to sequence 324 CNV breakpoints, including 315 deletions. We observed two major breakpoint signatures: 70% of the deletion breakpoints have 1-30 bp of microhomology, whereas 33% of deletion breakpoints contain 1-367 bp of inserted sequence. The co-occurrence of microhomology and inserted sequence is low (10%), suggesting that there are at least two different mutational mechanisms. Approximately 5% of the breakpoints represent more complex rearrangements, including local microinversions, suggesting a replication-based strand switching mechanism. Despite a rich literature on DNA repair processes, reconstruction of the molecular events generating each of these mutations is not yet possible.
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http://dx.doi.org/10.1038/ng.564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428939PMC
May 2010

Genome-wide detection and characterization of positive selection in human populations.

Nature 2007 Oct;449(7164):913-8

Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA.

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.
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http://dx.doi.org/10.1038/nature06250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687721PMC
October 2007

A second generation human haplotype map of over 3.1 million SNPs.

Nature 2007 Oct;449(7164):851-61

The Scripps Research Institute, 10550 North Torrey Pines Road MEM275, La Jolla, California 92037, USA.

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.
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http://dx.doi.org/10.1038/nature06258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689609PMC
October 2007

Islands of euchromatin-like sequence and expressed polymorphic sequences within the short arm of human chromosome 21.

Genome Res 2007 Nov 25;17(11):1690-6. Epub 2007 Sep 25.

Department of Genetic Medicine and Development, University of Geneva Medical School, and University Hospitals, 1211 Geneva, Switzerland.

The goals of the human genome project did not include sequencing of the heterochromatic regions. We describe here an initial sequence of 1.1 Mb of the short arm of human chromosome 21 (HSA21p), estimated to be 10% of 21p. This region contains extensive euchromatic-like sequence and includes on average one transcript every 100 kb. These transcripts show multiple inter- and intrachromosomal copies, and extensive copy number and sequence variability. The sequencing of the "heterochromatic" regions of the human genome is likely to reveal many additional functional elements and provide important evolutionary information.
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http://dx.doi.org/10.1101/gr.6675307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2045151PMC
November 2007

Population genomics of human gene expression.

Nat Genet 2007 Oct 16;39(10):1217-24. Epub 2007 Sep 16.

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Genetic variation influences gene expression, and this variation in gene expression can be efficiently mapped to specific genomic regions and variants. Here we have used gene expression profiling of Epstein-Barr virus-transformed lymphoblastoid cell lines of all 270 individuals genotyped in the HapMap Consortium to elucidate the detailed features of genetic variation underlying gene expression variation. We find that gene expression is heritable and that differentiation between populations is in agreement with earlier small-scale studies. A detailed association analysis of over 2.2 million common SNPs per population (5% frequency in HapMap) with gene expression identified at least 1,348 genes with association signals in cis and at least 180 in trans. Replication in at least one independent population was achieved for 37% of cis signals and 15% of trans signals, respectively. Our results strongly support an abundance of cis-regulatory variation in the human genome. Detection of trans effects is limited but suggests that regulatory variation may be the key primary effect contributing to phenotypic variation in humans. We also explore several methodologies that improve the current state of analysis of gene expression variation.
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http://dx.doi.org/10.1038/ng2142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683249PMC
October 2007

Fast-evolving noncoding sequences in the human genome.

Genome Biol 2007 ;8(6):R118

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK.

Background: Gene regulation is considered one of the driving forces of evolution. Although protein-coding DNA sequences and RNA genes have been subject to recent evolutionary events in the human lineage, it has been hypothesized that the large phenotypic divergence between humans and chimpanzees has been driven mainly by changes in gene regulation rather than altered protein-coding gene sequences. Comparative analysis of vertebrate genomes has revealed an abundance of evolutionarily conserved but noncoding sequences. These conserved noncoding (CNC) sequences may well harbor critical regulatory variants that have driven recent human evolution.

Results: Here we identify 1,356 CNC sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated CNC' (ANC) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within ANC sequences have a significant excess of high frequency derived alleles and high F(ST) values relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within ANC sequences are associated with changes in gene expression. The probability of variation in an ANC sequence being associated with a gene expression phenotype is fivefold higher than variation in a control CNC sequence.

Conclusion: Our analysis suggests that ANC sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation.
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http://dx.doi.org/10.1186/gb-2007-8-6-r118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394770PMC
February 2008

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

Nature 2007 Jun;447(7146):799-816

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212820PMC
http://dx.doi.org/10.1038/nature05874DOI Listing
June 2007

Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials.

Chromosome Res 2007 5;15(2):127-36. Epub 2007 Mar 5.

Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Department, Novosibirsk, Russia.

