bluuebunny/crossref_metadata_2025 huggingface dataset:
Resilience programs for children in disaster
Authors: Grotberg Edith Henderson
Published: March 2003

OBJECTIVES The long‐term objectives of the International Resilience Research Project (IRRP), were to indicate: a. how children become resilient and how service providers incorporate the promotion of resilience into their programs. The intermediary objectives were to: (1) indicate how resilience is promoted in different cultures with different age groups; (2) identify what resilience behaviors deal with and overcome the potentially damaging aspects of adversities and disasters; and (3) identify the role of adults in promoting resilience in their children and in themselves.

METHOD The data from the International Resilience Research Project were reanalysed in order to link the results to subsequent research and program development, including resilience programs for children in disaster. The methodology was based on purposeful samples of selected families with children in specific age groups (0–3; 4–6; 9–11 years). Each researcher, representing 27 sites in 22 countries, received the Methodology Guidance and Manual for the Training of Interviewers, designed and developed by an International Advisory Committee; a demographic sheet; a packet of the 15 constructed situations and forms with the questions to be answered; and additional standardized tests for validation. Data were returned to the project director for scoring, with reliability checks, and qualitative data analysis at Civitan International Research Center, University of Alabama, Birmingham.

RESULTS Parents and children at 27 sites in 22 countries, from Russia to Vietnam, from Namibia to Finland, from Chile to Canada, provided the data. A total of 1225 target children and their families participated, with 2204 responses from parents, and 1194 responses from children. The results of the data gathered from 1993 to 1997 were, briefly, these: (1) one‐third of the respondents exhibited resilience or its promotion; (2) by the age of 9 years, children can promote their own resilience at the same rate as adults; (3) socio‐economic status had an insignificant impact on resilience promotion and behavior; (4) boys and girls had the same frequency of resilience promotion and behavior, with girls relying more on interpersonal skills in dealing with adversities and boys relying more on pragmatic problem solving skills; and (5) cultural differences exist, but do not prevent the promotion of resilience.

CONCLUSION Resilience can be promoted, and programs for children in disaster are feasible. Such programs can be adapted to children, adults, service providers, students, and those working with children in disasters. The programs can be independent or incorporated as part of existing service programs. Further, such programs can be adapted to different cultures.

IMPLICATIONS FOR PRACTICE Professionals can incorporate the promotion of resilience into their service programs in regular or disaster settings. As a consequence, they can improve services and thereby the physical and mental health of children and families coping with disaster.
Increased health care utilization associated with child day care among health maintenance organization and Medicaid enrollees
Authors: Lu Ning , Samuels Michael E
Published: March 2003

Objective This study examined the association between child day care and the utilization of health care resources. It also investigated whether increased use of health care resources in day‐care children is due to acute diarrheal illness or upper respiratory tract infections (URI).

Sample Study subjects were recruited as day‐care children (n = 435) and home‐care children (n = 753) through a health maintenance organization (HMO) and a consortium of Medicaid providers in Columbia, South Carolina, and were followed bimonthly for 18 months.

Method A survey was conducted to collect data on children aged 5 years or younger from their parents. The questionnaires collected familial information, individual characteristics, disease‐related symptoms, and the information on physician visits, antibiotic use, and use of other medicines. The association between day care attendance and the likelihood of using health care resources was examined by multivariate logistic regression analyses.

Results Compared with home‐care children, the odds ratios for physician visits, use of antibiotics, and use of other medicines were all significantly greater for children attending day care. However, the increased likelihood of physician visits in day‐care children may not be attributable to diarrheal illness or URI.

Conclusions Day care attendance is associated with the increased use of health care. Antibiotics are more likely to be prescribed in day‐care children than in home‐care children for diarrheal illness and URI.

Implications for practice Understanding the association between child day care attendance and utilization of health care resources will assist health care providers in evaluating their practice in providing medical care to children.
Levels of Care: primary care residents' self‐assessment of ability to care for children with chronic health conditions
Authors: Burke Robert T , Kiessling Louise S
Published: March 2003

Objectives To investigate the use of Levels of Care model to measure the self‐assessed ability of physicians in training to care for children with chronic health conditions.

Design Questionnaire presenting 45 case scenarios of children with various chronic health conditions was given to 85 residents training in pediatrics (46) or family medicine (39). The resident estimated for each case scenario the Level of Care (LoC I–V) that the resident felt able to provide ‘now, while in training’, and would want to provide when entering ‘practice’.

Setting University‐based, postgraduate, primary care specialty training programs in pediatric and family medicine.

Participants A total of 85 resident physicians in postgraduate training programs in the primary care specialties of family medicine (FM) and pediatrics (Pd).

Results Thirty‐nine family medicine (100%) and 30 pediatric residents (65%) responded. Median Level of Care (LoC FM‐1) that the family medicine residents felt able to provide while in ‘training’ was III and for the pediatric residents (LoC Pd‐1) was IV, χ2 = 42.595, p = 0.0001. The median Level of Care residents wanted to be able to provide in ‘practice’ for each group was LoC‐IV, χ2 = 13.85, p = 0.0078. There were statistically significant differences in responses between family medicine (FM) and pediatric (Pd) residents to both the ‘training’ and ‘practice’ questions.

