bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of improved housing on illness in children under 5‐year‐old in northern Malawi: cross sectional study.
Authors: Reading Richard 
Published: March 2003

Objective To evaluate the effects of a Habitat for Humanity housing improvement programme in northern Malawi on the prevalence of childhood illnesses.Design Household‐based cross‐sectional study.Setting Rural communities centred near the small northern Malawi town of Ekwendeni.Subjects A total of 318 children under 5 years old.Main outcome measures Prevalence of respiratory, gastrointestinal and malarial infections according to maternal recall, laboratory, or clinical data.Results Children living in improved homes were less likely to have respiratory, gastrointestinal, or malarial illnesses (odds ratio 0.56, 95% confidence interval 0.35–0.91) after confounding factors were controlled for. The reductions in individual diseases were not significant.Conclusion Improved housing significantly reduced the burden of disease among children under 5 years old.
A review of Dysgenics: Genetic Deterioration in Modern Populations
Authors: HAMILTON W. D. 
Published: March 2003

Editorial Note This book review arrived here at the beginning of this year with a very apologetic note from the author, Bill Hamilton, about the long delay in producing the review and its ‘rambling essay format’. Sadly, Hamilton died just a few weeks later from complications following malarial infection. Several tributes have been published, such as Science (2000), 287, 2438, and we continue the tributes with a final unedited manuscript from the hand of this unique, colourful and idiosyncratic evolutionary theorist. Dysgenics: Genetic Deterioration in Modern Populations. Human Evolution, Behaviour, and Intelligence Series. By R. Lynn (Series Editor: S. Itzkoff). Westport, Connecticut and London: Praeger. 1996. Pp. 237. £47.50 (hardback).In a sense a dominance hierarchy has only one satisfied individual – she or he at the top. If the hierarchy is bottom‐numerous rather than linear, as is the case with most human hierarchies, it is all the more true that the vast majority of people are dissatisfied, wishing they were higher up, a thought which provides a basic reason why democracies (and especially, within democracies, such institutions as their state school systems) have to be unstable. We see a wobbly pyramid, and particularly within that pyramid we see certain side stairs all human examples have by which demagogues skip up a level or two so as to shout down to the restless base that the whole structure is somehow ‘wrong’. Under a different system, the demagogue shouts, ‘You could be higher too’.
A genome‐wide family‐based linkage study of coeliac disease
Authors: KING A. L. , YIANNAKOU J. Y. , BRETT P. M. , CURTIS D. , MORRIS M.‐A. , DEARLOVE A. M. , RHODES M. , ROSEN‐BRONSON S. , MATHEW C. , ELLIS H. J. , CICLITIRA P. J. 
Published: March 2003

The susceptibility to develop coeliac disease (CD) has a strong genetic component, which is not entirely explained by HLA associations. Two previous genome wide linkage studies have been performed to identify additional loci outside this region. These studies both used a sib‐pair design and produced conflicting results.Our aim is to identify non‐MHC genetic loci contributing to coeliac disease using a family based linkage study. We performed a genome wide search in 16 highly informative multiply affected pedigrees using 400 microsatellite markers with an average spacing of 10 cM. Linkage analysis was performed using lod score and model free methods.We identified two new potential susceptibility loci with lod scores of 1.9, at 10q23.1, and 16q23.3. Significant, but lower lod scores were found for 6q14 (1.2), 11p11 (1.5), and 19q13.4 (0.9), areas implicated in a previous genome wide study. Lod scores of 0.9 were obtained for both D7S507, which lies 1 cM from the γT‐cell receptor gene, and for D2S364, which lies 12 cM from the CTLA4 gene.
Sampling distribution of summary linkage disequilibrium measures
Authors: TEARE M. D. , DUNNING A. M. , DUROCHER F. , RENNART G. , 3EASTON D. F. 
Published: March 2003

