Gerard Meerman | University Medical Center Groningen (original) (raw)

Papers by Gerard Meerman

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.

American journal of human genetics, 1993

In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size... more In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core probes. The 2-D DNA typing method generates a large amount of information on polymorphic loci per gel. Here we demonstrate the potential usefulness of 2-D DNA typing in an empirical linkage study on the red factor in cattle, and we show an example of the 2-D DNA typing analysis of a human pedigree. The power efficiency of 2-D DNA typing in general is compared with that of single-locus typing by simulation. The results indicate that, although 2-D DNA typing is very efficient in generating data on polymorphic loci, its power to detect linkage is lower than single-locus typing, because it is not obvious whether a spot represents the presence of one or two alleles. It is possible to compensate f...

Human Genetics, 1990

Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation not... more Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation notably in liver and brain tissue. Linkage of the WD locus (WND) to ESD at 13q14 was first shown by studies in families of Middle Eastern origin using the isozymic polymorphism of esterase D. Using RFLPs detected by the ESD cDNA we could not confirm this reported close

Scandinavian Journal of Gastroenterology, 2003

Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly unde... more Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly understood. Apart from environmental factors, inheritance contributes to IBD. Family studies show an increased risk among family members of a patient with IBD, particularly among first-degree relatives. In twin studies, concordance for disease type and localization is observed. In genetically isolated groups there is a higher prevalence of IBD. For instance. Ashkenazi Jews carry the highest risk. Further evidence comes from animal species that spontaneously develop IBD. Unlike Mendelian inheritance, in complex genetic diseases like IBD, genes are expected to be low penetrant and therefore less prone to selection, which results in higher expected gene frequencies. NOD2/CARD15, the first gene associated with IBD, is a polymorphic gene involved in the innate immune system. The gene has over 60 variations. Three of these play a role in 27% of patients with CD, with a predilection for patients with ileal disease. Genetics plays an important role in unravelling the pathogenesis of IBD leading to possible new therapeutic approaches.

Psychiatric Genetics, 2007

Objectives The stress response is related to both physiological and psychological factors and is ... more Objectives The stress response is related to both physiological and psychological factors and is strongly marked by a neuroendocrine component. Genetic factors are believed to underlie individual differences in the degree of stress resilience and thereby contribute in determining susceptibility to stress-related pathologies like major depressive disorder (MDD). Little, however, is known about the genetic influence on the endocrine and behavioural stress response in relation to MDD.

Pediatric Radiology, 1985

Three systems are described for chest radiograph scoring in cystic fibrosis patients: the Shwachm... more Three systems are described for chest radiograph scoring in cystic fibrosis patients: the Shwachman-Kulczycki, the Chrispin-Norman and the Brasfield method. Sixty chest radiographs of 39 patients of different ages have been independently scored by two radiologists according to the three methods. No statistical differences between the methods could be demonstrated. The Chrispin-Norman method is recommended as the best choice because differences in scoring appeared better interpretable. A significant increase in precision could be achieved by combining the scores of the three methods.

Journal of Medical Genetics, 1995

A formula to calculate recurrence risk for germline mosaicism published by Hartl in 1971 has been... more A formula to calculate recurrence risk for germline mosaicism published by Hartl in 1971 has been updated to include marker information. For practical genetic counselling new, more elaborate tables are given. (J Med Genet 1995;32:102-104) In 1974 Murphy et all concluded "From the clinical standpoint the main implication is that it provides reassurance that, in any realistic size of family, ignoring the effect of gonadal mosaicism will have little effect on the estimate of the risk for the next child". This paper has been referred to many times in papers about mosaicism. A paper by Hartl,' entitled "Recurrence risk for germinal mosaics", gives formulae to calculate recurrence risks, correcting for the number of affected and unaffected sibs. This paper will discuss the impact of modem molecular genetic techniques on the recurrence risk for gonadal mosaicism.