Conclusions A self‐assessment instrument incorporating the Levels of Care (LoC) concept was useful to assess the self‐perceived ability of resident physicians in training to care for children with chronic health conditions.
Support of universal newborn hearing screening among mothers and health care providers
Authors: Wall Terry C , Peralta‐Carcelen Myriam , Fargason Crayton A , Evans H Hughes , Snyder Erin Dunn , Woolley Audie L
Published: March 2003

Background Despite the 1994 Joint Committee on Infant Hearing recommendation that all newborns receive hearing screens, many in the United States are not screened by 3 months of age.

Objectives To assess mothers’, pediatricians’, and hearing specialists’ preferences for targeted versus universal newborn hearing screening.

Study design An interactive computer‐based interview, applying the analytical hierarchical process, was used to quantify preference scores for 95 post‐partum women selected randomly from an obstetric ward at a university hospital and for 40 primary care pediatricians and 40 hearing specialists (audiologists and otolaryngologists) randomly selected from a local community. The main outcome of interest was preference for targeted versus universal newborn hearing screening. Three objectives were compared minimize missed hearing loss, minimize unnecessary tests, and minimize cost. Unnecessary tests included consideration of test time, test accuracy, and need for follow‐up hearing evaluations.

Results The majority of respondents in all three groups (97.5% hearing specialists, 82.5% pediatricians, and 89.5% mothers) favored universal over targeted screening. Differences in mean preference scores were statistically significant between hearing specialists and pediatricians (p < 0.005) and between hearing specialists and mothers (p < 0.005). All three groups ranked risk of missed hearing impairment as the most important consideration. Hearing specialists placed more weight on importance of not missing a case of hearing loss and less on unnecessary tests than mothers and pediatricians.

Conclusions Even though universal newborn hearing screening was preferred by the three groups examined, a small but significant minority of pediatricians and mothers preferred targeted screening.
Asthma, wheeze and cough in 7‐ to 9‐year‐old British schoolchildren
Authors: Coleman Helen , McCann Donna C , McWhirter Jenny , Calvert Marguerite , Warner John O
Published: March 2003

Background Report on the characteristics of a cohort of children, aged 7–9 years, attending schools in the south of England and participating in a controlled intervention study to improve the care and knowledge of asthma in junior and primary schools and highlight problems for potential intervention.

Methods A survey employing the International Study of Asthma and Allergies in Childhood (ISAAC) asthma questionnaire was undertaken to record the prevalence of asthma and the characteristics of children with asthma and wheeze in Year 3 and 4 pupils (age 7–9 years) in 25 schools, and to define disease severity and its management.

Results Responses on 1732 children were received. Reports of asthma and wheeze in this study were similar to those in recent ISAAC studies. The frequency and severity of symptoms was associated with appropriate therapeutic intervention suggesting adherence to published British Thoracic Society (BTS) guidelines. However, 80% of children with asthma at any BTS level of treatment reported exercise‐induced wheeze, indicating a need for education on pre‐exercise inhaler use. One in 20 children who had wheezed in the past 12 months reported a symptom profile suggestive of unrecognised asthma. Significant associations were found between maternal smoking and both wheeze in the last 12 months [odds ratio (OR), 1.35; confidence interval (CI): 1.01–1.81, p < 0.05] and nocturnal cough [OR, 1.70; CI: 1.31–2.20, p < 0.001].

Conclusions The characteristics of this sample are similar to those found for children of a similar age group in other studies. Therapeutic intervention is appropriate for the severity of disease but there are high levels of exercise‐induced wheeze despite adequate control of other symptoms. Five percent of children who reported wheezing in the previous 12 months had a symptom profile of untreated asthma. Maternal cigarette smoking was associated with wheeze and cough.

Implications for practic Recurrent untreated wheeze remains a problem for 5% of children reporting wheeze. A therapeutic hole has been identified – there is a need for further education on pre exercise inhaler use. Both these problems could be addressed by a school‐based asthma management strategy. Maternal smoking and its effects on childhood asthma and wheeze need to be addressed.
The greatest impact of war and conflict
Authors: Mandalakas Anna Maria
Published: March 2003

OBJECTIVE To review the available literature, explore developmental vulnerability, and highlight long‐term outcomes found in children exposed to complex humanitarian emergencies (CHEs).

DESIGN Literature review.

RESULTS Children involved in CHEs are at risk for a number of poor long‐term outcomes. Children exposed to malnutrition during the first two trimesters and early in life are at risk for poor cognitive, behavioral and psychological function. The existing literature consistently describes the high incidence of psychological trauma experienced by children involved in CHEs. There is limited research examining the long‐term outcomes and/or effectiveness of interventions applied in these children.

CONCLUSIONS These insults affect children's subsequent development and diminish their ability to function successfully as adults. Communities suffer from these insults for decades as these children become the adults challenged with rebuilding their societies and avoiding future conflict.