The design of association studies is critically dependent upon the extent of linkage disequilibrium (LD) across different genomic regions, often summarised in terms of the mean absolute value of summary linkage disequilibrium measures. The two most commonly used measures are D′ for estimating the magnitude or extent of LD, and Δ which is directly proportional to the power of LD mapping.We studied the sampling distribution of the mean of ∣D^′∣ and ∣Δ^∣ statistics for varying sample size and major allele frequencies. When the sample size is small or one allele frequency is extreme, estimates of the magnitude of association based on the mean of ∣D^′∣ can be substantially inflated. This inflation is more marked when the haplotype frequencies have been inferred from genotype counts. The net effect of this means that smaller studies will tend to show higher levels of LD. The magnitude of this inflation can be reduced by use of a bootstrap correction, and by avoiding using markers with extreme allele frequencies. In contrast, the ∣Δ^∣ statistic is much less affected by sample size and high major allele frequencies. These effects are illustrated with real data on 36 SNPs typed in an Ashkenasi Jewish population.
Interaction between smoking and the stromelysin‐1 (MMP3) gene 5A/6A promoter polymorphism and risk of coronary heart disease in healthy men
Authors: HUMPHRIES S. E. , MARTIN S. , COOPER J. , MILLER G. 
Published: March 2003

Smoking is a major risk factor for coronary heart disease (CHD), but this risk may be modified by an individual's genotype. A common functional 5A/6A polymorphism in the promoter of the stromelysin‐1 (matrix metalloproteinase 3, MMP3) gene has been identified. The 6A allele has been consistently associated with faster progression of angiographically determined CHD, while the 5A allele has recently been associated with risk of acute myocardial infarction (MI) in patients with unstable angina. To date there has been no prospective study of the relationship of this genotype to CHD risk in smokers and non‐smokers.DNA was available from 2743 middle‐aged men, free of CHD at baseline, recruited through nine general practices in the UK for prospective surveillance. To date there have been almost 24000 person‐years of follow‐up with 125 CHD events (fatal and non‐fatal MI, sudden coronary death, need for coronary artery surgery or new major ECG Q‐wave abnormality). Men with events were each matched for age, practice and cholesterol level with three healthy men. Smoking habit was determined by questionnaire. 5A/6A genotype was determined using a heteroduplex generator method. Associations between genotype and disease outcome, according to smoking status, were assessed using conditional logistic regression. Overall, current smoking was associated with a relative risk (RR) of 1.99 (95% CI 1.30–3.06) as compared with never‐smokers and ex‐smokers combined (p<0.002). In non‐smoking men, and after adjustment for conventional risk factors, compared with the 5A5A group, the RR was 1.37 (0.64–2.94) in those with the genotype 5A6A and 3.02 (1.38–6.61) in those with the genotype 6A6A. Smoking increased risk 1.4 fold in the 5A6A group to 1.91 (1.84–4.36), by 1.3 fold in the 6A6A group to 4.01 (1.57–10.24), but by 3.81 fold (1.54–9.40) in the 5A5A group (smoking–genotype interaction p = 0.01). The data indicate a key role for stromelysin in the atherosclerotic process. Men with the stromelysin genotype 5A5A represent 29% of the general population, and their high risk, if smokers, provides a further strong argument for smoking avoidance.
Haplotype Structure of TP53 Locus in Indian Population and Possible Association with Head and Neck Cancer
Authors: Mitra S. , Chatterjee S , Panda C. K. , Chaudhuri K. , Ray K. , Bhattacharyya N. P. , Sengupta A. , Roychoudhury S. 
Published: March 2003

SummaryIt has been proposed that a constellation of three TP53 polymorphisms (intron 3 16 bp duplication, codon 72 BstUI, and intron 6 Nci I RFLP at nt 13494) constitute a haplotype predictive of increased cancer risk. We have estimated the allele frequency of these polymorphisms in three endogamous Indian ethnic populations from three different geographic locations (viz. Iyer from south India, Brahmin from central India and Mahishya from eastern India), as well as in head and neck squamous cell carcinoma (HNSCC) patients, and in ethnically matched normal individuals from the eastern region of India. The genotype distributions and allele frequencies of the three polymorphisms in all but one population, as well as in patients, showed a good fit to Hardy‐Weinberg equilibrium. Strong linkage disequilibria were observed between all loci in every population examined, except for the 16bp‐Nci I haplotype in the Mahishya population. The Mahishya population differed significantly from the other two populations with respect to differences in allele frequency and haplotype frequency. Although there were no significant differences in genotypic frequency at any of the loci between HNSCC patients and the matched control population, the minor allele frequency of codon 72 and intron 3 16 bp polymorphisms showed significant variation. Variation in overall haplotype frequency between patients and normal individuals was significant (p = 0.036) when two rare haplotypes 2‐1‐2 and 1‐2‐1 were combined. The rare haplotype 2‐1‐2 was found to be modestly over represented in HNSCC patients as compared to normal individuals.
CARD15/NOD2 Risk Alleles in the Development of Crohn's Disease in the Australian Population
Authors: Cavanaugh J. A. , Adams K. E. , Quak E. J. , Bryce M. E. , O'Callaghan N. J. , Rodgers H. J. , Magarry G. R. , Butler W. J. , Eaden J. A. , Roberts‐Thomson I. C. , Pavli P. , Wilson S. R. , Callen D. F. 
Published: March 2003

