58 research outputs found
LONG-TERM PROGNOSIS OF PATIENTS WITH CYSTIC-FIBROSIS IN RELATION TO EARLY DETECTION BY NEONATAL SCREENING AND TREATMENT IN A CYSTIC-FIBROSIS CENTER
No full textBackground - A study was undertaken to evaluate whether an early diagnosis by neonatal screening may improve the long term prognosis of patients with cystic fibrosis and to assess the influence of expert management started immediately after the diagnosis.Methods - Comparative clinical follow up in three birth cohorts of patients with cystic fibrosis was performed at the Cystic Fibrosis centre in Groningen in close collaboration with paediatricians in general hospitals in the north-eastern part of the Netherlands. The first birth cohort (n=19) was detected by screening and the two other cohorts were detected clinically, one (n=30) consisting of patients born during the screening programme and the other (n=32) of patients born during the six years immediately after the screening programme ended. The total number of patients in the three birth cohorts included all patients with cystic fibrosis born in this area during a 12 year period. Cumulative survival rates and the variation with time of lung function, the levels of immunoglobulins, and growth patterns were used as main outcome measures.Results - Patients born during the screening programme but detected clinically appeared to have a reduced life expectancy compared with patients detected by screening. The patients detected by screening showed less deterioration in lung function (annual decrease 1.2% of FEV, % pred), a smaller increase in immunoglobulin levels, and minimal catch-up growth compared with an annual decrease of 3.25% of FEV, % pred in the non-screened birth cohort of the same age, a higher rise in immunoglobulins leading to increased levels at the end of the observation period, and catch-up growth for weight as well as height. Differences between patients treated in a cystic fibrosis centre and those not referred to a specialist centre were smaller but similar, in favour of treatment at a cystic fibrosis clinic.Conclusions - Expert management started immediately after an early diagnosis of cystic fibrosis by neonatal screening results in important beneficial effects on the outcome and clinical course of the condition. The institution of very early treatment may be critical for the outcome and long term prognosis for most patients with cystic fibrosis. Neonatal screening programmes for cystic fibrosis should be introduced more widely.</p
Association and haplotype sharing due to identity by descent, with an application to genetic mapping
No full textLONG-TERM PROGNOSIS OF PATIENTS WITH CYSTIC-FIBROSIS IN RELATION TO EARLY DETECTION BY NEONATAL SCREENING AND TREATMENT IN A CYSTIC-FIBROSIS CENTER
No full textBackground - A study was undertaken to evaluate whether an early diagnosis by neonatal screening may improve the long term prognosis of patients with cystic fibrosis and to assess the influence of expert management started immediately after the diagnosis. Methods - Comparative clinical follow up in three birth cohorts of patients with cystic fibrosis was performed at the Cystic Fibrosis centre in Groningen in close collaboration with paediatricians in general hospitals in the north-eastern part of the Netherlands. The first birth cohort (n=19) was detected by screening and the two other cohorts were detected clinically, one (n=30) consisting of patients born during the screening programme and the other (n=32) of patients born during the six years immediately after the screening programme ended. The total number of patients in the three birth cohorts included all patients with cystic fibrosis born in this area during a 12 year period. Cumulative survival rates and the variation with time of lung function, the levels of immunoglobulins, and growth patterns were used as main outcome measures. Results - Patients born during the screening programme but detected clinically appeared to have a reduced life expectancy compared with patients detected by screening. The patients detected by screening showed less deterioration in lung function (annual decrease 1.2% of FEV, % pred), a smaller increase in immunoglobulin levels, and minimal catch-up growth compared with an annual decrease of 3.25% of FEV, % pred in the non-screened birth cohort of the same age, a higher rise in immunoglobulins leading to increased levels at the end of the observation period, and catch-up growth for weight as well as height. Differences between patients treated in a cystic fibrosis centre and those not referred to a specialist centre were smaller but similar, in favour of treatment at a cystic fibrosis clinic. Conclusions - Expert management started immediately after an early diagnosis of cystic fibrosis by neonatal screening results in important beneficial effects on the outcome and clinical course of the condition. The institution of very early treatment may be critical for the outcome and long term prognosis for most patients with cystic fibrosis. Neonatal screening programmes for cystic fibrosis should be introduced more widely
Association and haplotype sharing due to identity by descent, with an application to genetic mapping
No full textEfficiency control in large-scale genotyping using analysis of variance