Genetic Epidemiology, 2003

Haplotype sharing analysis was used to investigate the association of affection status with singl... more Haplotype sharing analysis was used to investigate the association of affection status with single nucleotide polymorphism (SNP) haplotypes within candidate gene 1 in one sample each from the isolated and the general population of Genetic Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct influence on affection and harbors more than 70 SNPs. Haplotype sharing analysis depends heavily on previous haplotype estimation. Using GENEHUNTER haplotypes, strong evidence was found for most SNPs in the isolated population sample, thus providing evidence for an involvement of this gene, but the maximum -log(10)(p) values for the haplotype sharing statistics (HSS) test statistic did not correspond to the location of the true variant in either population. In comparison, transmission disequilibrium test (TDT) analysis showed the strongest results at the disease-causing variant in both populations, and these were outstanding in the general population. In this example, TDT analysis appears to perform better than HSS in identifying the disease-causing variant, using SNPs within a candidate gene in an outbred population. Simulations showed that the performance of HSS is hampered by closely spaced SNPs in strong linkage disequilibrium with the functional variant and by ambiguous haplotypes.

Genetic Epidemiology, 1997

The number of identical deleterious mutations present in a population may become very large, depe... more The number of identical deleterious mutations present in a population may become very large, depending on the combined effect of genetic drift, population growth and limited negative selection. The distribution of the length of the shared area between two random chromosomes carrying the mutations has been investigated for a number of generations varying from 20-100 since introduction. The consequences for investigations using association and haplotype sharing methods are discussed.

Genetic Epidemiology, 1997

In diseases with a complex mode of inheritance, families with multiple affected individuals are d... more In diseases with a complex mode of inheritance, families with multiple affected individuals are difficult to ascertain. The haplotype sharing statistic (HSS) uses (hidden) co-ancestry between affected individuals from a founder population. These affected individuals will likely not only share the same mutation(s), but also the surrounding haplotype. We show that this method gives a low false positive rate, but does not detect genes in the nuclear families of Problem 2A of the GAW data. We also give evidence based on simulations and empirical studies in real population based data that the HSS method has statistical power.

Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1995

In a founder population patients with a genetic disease are likely to share predisposing genes fr... more In a founder population patients with a genetic disease are likely to share predisposing genes from a common ancestor. We show that, depending on the distance of the relationship, patients are expected to share extended segments of DNA around the disease gene. Because of the size of the shared segment, a genomic search with DNA markers for such shared segments, identity by descent (IBD) mapping, can efficiently find the map position of genes, particularly due to genetic drift leading to reduction of heterogeneity and the large number of meioses that is implicitly observed. The statistical power of this method and the approximate cost are given as a function of the density of the map of tested markers and the number of generations since a common ancestor. Initial marker spacings between 5 and 15 centiMorgans are shown to be optimal. IBD mapping is applicable to many genetic diseases, because it does not presuppose a specific genetic model.

Annals of Diagnostic Pathology, 2000

In hematoxylin-eosin-stained sections of 20 pediatric sarcomas the mitotic index was assessed by ... more In hematoxylin-eosin-stained sections of 20 pediatric sarcomas the mitotic index was assessed by four experienced pathologists and four less-experienced observers without prior instructions. In adjacent sections immunolabeled for MIB-1, the proliferation index was assessed as the estimated percentage of labeled cells in the tumor cell population. ANOVA revealed that the variation between tumors explained 77% of the variation in mitotic indices in the group of experienced observers compared with 49% in the less experienced group. The variation between tumors explained 64% of the variation in proliferation indices in the experienced group and 71% in the less experienced group. The proliferation indices showed less variation between observers than the mitotic indices. No correlation was found between mitotic and proliferation indices. The results suggest that training is an important factor in the reliability of mitotic counting. The use of proliferation markers has a higher reproducibility, especially in less-experienced observers. However, for clinical use it has the disadvantage of being the more expensive, more time-consuming technique; moreover, the biological significance of proliferation has not been established and may differ from that of mitotic activity.

Neurogenetics, 2001

Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an associ... more Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an association of MS with specific human leukocyte antigen (HLA) types has been known for almost 30 years, the nature of this relationship has remained unclear. Furthermore, genetic resolution sufficient to implicate a specific gene in the HLA region has not been achieved. Many loci in the HLA region have been found to be significantly associated with MS, which is largely explained by the extended haplotype sharing and varying marker informativity of the region. We have determined 248 haplotypes of MS patients from the population of the northern Netherlands and 226 haplotypes of their relatives as controls using a set of 22 microsatellite markers covering the HLA region. The data were analyzed using standard association methods and a new statistical method, haplotype sharing statistics (HSS). Haplotype sharing statistics determines the extent of haplotype sharing for all pairs of haplotypes of pa...