SummaryWe have previously reported strong evidence for linkage between IBD1 and Crohn's disease (CD) in Australian Crohn's disease families. Three risk alleles for Crohn's disease, (Arg702Trp (C/T), Gly908Arg (G/C) and 980fs981 (‐/C), were recently identified in the CARD15/NOD2 gene on chromosome 16, implicating this as the IBD1 locus. Using a novel diagnostic PCR‐RFLP, we have examined the frequency of these alleles in 205 multiplex IBD families, 107 sporadic Crohn's disease cases and 409 normal individuals. We demonstrate that the three risk alleles are more frequent in Crohn's disease, than in controls, with allelic frequencies of 0.11, 0.02 and 0.07 respectively. Heterozygosity for individual variants conferred a three‐fold increase in risk for Crohn's disease while substantially higher risks were associated with being homozygous or compound heterozygous. Despite a significantly lower population allele frequency for the frameshift mutation than reported by other groups, we see a similar contribution by this allele to the risk of developing Crohn's disease. While the three risk alleles influence susceptibility to Crohn's disease in Australia, we show that these alleles do not fully explain the linkage evidence and suggest that there are very likely additional IBD1 susceptibility alleles yet to be described in Australian CD at the NOD2 locus. We also show a second linkage peak in Australian CD that provides some support for a second disease susceptibility locus on chromosome 16.
The Study ofAPOA1,APOC3andAPOA4Variability in Healthy Ageing People Reveals Another Paradox   in the Oldest Old Subjects
Authors: Garasto S. , Rose G. , Derango F. , Berardelli M. , Corsonello A. , Feraco E. , Mari V. , Maletta R. , Bruni A. , Franceschi C. , Carotenuto L. , De Benedictis G. 
Published: March 2003

SummaryThe genes coding for apolipoprotein A1 (APOA1), apolipoprotein C3 (APOC3) and apolipoprotein A4 (APOA4) are tandemly organised within a short region on chromosome 11q23‐q24. Polymorphisms of these genes have been extensively investigated in lipoprotein disorders and cardiovascular diseases, but poorly investigated in healthy ageing. The aim of this study was to describe possible modifications of theAPOA1,APOC3, andAPOA4gene pool by cross‐sectional studies carried out in a healthy ageing population whose ages ranged from 18 to 109 years (800 subjects, 327 males and 473 females, free of clinically manifested disease, and with emato‐chemical parameters in the norm).APOA1‐MspI‐RFLP (−75 nt from the transcription starting site),APOC3‐SstI‐RFLP (3′UTR, 3238 nt), andAPOA4‐HincII‐RFLP (Asp127/Ser127) were analysed according to age and sex. A significant age‐related variation of theAPOA1gene pool was observed in males. An analysis of the allele average effect exerted byAPOA1‐MspI‐RFLP A/P alleles (Absence/Presence of the restriction site) on lipidemic parameters in 46–80 year old males showed that allele A decreased, while allele P significantly increased, serum LDL‐cholesterol. Unexpectedly, the P allele was over‐represented in the group of the oldest old subjects, thus giving evidence of another “genetic paradox of centenarians”.
A Predominant European Ancestry of Paternal Lineages from Canary Islanders
Authors: Flores C. , Maca‐Meyer N. , Pérez J. A. , González A. M. , Larruga J. M. , Cabrera V. M. 
Published: March 2003

SummaryWe genotyped 24 biallelic sites and 5 microsatellites from the non‐recombining portion of the Y chromosome in 652 males from the Canary Islands. The results indicate that, contrary to mtDNA data, paternal lineages of the current population are overwhelmingly (>90%) of European origin, arguing for a highly asymmetric pattern of mating after European occupation. However, the presence of lineages of indisputable African assignation demonstrates that an aboriginal background still persists (<10%). On the basis of distribution and dating of some of these lineages we derived a genetic perspective of settlement processes of the archipelago in two stages, congruent with anthropological, archaeological and linguistic findings.
Family History is a Coronary Heart Disease Risk Factor in the Second Northwick Park Heart Study
Authors: Hawe E. , Talmud P. J. , Miller G. J. , Humphries S. E. 
Published: March 2003

