Papers by Gerard J te Meerman
Parallel genome analysis by two-dimensional DNA typing
Nature, 1993
By two-dimensional (2-D) DNA typing a restriction enzyme digest of genomic DNA can be resolved on... more By two-dimensional (2-D) DNA typing a restriction enzyme digest of genomic DNA can be resolved on the basis of both size and base-pair sequence and subsequently analysed by repeat probe hybridization to reveal sequence variants at multiple genomic sites in parallel. The system has been partly automated and allows for large-scale comparative analysis of complex genomes in a cost-effective manner.
[EUROCAT registration of congenital abnormalities and multiple births; aims, methods and results of the Dutch share of the project 1981-1983]
Nederlands tijdschrift voor geneeskunde
The American Journal of Human Genetics
The power to detect departures from the theoretical proportion of new mutants in X-linked lethal ... more The power to detect departures from the theoretical proportion of new mutants in X-linked lethal disorders has been analyzed for several types of segregation analysis, including methods based on completely linked restriction fragment length polymorphisms. It is shown that all methods require large sample sizes in order to detect even large differences between male and female mutation rates. Ascertainment bias is shown to have a great effect on the outcome of the segregation analysis. All reviewed studies concerning the proportion of new mutants in Duchenne muscular dystrophy, whether they claimed equality or inequality between the male and female mutation rates, give insufficient evidence because of ascertainment bias and a too low power.
Using artificial intelligence languages for the calculation of inbredding coefficients - new tools for an old problem: J. L. Dupouey, Comput. Biol Med 17, 71-74 (1987)
Pattern Recognition
Raster images and measurement with a Vickers M86 scanning microdensitometer and interferometer by computer control
Journal of Microscopy
ABSTRACT
Rapid Screening for ΔF508 Deletion in Cystic Fibrosis
[Indications for an increased risk of neural tube defects in pregnancies following ovulation induction and (or) in-vitro fertilization]
Nederlands tijdschrift voor geneeskunde
Several authors have reported a possible association between IVF or induction of ovulation on the... more Several authors have reported a possible association between IVF or induction of ovulation on the one hand and the occurrence of neural tube defects on the other hand. Here a review is given of recent literature on this subject, including data available from The Netherlands. Collaborative epidemiologic studies are needed to evaluate the potential risks. In individual pregnancies prenatal examination is advised. In spontaneous abortions fetal pathological evaluation is desirable.
Cancer Research
A cytogenetic analysis of ten seminomas has been carried out after direct harvesting of the tumor... more A cytogenetic analysis of ten seminomas has been carried out after direct harvesting of the tumor cells. Modal chromosome numbers ranged from 63 to 112. These numbers were in agreement with flow cytometric determination of the DNA content of the tumors. Eight tumors had at least one copy of an i(12p) among other chromosomal abnormalities. Two seminomas lacked the i(12p).
Family distances as a measure of hidden consanguinity. A reappraisal
Human Heredity
We compared the family distances of patients with autosomal recessive disorders with those of a r... more We compared the family distances of patients with autosomal recessive disorders with those of a random control group and a matched control group. Only in the great-grandparental generation were weak-significant differences found. We also found that the family distances of persons with an urban origin were significantly larger than those of persons with a rural origin. In our study, family distance seems to be a more powerful measure of hidden consanguinity than the parental distance.
Expected size of shared halotypes surrounding a common disease gene
The American Journal of Human Genetics
ABSTRACT
Variable age of onset in hereditary nonpolyposis colorectal cancer: Clinical implications
Gastroenterology
Exploring haplotype sharing methods in general and isolated populations to detect gene(s) of a complex genetic trait
Genetic Epidemiology
We applied a new haplotype sharing method to the simulated Genetic Analysis Workshop 12 data for ... more We applied a new haplotype sharing method to the simulated Genetic Analysis Workshop 12 data for both isolated and general populations without knowledge of the disease model, using affection status as phenotype and three different sample sizes. The highest peak for the mean sharing of the haplotypes was found in the isolated population for the markers D06G034 and D06G035, which flank the candidate genes located on chromosome 6, with -log10(p) values of 2.9 and 7.0 in the moderate and large study samples, respectively. The whole genome screen detected three further loci with -log10(p) values of 3.0, which turned out to be false positives. None of the true gene loci were detected in the general population even in the largest sample. The test of linkage disequilibrium based on excess haplotype sharing over the linkage equilibrium expectation revealed z-values one order of magnitude higher in the isolated than in the general population. This approach appears to be promising for mapping genes of complex diseases depending on population characteristics.