IMPLICATIONS FOR PRACTICE Recognition of children's vulnerability, advocacy on the part of child health professionals and inclusion of appropriately trained child health specialists on emergency response teams are critical to minimizing children's risk of poor long‐term outcome. It is important to recognize the great amount of variability in children's resiliency and coping abilities. This variability is determined by a number of factors that are both fixed and modifiable. There are several broad, conceptual approaches that child health professional can employ to modify these factors, empower children and optimize long‐term outcome. Future research designed to examine these issues is greatly needed.
Cytogenetic and molecular investigations of Y chromosome sequences and their role in Turner syndrome
Authors: QUILTER C. R. , TAYLOR K. , CONWAY G. S. , NATHWANI N. , DELHANTY J. D. A.
Published: March 2003

It has been proposed that all live born females with Turner syndrome carry a cell line containing two sex chromosomes, which may be present at a low level of mosaicism (Hook & Warburton, 1983; Hassold et al. 1985; 1988; Connor & Loughlin, 1989). If the second sex chromosome is a Y, these patients are at risk of developing gonadoblastoma. In this study, 50 patients found to have a 45,X karyotype by conventional cytogenetic analysis, were screened by the polymerase chain reaction (PCR), for the presence of Y chromosome sequences. Two patients were positive for six of the eight Y chromosome loci tested and additional cytogenetic analysis confirmed the presence of a marker chromosome, in 8% and 3% of cells respectively. Fluorescence in situ hybridization (FISH) was used to confirm that the markers were of Y chromosome origin and helped to elucidate their structure. In addition, four other patients were found to have a Y chromosome by initial routine cytogenetic analysis. FISH, in conjunction with PCR, elucidated the structure of the Y chromosomes. This study illustrates the value of using a combination of cytogenetic and molecular techniques, to identify Y chromosome sequences in Turner syndrome.
A splicing mutation of the RHAG gene associated with the Rhnull phenotype
Authors: KAWANO M. , IWAMOTO S. , OKUDA H. , FUKUDA S. , HASEGAWA N. , KAJII E.
Published: March 2003

Rhnull is a syndrome serologically characterized by the deficiency of all Rh antigens on human red blood cells. Rhnull is divided into two types: regulator and amorph. Recently, Cherif‐Zahar et al. proposed that the RHAG gene encoding the Rh50 glycoprotein is a candidate for inducing regulator type Rhnull. We investigated both the RH and RHAG genes in an Rhnull individual. The reticulocytes from the propositus had RHD, RHcE, and RHCe transcripts without any mutation. However, the sequence analysis of RHAG cDNA showed a deletion of 122 bp from nucleotide 946 to 1067. This deletion was revealed to be due to a homozygous splicing mutation, which is a single base substitution at the consensus sequence of the splicing acceptor site (AG→AT). The mutation appeared to break the ‘GT‐AG’ splicing rule and to cause 122 bp exon skipping accompanied by a frameshift. This study confirms that the RHAG gene is the most likely candidate for the ‘regulator’ gene of Rhnull cases.
HLA evidence for the lack of genetic heterogeneity in Basques
Authors: COMAS D. , CALAFELL F. , MATEU E. , PÉREZ‐LEZAUN A. , BERTRANPETIT J.
Published: March 2003

To examine the possible internal heterogeneity within the Basque population, nine samples typed for several HLA loci were compiled and HLA‐A, B, C and DR loci were analysed. First, the shared features of HLA in Basques were analysed by principal component analysis and genetic distances. Two major Basque dialect groups (‘French’ and ‘Spanish’) were considered. FST statistics were computed and corrected for sampling intensity. The dialectal and political division did not seem to differentiate these two groups genetically. Analysis of Molecular Variance also failed to show consistently significant genetic variance components between French and Spanish Basques. Thus, in this particular example, linguistic diversity does not seem to correlate with a genetic stratification.
Phenylketonuria – a problem in eugenics
Authors: PENROSE L. S.
Published: March 2003

Inaugural Lecture delivered at University College on 21 Jan. 1946 and reprinted with permission from The Lancet, 29 June 1946, pp. 949–953

For academic purposes, eugenics is defined as the study of agencies under social control that may improve or impair the racial qualities of future generations either physically or mentally. This formula allows many different interpretations. The subject matter might involve almost any material studied in medicine, psychology or social science. In the light of knowledge of its frequent misuse, inclusion of the term “racial” in the definition seems unfortunate. A racial quality is presumably any character which differs in frequency or which (when it is metrical) differs in average value in two or more large groups of people. No qualities have been found to occur in every member of one race and in no member of another. Furthermore, as Morant (1939) has shown in his analysis of European populations, differences between average measurements in the so‐called races are often much smaller than commonly supposed. The qualities by which people differ can be treated as legitimate material for scientific investigation without employing any invidious concept of race. The human race constitutes the field of eugenic inquiry.

A popular view of eugenics, which has in the past been encouraged by propaganda groups such as eugenic societies and human betterment foundations, implies active interference in human reproduction. The general grounds for interference are often held to be that civilisation has tended to reverse the process of natural selection because the weaklings are now being fostered at the expense of the naturally strong. Not only are the physically and mentally inferior prevented from perishing in infancy by the activities of medical and social services but also, when the weaklings grow up, they are supposed to be more fertile than the normal. As Karl Pearson (1909) once put it, “we have suspended the racial purgation maintained in the less developed communities by natural selection.” Degeneration of the physical and mental level of civilised peoples is believed to be inevitable unless eugenic measures are taken to counteract it.
Identification of a mutation (A1879G) of transferrin from cDNA prepared from peripheral blood cells
Authors: PANG H. , KODA Y. , SOEJIMA M. , KIMURA H.
Published: March 2003