X inactivation, the transcriptional silencing of one of the two X chromosomes in female mammals, achieves dosage compensation of X-linked genes relative to XY males. In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed. Marsupial mammals also undergo X inactivation but the mechanism is relatively poorly understood. We set out to analyse the X chromosome in Monodelphis domestica and Didelphis virginiana, focusing on characterizing the interval defined by the Chic1 and Slc16a2 genes that in eutherians flank the Xist locus. The synteny of this region is retained on chicken chromosome 4 where other loci belonging to the evolutionarily ancient stratum of the human X chromosome, the so-called X conserved region (XCR), are also located. We show that in both M. domestica and D. virginiana an evolutionary breakpoint has separated the Chic1 and Slc16a2 loci. Detailed analysis of opossum genomic sequences revealed linkage of Chic1 with the Lnx3 gene, recently proposed to be the evolutionary precursor of Xist, and Fip1, the evolutionary precursor of Tsx, a gene located immediately downstream of Xist in eutherians. We discuss these findings in relation to the evolution of Xist and X inactivation in mammals.
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http://dx.doi.org/10.1007/s10577-006-1115-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797855PMC
June 2007

Relative impact of nucleotide and copy number variation on gene expression phenotypes.

Science 2007 Feb;315(5813):848-53

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.

Extensive studies are currently being performed to associate disease susceptibility with one form of genetic variation, namely, single-nucleotide polymorphisms (SNPs). In recent years, another type of common genetic variation has been characterized, namely, structural variation, including copy number variants (CNVs). To determine the overall contribution of CNVs to complex phenotypes, we have performed association analyses of expression levels of 14,925 transcripts with SNPs and CNVs in individuals who are part of the International HapMap project. SNPs and CNVs captured 83.6% and 17.7% of the total detected genetic variation in gene expression, respectively, but the signals from the two types of variation had little overlap. Interrogation of the genome for both types of variants may be an effective way to elucidate the causes of complex phenotypes and disease in humans.
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http://dx.doi.org/10.1126/science.1136678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665772PMC
February 2007

Functional variation and evolution of non-coding DNA.

Curr Opin Genet Dev 2006 Dec 19;16(6):559-64. Epub 2006 Oct 19.

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.

The focus of large genomic studies has shifted from only looking at genes and protein-coding sequences to exploring the full set of elements in each genome. The explosion of comparative sequencing data has led to an increase in methodologies, approaches and ideas on how to analyze the unknown fraction of the genome, namely the non-protein-coding fraction. The main issues relate to the discovery, evolutionary analysis and natural variation of non-coding DNA, and the parameters that prevent us from fully understanding the properties of non-coding DNA.
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http://dx.doi.org/10.1016/j.gde.2006.10.003DOI Listing
December 2006

Conserved noncoding sequences are selectively constrained and not mutation cold spots.

Nat Genet 2006 Feb 25;38(2):223-7. Epub 2005 Dec 25.

Program in Genomics and Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA.

Noncoding genetic variants are likely to influence human biology and disease, but recognizing functional noncoding variants is difficult. Approximately 3% of noncoding sequence is conserved among distantly related mammals, suggesting that these evolutionarily conserved noncoding regions (CNCs) are selectively constrained and contain functional variation. However, CNCs could also merely represent regions with lower local mutation rates. Here we address this issue and show that CNCs are selectively constrained in humans by analyzing HapMap genotype data. Specifically, new (derived) alleles of SNPs within CNCs are rarer than new alleles in nonconserved regions (P = 3 x 10(-18)), indicating that evolutionary pressure has suppressed CNC-derived allele frequencies. Intronic CNCs and CNCs near genes show greater allele frequency shifts, with magnitudes comparable to those for missense variants. Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation.
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http://dx.doi.org/10.1038/ng1710DOI Listing
February 2006

Progressive proximal expansion of the primate X chromosome centromere.

Proc Natl Acad Sci U S A 2005 Jul 19;102(30):10563-8. Epub 2005 Jul 19.

Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the functional centromere. We analyzed the finished sequence of this human genomic region to investigate its evolutionary history. Phylogenetic analysis of >1,500 alpha-satellite monomers from the region revealed the presence of five physical domains, each containing monomers from a distinct phylogenetic clade. The most distal domain contains long interspersed nucleotide element repeats that were active >35 million years ago, whereas the four proximal domains contain more recently active long interspersed nucleotide element repeats. An out-of-register, unequal recombination (i.e., crossover) detected at the edge of the X chromosome-specific alpha-satellite array (DXZ1) may reflect the most recent of a series of punctuating events during evolution that resulted in a proximal physical expansion of the X centromere. The first 18 kb of this array has 97-99% pairwise identity among all 2-kb repeat units. To perform more detailed evolutionary comparisons, we sequenced the junction between the ancient DNA of Xp and the primate-specific alpha satellite in chimpanzee, gorilla, orangutan, vervet, macaque, and baboon. The striking conservation found in all cases supports the ancestral nature of the alpha satellite at this location. These studies demonstrate that the primate X centromere appears to have evolved through repeated expansion events occurring within the central, active region of centromeric DNA, with the newly added sequences then conferring centromere function.
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http://dx.doi.org/10.1073/pnas.0503346102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180780PMC
July 2005

The DNA sequence of the human X chromosome.