Urology, 2001

ing in an effort to determine the best method to make prostate biopsy a less unpleasant outpatien... more ing in an effort to determine the best method to make prostate biopsy a less unpleasant outpatient procedure. REFERENCES 1. Collins GN, Lloyd SN, Hehir M, et al: Multiple transrectal ultrasound-guided prostatic biopsies-true morbidity and patient acceptance. Br J Urol 71: 460, 1993. 2. Wu CL, Carter HB, Naqibuddin M, et al: Effect of local anesthetics on patient recovery after transrectal biopsy. Urology 57: 925-929, 2001. 3. Nash PA, Bruce JE, Indudhara R, et al: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol 155: 607-609, 1996.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002

This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or ca... more This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or cancer or that are in strong linkage disequilibrium with colorectal adenoma and/or cancer causing variants. A pooled analysis was performed for 30 polymorphisms in 20 different genes that have been reported in more than one colorectal adenoma or cancer study. An association with colorectal cancer was found for seven polymorphisms in seven genes reported in more than one study; no associations were found with colorectal adenoma. Four of the polymorphisms exhibited an increased colorectal cancer risk [GSTT1, NAT2 (phenotype), HRAS1, and ALDH2]. Two others [MTHFR, Tp53 (intron 3)] exhibited a decreased risk. For the tumor necrosis factor (TNF)a polymorphism of the TNF-alpha gene, one allele was associated with an increased risk (a2 allele) and two other TNFa alleles with decreased risks (a5 and a13 allele). No association with colorectal adenoma and/or cancer was detected for 23 other polymor...

American journal of human genetics, 1993

In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size... more In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core probes. The 2-D DNA typing method generates a large amount of information on polymorphic loci per gel. Here we demonstrate the potential usefulness of 2-D DNA typing in an empirical linkage study on the red factor in cattle, and we show an example of the 2-D DNA typing analysis of a human pedigree. The power efficiency of 2-D DNA typing in general is compared with that of single-locus typing by simulation. The results indicate that, although 2-D DNA typing is very efficient in generating data on polymorphic loci, its power to detect linkage is lower than single-locus typing, because it is not obvious whether a spot represents the presence of one or two alleles. It is possible to compensate f...

Thyroid, 2001

Differentiated thyroid cancer is a rare disease and until recently was considered to be sporadic.... more Differentiated thyroid cancer is a rare disease and until recently was considered to be sporadic. However, increasing evidence has been found for a genetic basis of this disease. In approximately 5% of patients the differentiated thyroid cancer is dominantly inherited. Several families with different syndromes, of which differentiated thyroid cancer is a feature, have already been described. However, until now, single genes explain only a minority of cases. We hypothesize that differentiated thyroid cancer is a polygenic disease. Data from epidemiologic studies, about occult and multifocal carcinomas and the different response to specific risk factors contribute to this hypothesis.

BMC Proceedings, 2007

We propose two new haplotype-sharing methods for identifying disease loci: the haplotype sharing ... more We propose two new haplotype-sharing methods for identifying disease loci: the haplotype sharing statistic (HSS), which compares length of shared haplotypes between cases and controls, and the CROSS test, which tests whether a case and a control haplotype show less sharing than two random haplotypes.

Cytometry, 1999

To investigate the possibilities of sperm head volume as a sorting criterion for gender preselect... more To investigate the possibilities of sperm head volume as a sorting criterion for gender preselection, we determined the magnitude of the difference in volume of X-and Y-chromosome-bearing bull sperm heads. Materials and Methods: Bovine sperm heads were sorted on the basis of their DNA content in X-and Y-chromosomebearing fractions, using an existing flow-cytometric technique. Images of sperm heads of both populations were recorded using Differential Interference Contrast (DIC) microscopy. After reconstructing the DIC images, the area and the optical thickness of sperm heads of both populations were determined. Results: We found a difference in volume of X-and Y-bearing bovine sperm heads matching the difference in DNA content (3.5-4%).