We have prepared a transferrin (TF) cDNA from total RNA of peripheral blood cells of an individual with a TF B variant (TF Bv) phenotype to analyze the molecular basis for the TF Bv. The TF B variant allele (TF Bv) was found to contain an A to G transition at nucleotide 1879 in the coding region that may result in substitution of glutamic acid for lysine at codon 627 located in exon 16. In addition, a transient expression study by transfection of each plasmid containing TF C1, TF C2 or TF Bv cDNA into monkey kidney (COS7) cells indicated that the products from specific TF alleles were able to be identified respective phenotypes by isoelectrofocusing electrophoresis and immunoblotting analyses. Based on this nucleotide substitution, we also established a PCR–RFLP method to detect the TF Bv allele from genomic DNA. Thus, peripheral blood cells were useful as an alternative source for preparation of cDNA from human liver for the molecular analysis of TF polymorphism.
A PDZ domain‐containing protein with homology to Diphor‐1 maps to human chromosome 1q21
Authors: WHITE K. E. , BIBER J. , MURER H. , ECONS M. J.
Published: March 2003

The novel gene, Diphor‐1, was recently cloned from rat kidney and shown to increase phosphate uptake in cells when co‐expressed with a Na+‐Pi cotransporter, indicating that it may play a substantial role in cellular phosphate balance. Previously, the phosphate wasting disorder, autosomal dominant hypophosphatemic rickets (ADHR) was mapped to chromosome 12p13 by linkage analysis. In the present work, PDZK1, a PDZ domain‐containing protein highly homologous to rat Diphor‐1, was shown to be expressed in human kidney. Based upon its sequence similarity to rat Diphor‐1, we considered PDZK1 a feasible candidate gene for ADHR. PDZK1 was found to localize to human chromosome 1q21, thereby ruling it out as a candidate for ADHR.
Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16
Authors: CAVANAUGH J. A. , CALLEN D. F. , WILSON S. R. , STANFORD P. M. , SRAML M. E. , GORSKA M. , CRAWFORD J. , WHITMORE S. A. , SHLEGEL C. , FOOTE S. , KOHONEN‐CORISH M. , PAVLI P.
Published: March 2003

A number of localizations for the putative susceptibility gene(s) have been identified for both Crohn's disease and ulcerative colitis. In a genome wide scan, Hugot et al. (1996) identified a region on chromosome 16 which appeared to be responsible for the inheritance of inflammatory bowel disease in a small proportion of families. Subsequent work has suggested that this localization is important for susceptibility to Crohn's disease rather than ulcerative colitis (Ohmen et al. 1996; Parkes et al. 1996). We investigated the contribution of this localization to the inheritance of inflammatory bowel disease in 54 multiplex Australian families, and confirmed its importance in a significant proportion of Crohn's disease families; we further refined the localization to a region near to D16S409, obtaining a maximum LOD score of 6.3 between D16S409 and D16S753.
Structure and organization of the human deoxyribonuclease II (DNase II) gene
Authors: YASUDA T. , TAKESHITA H. , IIDA R. , TSUTSUMI S. , NAKAJIMA T. , HOSOMI O. , NAKASHIMA Y. , MORI S. , KISHI K.
Published: March 2003

The structure of the human gene for deoxyribonuclease II (DNase II; EC 3.1.22.1) was determined using several specific primers based on the human DNase II cDNA sequence [Yasuda et al. (1998). J. Biol. Chem.273, 2610–2616] in a polymerase chain reaction‐based strategy. The gene spanned about 6 kb and consisted of 6 exons. No canonical TATA or CAAT boxes could be identified within the 1341 nucleotides upstream of the putative transcription start site, although the 5′‐flanking region contained a CpG island and several putative binding motifs for transcription factors Sp1 and ETF. These properties indicate that the DNase II gene is a housekeeping gene and this is compatible with its ubiquitous expression in human tissues. Three different cleavage/polyadenylation sites were identified in the 3′‐flanking region, leading to the production of multiple DNase II mRNA species. However, a comparison of the entire translated sequences of the gene from a pair of subjects with homozygous DNase II phenotypes H and L revealed no differences in the nucleotide sequences.
Semiparametric linkage analysis using pseudolikelihoods on neighbouring sets
Authors: LI H. , HUANG J.
Published: March 2003

For many complex diseases, study has suggested that the disease genes influence not only the occurrence of the disease, but also the age of onset. Current methods in linkage analysis are mainly concentrated on affected relative pairs or affected family members, and age of onset information is either ignored or is taken into account by specifying age‐dependent penetrances for liability classes. In fact, affected relatives with different ages of onset may be the result of different genetic aetiologies and unaffected relatives are censored at the study time. Therefore, incorporation of age of onset and including contrasts between affected and unaffected pedigree members are important components of effective analysis for the detection of linkage with genetic markers. We use multiple markers to infer the inheritance vector in order to extract information about the inheritance pattern of the disease allele in a pedigree. For a given inheritance vector, we define two neighbour sets for each individual based on allele identical by descent (IBD). We then use the within‐set and between‐sets conditional hazard ratios to characterize the dependence of age of onset among relatives. A pseudolikelihood ratio test is proposed for testing linkage. Simulated and real data sets are used to illustrate these new statistical methods.
TDT statistics for mapping quantitative trait loci
Authors: XIONG M. M. , KRUSHKAL J. , BOERWINKLE E.
Published: March 2003