SummaryWe have estimated the risk of coronary heart disease (CHD) from family history of CHD (FHCHD) in 2827 healthy European middle‐aged men, and explored the extent to which this can be explained by classical and genetic risk factors. Men with FHCHD (obtained by questionnaire) had a hazard ratio of CHD of 1.73 (95% confidence interval: 1.30, 2.31) compared to those without FHCHD; after adjusting for classical risk factors this did not change substantially. Those with FHCHD had 2.3% lower Factor VIIc (p = 0.03) and 1.14% higher systolic and 1.21% higher diastolic blood pressure (p = 0.04 and p = 0.02), with evidence of interaction between blood pressure and FHCHD status on risk (p = 0.01). The risk for those with a positive family history who were also current smokers was 3.01 compared to non‐smokers without FHCHD, which is greater than the risk posed by smoking or FHCHD alone (1.96 and 2.05 respectively compared to non‐smokers without FHCHD), but not significantly different from a multiplicative model (p‐value for interaction 0.33). Allele frequencies for 13 candidate gene variants were not significantly different between those with and without FHCHD. In those with FHCHD, current smokers who carried the APOE4 allele (e4+) had a hazard ratio of 5.66 compared to non‐smokers who had no FHCHD and were not APOE4+, with a significant interaction between smoking and APOE4 in those with FHCHD p = 0.001. These data demonstrate the complex interaction between genetic and environmental factors in determining CHD risk, and suggest that the causes of the familial clustering of CHD remain largely unexplained.
Estimation of Multilocus Haplotype Effects Using Weighted Penalised Log‐Likelihood: Analysis of Five Sequence Variations at the Cholesteryl Ester Transfer Protein Gene Locus
Authors: Tanck M. W. T. , Klerkx A. H. E. M. , Jukema J. W. , Knijff P. De , Kastelein J. J. P. , Zwinderman A. H. 
Published: March 2003

SummaryDirect analyses of haplotype effects can be used to identify those specific combinations of alleles that are associated with a specific phenotype. We introduce a method for direct haplotype analysis that solves two problems that arise when haplotypes are analysed in populations of unrelated subjects. Instead of assigning a single, most likely, haplotype pair to multiple heterozygous subjects, all haplotype pairs compatible with their genotype were determined and the posterior probabilities of these pairs were calculated using Bayes’ theorem and estimated haplotype frequencies. For the individual patients, all possible haplotype pairs were included in the statistical analysis using the posterior probabilities as weights, which were re‐estimated in an iterative process together with the haplotype effects. The second problem of unstable haplotype effect estimates, due to the numerous haplotypes and the low frequency at which some occur, was solved by assuming that haplotypes sharing the same alleles show a similar effect and that the extent of this similarity relates to the number of alleles shared. These assumptions were incorporated in a weighted log‐likelihood model by introducing a penalty, where differences in effects of similar haplotypes were penalised. UsingCETPgene haplotypes, consisting of five closely linked polymorphisms, and baseline CETP and HDL‐C concentrations from the REGRESS population, we demonstrated that the model resulted in more stable effects than estimates based on unambiguous patients only.
Cladistic Analysis of Human Apolipoprotein A4 Polymorphisms in Relation to Quantitative Plasma Lipid Risk Factors of Coronary Heart Disease
Authors: Wang G. Q. , DiPietro M. , Roeder K. , Heng C.‐K. , Bunker C. H. , Hamman R. F. , Kamboh M. I. 
Published: March 2003