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.

American journal of human genetics, 1993

In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size... more In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core probes. The 2-D DNA typing method generates a large amount of information on polymorphic loci per gel. Here we demonstrate the potential usefulness of 2-D DNA typing in an empirical linkage study on the red factor in cattle, and we show an example of the 2-D DNA typing analysis of a human pedigree. The power efficiency of 2-D DNA typing in general is compared with that of single-locus typing by simulation. The results indicate that, although 2-D DNA typing is very efficient in generating data on polymorphic loci, its power to detect linkage is lower than single-locus typing, because it is not obvious whether a spot represents the presence of one or two alleles. It is possible to compensate f...

Human Genetics, 1990

Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation not... more Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation notably in liver and brain tissue. Linkage of the WD locus (WND) to ESD at 13q14 was first shown by studies in families of Middle Eastern origin using the isozymic polymorphism of esterase D. Using RFLPs detected by the ESD cDNA we could not confirm this reported close

Scandinavian Journal of Gastroenterology, 2003

Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly unde... more Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly understood. Apart from environmental factors, inheritance contributes to IBD. Family studies show an increased risk among family members of a patient with IBD, particularly among first-degree relatives. In twin studies, concordance for disease type and localization is observed. In genetically isolated groups there is a higher prevalence of IBD. For instance. Ashkenazi Jews carry the highest risk. Further evidence comes from animal species that spontaneously develop IBD. Unlike Mendelian inheritance, in complex genetic diseases like IBD, genes are expected to be low penetrant and therefore less prone to selection, which results in higher expected gene frequencies. NOD2/CARD15, the first gene associated with IBD, is a polymorphic gene involved in the innate immune system. The gene has over 60 variations. Three of these play a role in 27% of patients with CD, with a predilection for patients with ileal disease. Genetics plays an important role in unravelling the pathogenesis of IBD leading to possible new therapeutic approaches.

Psychiatric Genetics, 2007

Objectives The stress response is related to both physiological and psychological factors and is ... more Objectives The stress response is related to both physiological and psychological factors and is strongly marked by a neuroendocrine component. Genetic factors are believed to underlie individual differences in the degree of stress resilience and thereby contribute in determining susceptibility to stress-related pathologies like major depressive disorder (MDD). Little, however, is known about the genetic influence on the endocrine and behavioural stress response in relation to MDD.

Pediatric Radiology, 1985

Three systems are described for chest radiograph scoring in cystic fibrosis patients: the Shwachm... more Three systems are described for chest radiograph scoring in cystic fibrosis patients: the Shwachman-Kulczycki, the Chrispin-Norman and the Brasfield method. Sixty chest radiographs of 39 patients of different ages have been independently scored by two radiologists according to the three methods. No statistical differences between the methods could be demonstrated. The Chrispin-Norman method is recommended as the best choice because differences in scoring appeared better interpretable. A significant increase in precision could be achieved by combining the scores of the three methods.

Journal of Medical Genetics, 1995

A formula to calculate recurrence risk for germline mosaicism published by Hartl in 1971 has been... more A formula to calculate recurrence risk for germline mosaicism published by Hartl in 1971 has been updated to include marker information. For practical genetic counselling new, more elaborate tables are given. (J Med Genet 1995;32:102-104) In 1974 Murphy et all concluded "From the clinical standpoint the main implication is that it provides reassurance that, in any realistic size of family, ignoring the effect of gonadal mosaicism will have little effect on the estimate of the risk for the next child". This paper has been referred to many times in papers about mosaicism. A paper by Hartl,' entitled "Recurrence risk for germinal mosaics", gives formulae to calculate recurrence risks, correcting for the number of affected and unaffected sibs. This paper will discuss the impact of modem molecular genetic techniques on the recurrence risk for gonadal mosaicism.