The original transmission disequilibrium test (TDT), was introduced to test for linkage between a marker and a disease‐susceptibility locus (Spielman et al. 1993). Allison (1997) extended the TDT procedure to quantitative traits. Allison's test, however, is restrictive in that it requires family trios consisting of one heterozygous parent, one homozygous parent and one child, and considers only the situation where the marker locus is analogous to the quantitative trait locus itself. In this paper, we propose, investigate and apply a general TDT for quantitative traits that permits more than one child per family, does not require only one parent to be heterozygous, and allows for the fact that the various alleles at the marker and trait loci may be at varying degree of linkage disequilibrium. We also show that this TDT for quantitative traits is still a valid test of linkage in the presence of population substructure. To provide guidelines for study design, we develop analytic formulae for calculation of the power of the TDT for mapping quantitative trait loci and investigate the impact of various factors on the power. Power calculations show that the proposed TDT for quantitative traits is more powerful than Allison's basic test statistic and the extreme discordant sib pair linkage method. The proposed TDT statistic for quantitative traits is applied to systolic blood pressure variation in the Rochester Family Heart Study using an extremely discordant sibling pair design.
Human aneuploidy: lessons from achiasmate segregation in Drosophila melanogaster
Authors: KOEHLER K. E. , HASSOLD T. J.
Published: March 2003

Aneuploidy is a crucial issue in human reproductive biology, accounting for both a significant proportion of miscarriages and, among liveborns, multiple congenital malformation syndromes such as Down Syndrome. Although the etiology of human aneuploidy remains poorly understood, recent studies have elucidated certain fundamental correlates of meiotic nondisjunction, such as altered recombination. These features are extraordinarily similar to those associated with chromosome misbehavior in Drosophila melanogaster females. Furthermore, these organisms also share a significant level of achiasmate chromosome nondisjunction. Here we describe in detail the processes of achiasmate chromosome segregation in Drosophila and discuss how they may be most effectively applied to our understanding of the etiology of human aneuploidy. In particular, we examine the possibility that similar “backup” mechanisms of chromosome segregation might function in mammalian meiosis, particularly mammalian females. Drawing upon observations made in flies, we also propose a new model for the segregation of achiasmate chromosomes in humans.
Comprehensive mutation analysis of TSC1 using two‐dimensional DNA electrophoresis with DGGE
Authors: DABORA S. L. , SIGALAS I. , HALL F. , ENG C. , VIJG J. , KWIATKOWSKI D. J.
Published: March 2003

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of benign tumors in multiple organs often causing serious neurologic impairment. To develop a reliable genetic test for TSC, two‐dimensional electrophoresis with denaturing gradient gel electrophoresis (2D DGGE) has been developed to detect mutations in TSC1. The 23 exons of TSC1were amplified using two rounds of PCR. In the first round, all coding regions of TSC1 were amplified in four fragments ranging in size from 7.4 kb to 9.9 kb. In the second round, 32 fragments representing 23 exons were amplified using primers designed to avoid overlapping fragments and with a GC clamp on one end to optimise melting characteristics. These exon fragments were then separated by size in the first dimension using a polyacrylamide gel, and by melting characteristics in the second dimension using a urea/formamide gradient to yield 32 distinct bands. If a mutation is present, four bands instead of one, are typically observed. During the development of this assay, we analysed 63 patient samples with known TSC1 mutations from prior studies. These 63 patients had 68 known mutations or polymorphisms. With DGGE, all 68 of these were identified (45 point mutations, 3 small insertions, 20 small deletions) and an additional 27 single base variants were discovered. To evaluate the assay, we analysed 19 of these samples in a blinded study. In the blinded analysis, 19/20 (95%) known mutations or polymorphisms were detected. The single missed mutation in the blinded analysis could be identified in retrospect and the assay was modified accordingly. During this study, we identified 2 new mutations (exon 8 and exon 15), a new polymorphism (intron 4), and the first variant identified in a non‐coding exon (exon 2).
Detailed haplotype analysis in Ashkenazi Jewish and non‐Jewish British dystonic patients carrying the GAG deletion in the DYT1 gene: evidence for a limited number of founder mutations
Authors: VALENTE E. M. , POVEY S. , WARNER T. T. , WOOD N. W. , DAVIS M. B.
Published: March 2003

The DYT1 gene on human chromosome 9q34 appears to be responsible for most cases of early onset primary torsion dystonia (PTD) both in Ashkenazi Jewish (AJ) and in non‐Jewish patients. Previous haplotype analysis in a 2 cM region surrounding the DYT1 gene showed that a single founder mutation (DYT1AJ) was responsible for most cases of early onset PTD in the North American AJ population and refined the most likely location of the gene to a 150 kb interval between the marker loci D9S2161 and D9S63.

Recently, the majority of cases of early onset PTD in both AJ and non‐Jewish patients were found to carry a unique 3‐bp (GAG) deletion in the coding region of the DYT1 gene. This deletion appears to have arisen more than once, suggesting independent mutational events.