No full textThe efficiency of the genotyping process is determined by many simultaneous factors. In actual genotyping, a production run is often preceded by small-scale experiments to find optimal conditions. We propose to use statistical analysis of production run data as well, to gain insight into factors important for the outcome of genotyping. As an example, we show that analysis of variance (ANOVA) applied to the first-pass results of a genetic study reveals important determinants of genotyping success. The largest factor limiting genotyping appeared to be interindividual variation among DNA samples, explaining 20% of the variance, and a smaller reaction volume, sizing failure, and differences among markers all explained similar to10%. Other potentially important factors, such as sample position within the plate and reusing electrophoresis matrix, appeared to be of minor influence. About 55% of the total variance could be explained by systematic factors. These results show that ANOVA can provide valuable feedback to improve genotyping efficiency. We propose to adjust genotype production runs using principles of experimental design in order to maximize genotyping efficiency at little additional cost.</p
Efficiency control in large-scale genotyping using analysis of variance
No full textThe efficiency of the genotyping process is determined by many simultaneous factors. In actual genotyping, a production run is often preceded by small-scale experiments to find optimal conditions. We propose to use statistical analysis of production run data as well, to gain insight into factors important for the outcome of genotyping. As an example, we show that analysis of variance (ANOVA) applied to the first-pass results of a genetic study reveals important determinants of genotyping success. The largest factor limiting genotyping appeared to be interindividual variation among DNA samples, explaining 20% of the variance, and a smaller reaction volume, sizing failure, and differences among markers all explained similar to10%. Other potentially important factors, such as sample position within the plate and reusing electrophoresis matrix, appeared to be of minor influence. About 55% of the total variance could be explained by systematic factors. These results show that ANOVA can provide valuable feedback to improve genotyping efficiency. We propose to adjust genotype production runs using principles of experimental design in order to maximize genotyping efficiency at little additional cost.</p
Haplotype sharing tests of linkage disequilibrium in a Hutterite asthma data set
No full textThe Genetic Analysis Workshop 12 genome scan data set for "strict" asthma in a Hutterite population was analyzed using haplotype sharing analysis (HSA), which tests for differences in mean length of haplotype sharing around each marker for pairs of chromosomes in cases versus controls. The regions of chromosome 1 and 8 where evidence for linkage was observed in published analyses were negative by HSA. HSA yielded positive results on chromosomes 7, 12, 16, 18, and 21 (p = 0.003 on 21q). Although there are reports of support for linkage to asthma in some of these regions, it is not known whether any represent true positives. Further study is needed of the possible role of length-based measures of linkage disequilibrium in recent population isolates. (C) 2001 Wiley-Liss, Inc.</p
Haplotype sharing tests of linkage disequilibrium in a Hutterite asthma data set
No full textThe Genetic Analysis Workshop 12 genome scan data set for "strict" asthma in a Hutterite population was analyzed using haplotype sharing analysis (HSA), which tests for differences in mean length of haplotype sharing around each marker for pairs of chromosomes in cases versus controls. The regions of chromosome 1 and 8 where evidence for linkage was observed in published analyses were negative by HSA. HSA yielded positive results on chromosomes 7, 12, 16, 18, and 21 (p = 0.003 on 21q). Although there are reports of support for linkage to asthma in some of these regions, it is not known whether any represent true positives. Further study is needed of the possible role of length-based measures of linkage disequilibrium in recent population isolates. (C) 2001 Wiley-Liss, Inc
The probability that similar haplotypes are identical by descent
No full textThe logic of gene mapping in highly penetrant diseases is to find the minimal overlap of haplotypes that are identical by descent (IBD). If the pedigree is unknown, identity by descent of haplotype overlap cannot be established with certainty. In many cases, it is intuitively clear that similar haplotypes are indeed IBD. The logical and statistical evaluation of haplotype overlap requires that probabilities of IBD are substantial. It is, therefore, important to estimate these probabilities. In this paper, we derive a recursive formula for the probability of IBD. Simulations are used to validate the expected values and to study the variability around the expected value. We demonstrate that for populations 1000 generations of age - without bottlenecks - haplotypes of 1 cM consisting of at least five microsatellite markers have a significant probability to be IBD. Likewise, SNP haplotypes of 1 cM should consist of at least nine identical SNP alleles for a similar probability of IBD. Without considering bottlenecks, haplotypes consisting of as few as three SNPs spanning a region of less than 0.01 cM are likely IBD in populations that are 10000 generations of age
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