SummaryGenetic variation in several genes involved in lipid metabolism is known to affect population variation in quantitative lipid risk factor profiles for coronary heart disease (CHD). The apolipoprotein A‐IV gene (APOA4) is one such candidate gene. We genotyped five polymorphisms in theAPOA4gene (codon 127, codon 130, codon347, codon 360 and 3’ VNTR) and investigated their impact on plasma lipid trait levels in three populations comprising 604 U.S. non‐Hispanic Whites (NHWs), 408 U.S. Hispanics and 708 Nigerian Blacks. Cladistic analysis was carried out to identify 5‐site haplotypes that were associated with significant phenotypic differences in each population. The distribution ofAPOA4genotypes was significantly different between ethnic groups. The Africans were monomorphic for two of the five sites (codons 130 and 360), but possess a unique 12 bp insertion that was not observed in NHWs and Hispanics. Due to linkage disequilibrium between the sites, only 6 haplotypes were observed in NHWs and Hispanics, and 4 in Africans. Several gender‐and ethnic‐specific associations between genotypes and plasma lipid traits were observed when single sites were used. Several haplotypes were identified by cladistic analysis that may carry functional mutations that affect plasma lipid trait levels.
Maternal and Paternal Lineages of the Samaritan Isolate: Mutation Rates and Time to Most Recent Common Male Ancestor
Authors: Bonné‐Tamir B. , Korostishevsky M. , Redd A. J. , Pel‐Or Y. , Kaplan M. E. , Hammer M. F. 
Published: March 2003

SummaryThe Samaritan community is a small, isolated, and highly endogamous group numbering some 650 members who have maintained extensive genealogical records for the past 13–15 generations. We performed mutation detection experiments on mitochondrial DNAs and Y chromosomes from confirmed maternal and paternal lineages to estimate mutation rates in these two haploid compartments of the genome. One hundred and twenty four DNA samples from different pedigrees (representing 200 generation links) were analyzed for the mtDNA hypervariable I and II regions, and 74 male samples (comprising 139 links) were typed for 12 Y‐STRs mapping to the non‐recombining portion of the Y chromosome (NRY). Excluding two somatic heteroplasmic substitutions and several length variants in the homopolymeric C run in the HVII region, no mutations were found in the Samaritans' maternal lineages. Based on mutations found in Samaritan paternal lineages, an estimate of a mutation rate of 0.42% (95% confidence interval of 0.22%–0.71%) across 12 Y‐STRs was obtained. This estimate is slightly higher than those obtained in previous pedigree studies in other populations. The haplotypes identified in Samaritan paternal lineages that belong to the same haplogroup were used to estimate the number of generations elapsed since their most recent common ancestor (MRCA). The estimate of 80 generations corresponds with accepted traditions of the origin of this sect.
Human Chromosome 17 in Essential Hypertension
Authors: Knight J. , Munroe P. B. , Pembroke J. C. , Caulfield M. J. 
Published: March 2003

SummaryHypertension affects up to 30% of the adult population in Western societies and is a major risk factor for kidney disease, stroke and coronary heart disease. It is a complex trait thought to be influenced by a number of genes and environmental factors, although the precise aetiology remains unknown at this time. A number of methods have been successfully used to identify mutations that cause Mendelian traits and these are now being applied to the investigation of complex diseases. This review summarises the data gathered, using such approaches, that suggest there is a gene or genes on chromosome 17 causing human essential hypertension. Studies in rodent models are discussed first, followed by studies of human hypertension that include the investigation of pseudohypoaldosteronism type II, a monogenic trait that manifests with hypertension alongside other phenotypic variables. In addition, candidate gene studies, genome screens and linkage studies based on comparative mapping are outlined. To date no gene has been identified on human chromosome 17 that influences blood pressure and causes human essential hypertension. However, results of ongoing fine mapping and candidate gene studies in both rodents and man are eagerly awaited.
Side effects of botanical insecticides on predatory mite Amblyseius andersoni (Chant)
Authors: Castagnoli M. , Angeli G. , Liguori M. , Forti D. , Simoni S. 
Published: March 2003

AbstractThe effects of the botanical insecticides Biopiren plus, Piresan plus and Neemazal T/S on the predatory mite Amblyseius andersoni (Chant) were tested under laboratory, semi‐field, and field conditions. The tests carried out in the laboratory allowed detection of the direct toxicity on eggs and females as well as the effects on fecundity, whereas semi‐field trials assessed their residual toxicity. In laboratory and semi‐field tests, pyrethrins, particularly Piresan plus, proved to have the highest toxicity with E value, concerning both female mortality and fecundity, of 100 % and 45 %, respectively. The same product tested in the field only caused a significant reduction in the phytoseiid population shortly after the treatment. The relevant escape rate registered in semi‐field tests could explain the lack of phytoseiid eradication in the field after treatment with pyrethrins.