In this study, we analysed the haplotypes surrounding DYT1 in 9 AJ and 15 non‐Jewish British patients carrying the GAG deletion in the DYT1 gene. We found that all AJ British patients carried the same haplotype as the North American Jews, sustaining the theory that the current British AJ community descends from the same small group of individuals as the North American Jewry. Furthermore, in the non‐Jewish British patients, only a limited number of distinct founder mutations was observed. This supports the hypothesis that the GAG deletion in the DYT1 gene is not a very frequent mutation, and that it has arisen only a limited number of times throughout the centuries.
Locus and population specific evolution in HLA class II genes
Authors: VALDES A. M. , McWEENEY S. K. , MEYER D. , NELSON M. P. , THOMSON G.
Published: March 2003

The population genetics of the HLA class II loci was studied with reference to variation in the frequency of (a) alleles at a locus and (b) amino acids at specific sites. Variation was surveyed at 4 loci (DRB1, DQA1, DQB1, and DPB1) in 22 populations from the Twelfth International Histocompatibility Workshop (Saint‐Malo, 1996). Allele and amino acid variation was measured by computing heterozygosity and the effective number of alleles. Substantial variations in polymorphism were observed among the various populations and loci studied. In the majority of the populations, DRB1 has the highest heterozygosity and effective number of alleles. As previously shown, the Amerindian populations have lower levels of allelic diversity when compared to other populations. At the amino acid level, DRB1 antigen recognition sites (ARS) have the highest heterozygosities and effective number of alleles. For the other loci (DPB1, DQA1, and DQB1) for which there is no crystal structure and for which ARS sites were inferred from DRB1, non‐ARS sites were often among the sites with highest levels of variation. It is possible that these putative non‐ARS sites do play a role in antigen presentation.

The homozygosity test for neutrality was applied to allele and amino acid data. Of the four HLA class II loci studied, only DPB1 failed to show evidence of balancing selection. DQB1 and DQA1 depart significantly from neutrality in the largest number of populations. Genetic distances between populations were computed based on frequency of alleles and amino acids at ARS sites.
Evolution of the apolipoprotein B gene and coronary artery disease: a study in low and high risk Asians
Authors: HENG C. K. , SAHA N. , LOW P. S.
Published: March 2003

This study traces the evolutionary pathways of the apolipoprotein B gene in the low risk Chinese and high risk Asian Indians in relation to coronary artery disease (CAD). Haplotypes were constructed from six apoB polymorphisms sp24/27, Ag(c/g), Ag(a1/d), XbaI, Ag(h/i) and, Ag(t/z). These were genotyped from 474 Chinese (253 healthy, 221 CAD patients) and 248 Asian Indians (164 healthy, 84 CAD patients). The maximum parsimony method was used to construct a cladogram for each ethnic group. Three haplotypes in the Chinese and one in the Indians were found exclusively in CAD patients. These haplotypes were sp27ca1X‐ht, sp24ga1X‐iz and sp24ca1X+it in Chinese, and sp24cdX‐it in Indians. Those in the Chinese all occurred as terminal haplotypes and represented the most recent mutations. Evolutionary pathways for both ethnic groups were similar for majority of the haplotypes except for the presence of an additional third branch in the Indians arising from the ancestral haplotype. However, this third branch does not appear to contribute to the susceptibility of the Indians to CAD.
An Asian–Native American paternal lineage identified by RPS4Y resequencing and by microsatellite haplotyping
Authors: BERGEN A. W. , WANG C.‐Y. , TSAI J. , JEFFERSON K. , DEY C. , SMITH K. D. , PARK S.‐C. , TSAI S.‐J. , GOLDMAN D.
Published: March 2003

Human paternal population history was studied in 9 populations [three Native American, three Asian, two Caucasian and one African‐derived sample(s)] using sequence and short tandem repeat haplotype diversity within the non‐pseudoautosegmal region of the Y chromosome. Complete coding and additional flanking sequences (949 base pairs) of the RPS4Y locus were determined in 59 individuals from three of the populations, revealing a nucleotide diversity of 0.0147%, consistent with previous estimates from Y chromosome resequencing studies. One RPS4Y sequence variant, 711C>T, was polymorphic in Asian and Native American populations, but not in African and Caucasian population samples. The RPS4Y 711C>T variant, a second unique sequence variant at DYS287 and nine Y chromosome short tandem repeat (YSTR) loci were used to analyze the evolution of Y chromosome lineages. Three unambiguous lineages were defined in Asian, Native American and Jamaican populations using sequence variants at RPS4Y and DYS287. These lineages were independently supported by the haplotypes defined solely by YSTR alleles, demonstrating the haplotypes constructed from YSTRs can evaluate population diversity, admixture and phylogeny.
REPORT on the Sixth International Workshop on Chromosome 9 held at Denver, Colorado, U.S.A., 27 October 1998
Authors: CHADWICK B. P. , CAMPBELL L. J. , JACKSON C. L. , OZELIUS L. , SLAUGENHAUPT S. A. , STEPHENSON D. A. , EDWARDS J. H. , WIEST J. , POVEY S.
Published: March 2003

A meeting on chromosome 9 was held on Tuesday, 27 October 1998 in Denver, with 38 participants (see appendix). Since the last meeting several of the positional cloning efforts on chromosome 9q have come to fruition, and the most detailed discussion was on 9p. Dr Ian Dunham from the Sanger Centre explained the strategy to be used for sequencing chromosome 9, and encouraged collaboration in the preparatory mapping. He indicated that some priority could be given to those regions where people in the field had a strong interest and could identify relevant PAC clones.