Mutation frequency of cystic fibrosis transmembrane regulator is not increased in oligozoospermic male candidates for intracytoplasmic sperm injection
Fertility and Sterility
To examine the frequency of anomalies of the vas deferens and the frequency of mutations of the c... more To examine the frequency of anomalies of the vas deferens and the frequency of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in male candidates for intracytoplasmic sperm injection (ICSI) who had severe oligoasthenoteratozoospermia. The clinical data for male candidates for ICSI were studied. The three most frequent cystic fibrosis (CF)-causing CFTR mutations in the Dutch population (deltaF508, A455E, and G542X) and the three most frequent CFTR mutations potentially causing congenital bilateral absence of the vas deferens (CBAVD) in the Dutch population (deltaF508, R117H, and IVS8-5T) were analyzed. Delta I507 is also detected by the deltaF508 test. Samples of DNA from patients identified as CFTR mutation carriers were subjected to denaturing gradient gel electrophoresis analysis with use of a two-dimensional electrophoretic technique. University-based center for reproductive medicine and clinical genetics. Male candidates for ICSI who had oligoasthenoteratozoospermia and no history of operative sterilization and refertilization. Males with a chromosomal aberration or a Y-chromosome microdeletion were excluded. Semen and blood samples were collected from the patients at their first visit to the clinic. Frequency of anomalies of the vas deferens and frequency of mutations of the CFTR gene in male candidates for ICSI who had oligoasthenoteratozoospermia. None of the patients had abnormalities of the vas deferens at physical examination. In 4 of the 150 chromosomes (75 patients), a CFTR mutation was found, yielding a CFTR mutation frequency of 2.7% (95% confidence interval, 1.0-6.7%). None of the patients had two CFTR mutations. The frequency of congenital abnormalities of the vas deferens in patients with oligoasthenoteratozoospermia is low. The frequencies of the CFTR mutations identified in this cohort did not differ significantly from the frequencies found in the normal Dutch population.
Haplotype sharing tests of linkage disequilibrium in a Hutterite asthma data set
Genetic Epidemiology
The Genetic Analysis Workshop 12 genome scan data set for "strict&qu... more The 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.
Under specific culturing conditions cells growing out from bone fragments are considered to be os... more Under specific culturing conditions cells growing out from bone fragments are considered to be osteoblasts. Collagenase pre-treatment is generally applied to the bone fragments to get rid of fibroblast admixture. Since morphologically the cultured osteoblasts cannot be discriminated from fibroblasts, we developed an efficient test to discriminate between both cell types. We compared gene expression profiles of 10 osteoblast and 11 skin fibroblast cultures using a 21K oligonucleotide micro-array. This comparison resulted in 42 genes showing a significantly different expression between the two types of cultured cells. These differentially expressed genes were specifically related to membrane proteins/processes such as cell communication, cell adhesion and receptor activity. Expression differences for six of these genes defined by micro-array analysis were confirmed by real-time RT-PCR. VCAM1, KIAA1644, FGFR2 and COL27A1 had a higher expression in osteoblasts, whereas IMP-3 and MME were higher expressed in fibroblasts. Since for all six genes differences between all pairs of individual cultures were fully consistent, expression analysis of these genes provides a fast and efficient test to discriminate between osteoblasts and fibroblasts.