Nature 2005 Mar;434(7031):325-37

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
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http://dx.doi.org/10.1038/nature03440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665286PMC
March 2005

Complete nucleotide sequence of the conjugative tetracycline resistance plasmid pFBAOT6, a member of a group of IncU plasmids with global ubiquity.

Appl Environ Microbiol 2004 Dec;70(12):7497-510

Centre for Ecology and Hydrology, Lancaster, United Kingdom.

This study presents the first complete sequence of an IncU plasmid, pFBAOT6. This plasmid was originally isolated from a strain of Aeromonas caviae from hospital effluent (Westmorland General Hospital, Kendal, United Kingdom) in September 1997 (G. Rhodes, G. Huys, J. Swings, P. McGann, M. Hiney, P. Smith, and R. W. Pickup, Appl. Environ. Microbiol. 66:3883-3890, 2000) and belongs to a group of related plasmids with global ubiquity. pFBAOT6 is 84,748 bp long and has 94 predicted coding sequences, only 12 of which do not have a possible function that has been attributed. Putative replication, maintenance, and transfer functions have been identified and are located in a region in the first 31 kb of the plasmid. The replication region is poorly understood but exhibits some identity at the protein level with replication proteins from the gram-positive bacteria Bacillus and Clostridium. The mating pair formation system is a virB homologue, type IV secretory pathway that is similar in its structural organization to the mating pair formation systems of the related broad-host-range (BHR) environmental plasmids pIPO2, pXF51, and pSB102 from plant-associated bacteria. Partitioning and maintenance genes are homologues of genes in IncP plasmids. The DNA transfer genes and the putative oriT site also exhibit high levels of similarity with those of plasmids pIPO2, pXF51, and pSB102. The genetic load region encompasses 54 kb, comprises the resistance genes, and includes a class I integron, an IS630 relative, and other transposable elements in a 43-kb region that may be a novel Tn1721-flanked composite transposon. This region also contains 24 genes that exhibit the highest levels of identity to chromosomal genes of several plant-associated bacteria. The features of the backbone of pFBAOT6 that are shared with this newly defined group of environmental BHR plasmids suggest that pFBAOT6 may be a relative of this group, but a relative that was isolated from a clinical bacterial environment rather than a plant-associated bacterial environment.
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http://dx.doi.org/10.1128/AEM.70.12.7497-7510.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC535204PMC
December 2004

BAC finishing strategies.

Methods Mol Biol 2004 ;255:255-77

Welcome Trust Genome Campus, The Sanger Institute, Cambridge, UK.

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http://dx.doi.org/10.1385/1-59259-752-1:255DOI Listing
May 2004

Dispersal of NK homeobox gene clusters in amphioxus and humans.

Proc Natl Acad Sci U S A 2003 Apr 18;100(9):5292-5. Epub 2003 Apr 18.

School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom.

The Drosophila melanogaster genome has six physically clustered NK-related homeobox genes in just 180 kb. Here we show that the NK homeobox gene cluster was an ancient feature of bilaterian animal genomes, but has been secondarily split in chordate ancestry. The NK homeobox gene clusters of amphioxus and vertebrates are each split and dispersed at two equivalent intergenic positions. From the ancestral NK gene cluster, only the Tlx-Lbx and NK3-NK4 linkages have been retained in chordates. This evolutionary pattern is in marked contrast to the Hox and ParaHox gene clusters, which are compact in amphioxus and vertebrates, but have been disrupted in Drosophila.
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http://dx.doi.org/10.1073/pnas.0836141100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC154338PMC
April 2003

Comparative and functional analyses of LYL1 loci establish marsupial sequences as a model for phylogenetic footprinting.

Genomics 2003 Mar;81(3):249-59

Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Hills Road, Cambridge CB2 2XY, UK.

Comparative genomic sequence analysis is a powerful technique for identifying regulatory regions in genomic DNA. However, its utility largely depends on the evolutionary distances between the species involved. Here we describe the screening of a genomic BAC library from the stripe-faced dunnart, Sminthopsis macroura, formerly known as the narrow-footed marsupial mouse. We isolated a clone containing the LYL1 locus, completely sequenced the 60.6-kb insert, and compared it with orthologous human and mouse sequences. Noncoding homology was substantially reduced in the human/dunnart analysis compared with human/mouse, yet we could readily identify all promoters and exons. Human/mouse/dunnart alignments of the LYL1 candidate promoter allowed us to identify putative transcription factor binding sites, revealing a pattern highly reminiscent of critical regulatory regions of the LYL1 paralogue, SCL. This newly identified LYL1 promoter showed strong activity in myeloid progenitor cells and was bound in vivo by Fli1, Elf1, and Gata2-transcription factors all previously shown to bind to the SCL stem cell enhancer. This study represents the first large-scale comparative analysis involving marsupial genomic sequence and demonstrates that such comparisons provide a powerful approach to characterizing mammalian regulatory elements.
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http://dx.doi.org/10.1016/s0888-7543(03)00005-3DOI Listing
March 2003
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