At this short meeting it was clearly not possible to construct a comprehensive map of chromosome 9, and it was decided that efforts should be made to maintain links to sources of information on the chromosome 9 web page (http://www.gene.ucl.ac.uk/chr9/). The discussions at the meeting are summarized in four sections: 9p, 9cen–q31, 9q32–9q34 and comparative mapping.

Many of the posters presented at the meeting were also presented at the ASHG meeting (28–31 October 1998). They are listed here and are published in The American Journal of Human Genetics, vol. 63 (supplement). Abstracts for posters presented only at this meeting are appended to this report.
Enzymatic characterization of four new mutations in the glucose‐6 phosphatase (G6PC) gene which cause glycogen storage disease type 1a
Authors: BRUNI N. , RAJAS F. , MONTANO S. , CHEVALIER‐PORST F. , MAIRE I. , MITHIEUX G.
Published: March 2003

Glycogen storage disease type 1a (GSD1a) is caused by mutations in the gene of glucose‐6 phosphatase (G6PC), encoding the last enzyme of gluconeogenesis and glycogenolysis. To study the effect of mutations previously identified, but not yet enzymatically characterized, in French GSD1a patients, we used an in vitro expression system of the human glucose‐6 phosphatase (hGlc6Pase) cDNA. Wild type hGlc6Pase expressed in COS‐7 cells exhibited kinetic features comparable to microsomal Glc6Pase from normal human liver and kidney. Four new mutations inducing aminoacid changes in the coding sequence, e.g. W77R, A124T, G184E and L211P, were inserted into the Glc6Pase cDNA by site‐directed mutagenesis, and studied after transient expression in COS‐7 cells. All four mutations totally abolished Glc6Pase activity.
Supportive evidence for contribution of the dopamine D2 receptor gene to heritability of stature: linkage and association studies
Authors: ARINAMI T. , IIJIMA Y. , YAMAKAWA‐KOBAYASHI K. , ISHIGURO H. , OHTSUKI T. , YANAGI H. , SHIMAKURA Y. , ISHIKAWA H. , HAMAGUCHI H.
Published: March 2003

Increases in height were reported in children chronically exposed prenatally and postnatally to D2 receptor‐blocking drugs. A possible haplotypic association between stature and the DRD2 gene was also reported. In this study, we examined linkage between stature and DRD2 by genotyping a dinucleotide repeat polymorphism in 79 sib‐pairs aged 8–17 years. An association between stature and a putative functional polymorphism in the promoter region of the DRD2 gene was examined in the sib‐pairs and in 125 unrelated male adults. All the subjects were Japanese. Linkage (p= 0.004, SIBPAL) and an association (p= 0.009, paired t‐test, in the sib‐pairs; p= 0.006, ANOVA, in the adults) with stature were suggested. These findings indicate that DRD2 is one of the genes that contribute to heritability of stature.
Y‐chromosome specific YCAII, DYS19 and YAP polymorphisms in human populations: a comparative study
Authors: QUINTANA‐MURCI L. , SEMINO O. , POLONI E. S. , LIU A. , VAN GIJN M. , PASSARINO G. , BREGA A. , NASIDZE I. S. , MACCIONI L. , COSSU G. , AL‐ZAHERY N. , KIDD J. R. , KIDD K. K. , SANTACHIARA‐BENERECETTI A. S.
Published: March 2003

Two hypervariable Y‐specific markers, the YCAII and DYS19 STRs, and the more stable Y Alu Polymorphism (YAP) have been analysed in about 1400 individuals of 21 different populations, mainly from Europe but also from the Middle East, Africa and Asia. On the basis of the frequency distributions of these three Y‐markers we compare, using different statistical analyses, their power in detecting population genetic structure and in distinguishing closely related groups. The pattern of populations' genetic affinities inferred from the three markers considered altogether suggests a strong genetic structure that, with a few exceptions, broadly corresponds to the linguistic relatedness and/or geographic location of the sampled populations.
Assessing linkage disequilibrium in a complex genetic system. I. Overall deviation from random association
Authors: ZHAO H. , PAKSTIS A. J. , KIDD J. R. , KIDD K. K.
Published: March 2003

Linkage disequilibrium is an important tool both at the end stages of positional cloning studies to map genes of particular interest and in reconstruction of population histories. With advances in molecular biology, complex genetic systems involving multiple highly polymorphic markers are becoming more commonly used to study linkage disequilibrium. These systems contain much more genetic information than simple two marker systems. In this article, we introduce a measure to summarize the overall deviation from random association and propose a permutation‐based estimate for this measure. The performance of the proposed estimation procedure is studied through simulations. The methods proposed in this paper are then applied to population data at the dopamine D2 receptor locus (DRD2) and at the homeobox B (HOXB) gene cluster.
The human dendritic cell marker CD83 maps to chromosome 6p23
Authors: BERCHTOLD S. , JONES T. , MÜHL‐ZÜRBES P. , SHEER D. , SCHULER G. , STEINKASSERER A.
Published: March 2003

The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a radiation hybrid mapping panel and FISH analysis on human metaphase chromosomes. PCR‐based analysis of a single chromosome hybrid panel identified the presence of the CD83 gene on human chromosome 6 and subsequent analysis of the Genebridge4 radiation panel located the gene between AFMa192wg9 and AFMb322wd1 with a lod score of 9.2. Finally, using FISH analysis the CD83 gene was localized to chromosome 6 band p23.
MUC1 gene polymorphism does not explain the different incidence of gastric cancer in Portugal and Denmark
Authors: CARVALHO F. , PEIXOTO A. , STEFFENSEN R. , AMORIM A. , DAVID L. , SOBRINHO‐SIMÕES M.
Published: March 2003