Screening for cystic fibrosis. A comparative study
Acta paediatrica
A neonatal screening program for CF by determination of albumin in meconium was performed in the ... more A neonatal screening program for CF by determination of albumin in meconium was performed in the north eastern part of the Netherlands from 1973 to 1979. In this period 94,043 newborns were screened and 116,953 were not. A follow-up study of CF patients in the above cohorts was started in 1980. The purposes of this study were to evaluate the effects of early diagnosis and treatment in CF patients by comparing the outcome in the two groups of patients. Although the results indicate that very early diagnosis and treatment have a beneficial effect on outcome, more studies are needed before a definite answer can be given as to whether or not mass neonatal screening should be started.
The American Journal of Human Genetics
Nonpenetrance of the inherited mutation responsible for retinoblastoma has been reported. By DNA ... more Nonpenetrance of the inherited mutation responsible for retinoblastoma has been reported. By DNA analysis in families with hereditary retinoblastoma, it is possible to identify healthy individuals in whom the mutation is nonpenetrant. This requires the use of DNA markers both within and flanking the retinoblastoma gene. We have analyzed the segregation of several markers in 19 families (69 meioses) with hereditary retinoblastoma. In two families a carrier was identified who showed nonpenetrance of the mutation predisposing to retinoblastoma. The intragenic markers were informative in 15 pedigrees. The use of flanking markers from the same chromosomal region caused an increase of the number of informative families to 18. No crossing-over within the gene was observed. In one family an inherited deletion involving one of the RB1 alleles was detected. Our findings emphasize the use of a combination of both intragenic and flanking markers to obtain both the highest reliability of carrier detection in families with hereditary retinoblastoma and an accurate estimate of the frequency of nonpenetrance.
The American Journal of Human Genetics
C-cell hyperplasia precedes the development of medullary thyroid carcinoma in multiple endocrine ... more C-cell hyperplasia precedes the development of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A (MEN2A). Identification of abnormal calcitonin levels after a provocative stimulus is a technique that has been widely used to diagnose this preneoplastic condition in an early stage during the development of medullary thyroid carcinoma, when total thyroidectomy is likely to be curative. In a MEN2A kindred, we identified seven individuals with abnormal calcitonin test results, whose carrier state was questionable. Five of these people were thyroidectomized, and C-cell hyperplasia was diagnosed. Four of these individuals were the offspring of a mother who is at risk for the development of MEN2A but who has had normal calcitonin test results throughout the years and of a father who is not at risk but who has had abnormal test results over a period of 10 years, without evidence of progressive elevation. None of these people developed other manifestations of MEN2A. DNA analysis using markers linked to the MEN2A gene demonstrated, with >99% likelihood, that none of the individuals who could be genotyped was a gene carrier. C-cell hyperplasia due to some mechanism other than the presence of the MEN2A gene may also occur in MEN2A kindreds. DNA analysis offers an important additional tool for proper diagnosis in the clinical management of MEN2A families.
Van Echten-Arends, J. et al. No recurrent structural abnormalities in germ cell tumors of the adult testis apart from i(12p). Genes Chromosom. Cancer 14, 133-144
Genes Chromosomes and Cancer
ABSTRACT
Biotechnology Progress
The early factors inducing insulin resistance are not known. Therefore, we are interested in stud... more The early factors inducing insulin resistance are not known. Therefore, we are interested in studying the secretome of the human visceral adipose tissue as a potential source of unknown peptides and proteins inducing insulin resistance. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry is a high-throughput proteomics technology to generate peptide and protein profiles (MS spectra). To obtain good quality and reproducible data from SELDI-TOF, many factors in the sample pretreatment and SELDI protocol should be optimized. To identify the optimal combination of factors resulting in the best and the most reproducible spectra, we designed an experiment where factors were varied systematically according to a fractional factorial design. In this study, seven protein chip preparation protocol factors were tested in 32 experiments. The main effects of these factors and their interactions contributing to the best quality spectra were identified by ANOVA...
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Papers by Gerard J te Meerman