Genetic Epidemiology, 2003

Haplotype sharing analysis was used to investigate the association of affection status with singl... more Haplotype sharing analysis was used to investigate the association of affection status with single nucleotide polymorphism (SNP) haplotypes within candidate gene 1 in one sample each from the isolated and the general population of Genetic Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct influence on affection and harbors more than 70 SNPs. Haplotype sharing analysis depends heavily on previous haplotype estimation. Using GENEHUNTER haplotypes, strong evidence was found for most SNPs in the isolated population sample, thus providing evidence for an involvement of this gene, but the maximum -log(10)(p) values for the haplotype sharing statistics (HSS) test statistic did not correspond to the location of the true variant in either population. In comparison, transmission disequilibrium test (TDT) analysis showed the strongest results at the disease-causing variant in both populations, and these were outstanding in the general population. In this example, TDT analysis appears to perform better than HSS in identifying the disease-causing variant, using SNPs within a candidate gene in an outbred population. Simulations showed that the performance of HSS is hampered by closely spaced SNPs in strong linkage disequilibrium with the functional variant and by ambiguous haplotypes.

Genetic Epidemiology, 1997

The number of identical deleterious mutations present in a population may become very large, depe... more The number of identical deleterious mutations present in a population may become very large, depending on the combined effect of genetic drift, population growth and limited negative selection. The distribution of the length of the shared area between two random chromosomes carrying the mutations has been investigated for a number of generations varying from 20-100 since introduction. The consequences for investigations using association and haplotype sharing methods are discussed.

Genetic Epidemiology, 1997

In diseases with a complex mode of inheritance, families with multiple affected individuals are d... more In diseases with a complex mode of inheritance, families with multiple affected individuals are difficult to ascertain. The haplotype sharing statistic (HSS) uses (hidden) co-ancestry between affected individuals from a founder population. These affected individuals will likely not only share the same mutation(s), but also the surrounding haplotype. We show that this method gives a low false positive rate, but does not detect genes in the nuclear families of Problem 2A of the GAW data. We also give evidence based on simulations and empirical studies in real population based data that the HSS method has statistical power.

Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1995

In a founder population patients with a genetic disease are likely to share predisposing genes fr... more In a founder population patients with a genetic disease are likely to share predisposing genes from a common ancestor. We show that, depending on the distance of the relationship, patients are expected to share extended segments of DNA around the disease gene. Because of the size of the shared segment, a genomic search with DNA markers for such shared segments, identity by descent (IBD) mapping, can efficiently find the map position of genes, particularly due to genetic drift leading to reduction of heterogeneity and the large number of meioses that is implicitly observed. The statistical power of this method and the approximate cost are given as a function of the density of the map of tested markers and the number of generations since a common ancestor. Initial marker spacings between 5 and 15 centiMorgans are shown to be optimal. IBD mapping is applicable to many genetic diseases, because it does not presuppose a specific genetic model.

Annals of Diagnostic Pathology, 2000

In hematoxylin-eosin-stained sections of 20 pediatric sarcomas the mitotic index was assessed by ... more In hematoxylin-eosin-stained sections of 20 pediatric sarcomas the mitotic index was assessed by four experienced pathologists and four less-experienced observers without prior instructions. In adjacent sections immunolabeled for MIB-1, the proliferation index was assessed as the estimated percentage of labeled cells in the tumor cell population. ANOVA revealed that the variation between tumors explained 77% of the variation in mitotic indices in the group of experienced observers compared with 49% in the less experienced group. The variation between tumors explained 64% of the variation in proliferation indices in the experienced group and 71% in the less experienced group. The proliferation indices showed less variation between observers than the mitotic indices. No correlation was found between mitotic and proliferation indices. The results suggest that training is an important factor in the reliability of mitotic counting. The use of proliferation markers has a higher reproducibility, especially in less-experienced observers. However, for clinical use it has the disadvantage of being the more expensive, more time-consuming technique; moreover, the biological significance of proliferation has not been established and may differ from that of mitotic activity.

Neurogenetics, 2001

Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an associ... more Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an association of MS with specific human leukocyte antigen (HLA) types has been known for almost 30 years, the nature of this relationship has remained unclear. Furthermore, genetic resolution sufficient to implicate a specific gene in the HLA region has not been achieved. Many loci in the HLA region have been found to be significantly associated with MS, which is largely explained by the extended haplotype sharing and varying marker informativity of the region. We have determined 248 haplotypes of MS patients from the population of the northern Netherlands and 226 haplotypes of their relatives as controls using a set of 22 microsatellite markers covering the HLA region. The data were analyzed using standard association methods and a new statistical method, haplotype sharing statistics (HSS). Haplotype sharing statistics determines the extent of haplotype sharing for all pairs of haplotypes of pa...