MUC1 is a highly polymorphic mucin type glycoprotein expressed on the surface of many epithelia, including gastric mucosa, and is present in several body fluids and mucous secretions. A genetic polymorphism due to variation in length of a 60 bp tandemly repeated sequence domain constitutes more than half of the coding region of the glycoprotein. We demonstrated previously in a Portuguese population sample that the frequency of small MUC1 alleles is increased in patients with gastric carcinoma, suggesting that the possession of small MUC1 alleles confers increased risk for gastric carcinoma development. This finding raised the possibility that the very high prevalence of gastric carcinoma in Portugal could be partly due to a high frequency of small MUC1 alleles in the Portuguese population. In the present study we compared the MUC1 allele distribution in a population of Danish blood donors with the distribution in a population of Portuguese blood donors. The frequency of small MUC1 alleles was significantly higher in the Danish than in the Portuguese sample, thus failing to lend support to the hypothesis that a relatively higher frequency of the small MUC1 alleles might account for the high prevalence of gastric carcinoma in Portugal when compared to Denmark.
Rapid and simple determination of hereditary haemochromatosis mutations by multiplex PCR–SSCP: detection of a new polymorphic mutation
Authors: SIMONSEN K. , DISSING J. , RUDBECK L. , SCHWARTZ M.
Published: March 2003

Hereditary haemochromatosis is a common inherited disorder leading to excessive accumulation of iron in various organs. Two missense substitutions at the HFE‐gene have recently been associated with the disease, 187C G and 845G → A (mutations H63D and C282Y, respectively). We present a simple, rapid PCR–SSCP multiplex screening method allowing the simultaneous detection of both substitutions. Furthermore, testing the method on 420 Danish blood donors revealed the presence of a hitherto undetected third substitution in 13 individuals. The new substitution, a 193A → T transversion, affects codon 65 changing the code for serine to that of cysteine (S65C). It may thus have functional consequences for the HLA class protein encoded by the HFE‐gene. The allele frequencies observed were: H63D 14.8%, C282Y 6.2% and S65C 1.5%, which for the two former alleles are in agreement with frequencies reported for other North European population samples.
Mosaic Turner syndrome: cytogenetics versus FISH
Authors: ABULHASAN S. J. , TAYEL S. M. , AL‐AWADI S. A.
Published: March 2003

Twenty‐two cases with Turner syndrome features were subjected to standard cytogenetic techniques using giemsa trypsin (GTG‐) banding then fluorescence in situ hybridization (FISH) using a specific whole‐X chromosome painting probe, Quint‐Essential Y‐specific DNA probe (AMELY) for Yp11.2, alpha‐satellite (DYZ3) probe and X/Y cocktail‐alpha satellite probe (ONCOR) for confirmation of the initial diagnosis and comparison of the two techniques. Eight cases (36%) showed the same karyotype results by both techniques [5 cases: 45,X/46,XX, 2 cases: 45,X/46,X,i(Xq) and one case with a triple cell line 45,X/46,XX/47,XXX]. In the other 14 cases (64%) the FISH technique has identified a third cell line in 7 cases (32%), delineated the origin of the marker in 5 cases (23%) to be derivative X and clarified the deletion of the Yp11.2 region in 2 cases (9%) with the 45,X/46,XY karyotype. The application of FISH has highlighted the differences between the initial diagnosis based on the standard cytogenetic technique and the final diagnosis determined by the application of DNA probes specific for the X and Y chromosomes. FISH proved useful in detection of the low frequency cell lines which need analysis of a large number of metaphase spreads by GTG‐banding, helped in identifying the nature and the origin of the unknown markers which has an important implication in the development of gonadal tumours and delineated the deletion of the Yp11.2 region in the 45,X/46,XY Turner patients.
Linkage disequilibrium between intra‐locus variants in the aminopeptidase n gene and test of their association with coeliac disease
Authors: GIORDANO M. , BOLOGNESI E. , D'ALFONSO S. , LESSI M. , ZAVATTARI P. , ODERDA G. , CLOT F. , PERCOPO S. , CASARI G. , GRECO L. , TOSI R. , MOMIGLIANO‐RICHIARDI P.
Published: March 2003

Coeliac disease (CD) is a multigenic and multifactorial enteropathy triggered by gluten‐composing proteins. A possible involvement of the intestinal Aminopeptidase N (APN) was investigated by an association analysis. SSCP analysis detected four variants at position 281, 378, 956 and 2957 (referred to no. g178535, GenBank) that were studied in 193 Italian CD families. The haplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D′= D/Dmax) between the polymorphic sites were calculated. Significant D′ values ranged between 0.78 and 0.31. Association with CD was tested by TDT (Transmission Disequilibrium Test) utilizing as markers the nucleotide substitutions and their haplotypic combinations. No statistically significant transmission distortion to the probands or to their clinically silent sibs was observed. Our data exclude an involvement in CD of the tested markers and of further undetected variation in strong linkage disequilibrium (D′≅ 1) with them. The power of the test was not adequate to detect an association with an unknown polymorphism which is not in complete linkage disequilibrium with those analysed.