Urology, 2001

ing in an effort to determine the best method to make prostate biopsy a less unpleasant outpatien... more ing in an effort to determine the best method to make prostate biopsy a less unpleasant outpatient procedure. REFERENCES 1. Collins GN, Lloyd SN, Hehir M, et al: Multiple transrectal ultrasound-guided prostatic biopsies-true morbidity and patient acceptance. Br J Urol 71: 460, 1993. 2. Wu CL, Carter HB, Naqibuddin M, et al: Effect of local anesthetics on patient recovery after transrectal biopsy. Urology 57: 925-929, 2001. 3. Nash PA, Bruce JE, Indudhara R, et al: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol 155: 607-609, 1996.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002

This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or ca... more This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or cancer or that are in strong linkage disequilibrium with colorectal adenoma and/or cancer causing variants. A pooled analysis was performed for 30 polymorphisms in 20 different genes that have been reported in more than one colorectal adenoma or cancer study. An association with colorectal cancer was found for seven polymorphisms in seven genes reported in more than one study; no associations were found with colorectal adenoma. Four of the polymorphisms exhibited an increased colorectal cancer risk [GSTT1, NAT2 (phenotype), HRAS1, and ALDH2]. Two others [MTHFR, Tp53 (intron 3)] exhibited a decreased risk. For the tumor necrosis factor (TNF)a polymorphism of the TNF-alpha gene, one allele was associated with an increased risk (a2 allele) and two other TNFa alleles with decreased risks (a5 and a13 allele). No association with colorectal adenoma and/or cancer was detected for 23 other polymor...

American journal of human genetics, 1993

In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size... more In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core probes. The 2-D DNA typing method generates a large amount of information on polymorphic loci per gel. Here we demonstrate the potential usefulness of 2-D DNA typing in an empirical linkage study on the red factor in cattle, and we show an example of the 2-D DNA typing analysis of a human pedigree. The power efficiency of 2-D DNA typing in general is compared with that of single-locus typing by simulation. The results indicate that, although 2-D DNA typing is very efficient in generating data on polymorphic loci, its power to detect linkage is lower than single-locus typing, because it is not obvious whether a spot represents the presence of one or two alleles. It is possible to compensate f...

Thyroid, 2001

Differentiated thyroid cancer is a rare disease and until recently was considered to be sporadic.... more Differentiated thyroid cancer is a rare disease and until recently was considered to be sporadic. However, increasing evidence has been found for a genetic basis of this disease. In approximately 5% of patients the differentiated thyroid cancer is dominantly inherited. Several families with different syndromes, of which differentiated thyroid cancer is a feature, have already been described. However, until now, single genes explain only a minority of cases. We hypothesize that differentiated thyroid cancer is a polygenic disease. Data from epidemiologic studies, about occult and multifocal carcinomas and the different response to specific risk factors contribute to this hypothesis.

BMC Proceedings, 2007

We propose two new haplotype-sharing methods for identifying disease loci: the haplotype sharing ... more We propose two new haplotype-sharing methods for identifying disease loci: the haplotype sharing statistic (HSS), which compares length of shared haplotypes between cases and controls, and the CROSS test, which tests whether a case and a control haplotype show less sharing than two random haplotypes.

Cytometry, 1999

To investigate the possibilities of sperm head volume as a sorting criterion for gender preselect... more To investigate the possibilities of sperm head volume as a sorting criterion for gender preselection, we determined the magnitude of the difference in volume of X-and Y-chromosome-bearing bull sperm heads. Materials and Methods: Bovine sperm heads were sorted on the basis of their DNA content in X-and Y-chromosomebearing fractions, using an existing flow-cytometric technique. Images of sperm heads of both populations were recorded using Differential Interference Contrast (DIC) microscopy. After reconstructing the DIC images, the area and the optical thickness of sperm heads of both populations were determined. Results: We found a difference in volume of X-and Y-bearing bovine sperm heads matching the difference in DNA content (3.5-4%).