28 research outputs found
A logic programming approach to pedigree analysis.
No full textHet analyseren van fenotypische variatie van genetische markers en aandoeningen in stambomen is van groot belang om inzicht te krijgen in de lokalisatie van erfelijke factoren. De rekentechnische problemen die hiebij een rol spelen zijn tweeërlei: als een groot aantal eigenschappen tegelijkertijd wordt geanalyseerd, wordt het aantal mogelijke combinaties van eigenschappen erg groot, terwijl ook een ingewilkkelde familie rekentechnisch moeilijk te analyseren is. ...
Zie: Samenvatting
A logic programming approach to pedigree analysis.
No full textHet analyseren van fenotypische variatie van genetische markers en aandoeningen in stambomen is van groot belang om inzicht te krijgen in de lokalisatie van erfelijke factoren. De rekentechnische problemen die hiebij een rol spelen zijn tweeërlei: als een groot aantal eigenschappen tegelijkertijd wordt geanalyseerd, wordt het aantal mogelijke combinaties van eigenschappen erg groot, terwijl ook een ingewilkkelde familie rekentechnisch moeilijk te analyseren is. ... Zie: Samenvattin
A logic programming approach to pedigree analysis.
No full textHet analyseren van fenotypische variatie van genetische markers en aandoeningen in stambomen is van groot belang om inzicht te krijgen in de lokalisatie van erfelijke factoren. De rekentechnische problemen die hiebij een rol spelen zijn tweeërlei: als een groot aantal eigenschappen tegelijkertijd wordt geanalyseerd, wordt het aantal mogelijke combinaties van eigenschappen erg groot, terwijl ook een ingewilkkelde familie rekentechnisch moeilijk te analyseren is. ... Zie: Samenvattin
A logic programming approach to pedigree analysis.
No full textHet analyseren van fenotypische variatie van genetische markers en aandoeningen in stambomen is van groot belang om inzicht te krijgen in de lokalisatie van erfelijke factoren. De rekentechnische problemen die hiebij een rol spelen zijn tweeërlei: als een groot aantal eigenschappen tegelijkertijd wordt geanalyseerd, wordt het aantal mogelijke combinaties van eigenschappen erg groot, terwijl ook een ingewilkkelde familie rekentechnisch moeilijk te analyseren is. ... Zie: Samenvattin
A Haplotype Sharing Method for Determining the Relative Age of SNP Alleles
No full textThere are two aspects regarding the age of alleles that are relevant as indicators of the timing of mutational events. The first is to know which alleles are species-specific; the second is about the time of origin of species-specific alleles. Both aspects can be analyzed using haplotype-sharing methods, by using the length of shared haplotypes as a measure of the speed of coalescence to common ancestors. The availability of sequence data for closely related species makes it possible to infer the original SNP allele. The allele present in more than one species is the original allele. In general, original alleles are expected to be more frequent, because the cumulative effects of genetic drift determine the maximum frequency a new mutant can reach. The human species is relatively young, and founder effects are still observable as extended linkage disequilibrium. Coalescence to a single founder takes place in human populations over a time frame that is so small that original haplotypes spanning several markers are still observable in current high-density SNP genotyping arrays. We show here that the length of shared haplotypes surrounding alleles is an indicator of the relative ages of alleles, and it is applicable to original and species-specific alleles. Copyright (C) 2009 S. Karger AG, Base
Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands:a population based case-control study
No full text<p>Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects-mainly clefts of the lip/alveolus-with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.</p>
No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis
No full textMalignant transformation may be caused by gene deregulation resulting from specific chromosomal rearrangements, by amplification, by mutations in proto-oncogenes, by loss of tumor suppressor genes, or a combination of these. We investigated the role of numerical and structural chromosomal abnormalities in 102 cytogenetically abnormal cases of primary testicular germ cell tumors of adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell tumors (NS)]. We confirmed that an isochromosome for 12p, i(12p), is the only consistent structural chromosomal abnormality in TGCT, present in about 70% of our cases. Both the frequency and the number of copies of i(12p) are higher in NS than in SE. This may suggest that i(12p) is involved in tumor progression. Besides i(12p), several clonal structural chromosomal abnormalities were found, bur none appeared to be specific. SE and NS had chromosome numbers in the triploid range, with significantly higher numbers in SE than in NS (average modal chromosome number of 73.4 in SE and 65.0 in NS). Both in SE and NS, some chromosomes were significantly underrepresented (e.g., 11, 13, 18, and Y) and others overrepresented (e.g., 7, 8, 12, 21, and X). In SE, a significantly higher copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower number of chromosome 17, compared with NS. These chromosomes may play an important role in the differentiation of TGCT. (C) 1995 Wiley-Liss, Inc
No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis
No full textMalignant transformation may be caused by gene deregulation resulting from specific chromosomal rearrangements, by amplification, by mutations in proto-oncogenes, by loss of tumor suppressor genes, or a combination of these. We investigated the role of numerical and structural chromosomal abnormalities in 102 cytogenetically abnormal cases of primary testicular germ cell tumors of adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell tumors (NS)]. We confirmed that an isochromosome for 12p, i(12p), is the only consistent structural chromosomal abnormality in TGCT, present in about 70% of our cases. Both the frequency and the number of copies of i(12p) are higher in NS than in SE. This may suggest that i(12p) is involved in tumor progression. Besides i(12p), several clonal structural chromosomal abnormalities were found, bur none appeared to be specific. SE and NS had chromosome numbers in the triploid range, with significantly higher numbers in SE than in NS (average modal chromosome number of 73.4 in SE and 65.0 in NS). Both in SE and NS, some chromosomes were significantly underrepresented (e.g., 11, 13, 18, and Y) and others overrepresented (e.g., 7, 8, 12, 21, and X). In SE, a significantly higher copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower number of chromosome 17, compared with NS. These chromosomes may play an important role in the differentiation of TGCT. (C) 1995 Wiley-Liss, Inc.</p
MixupMapper: correcting sample mix-ups in genome-wide datasets increases power to detect small genetic effects
No full textMotivation: Sample mix-ups can arise during sample collection, handling, genotyping or data management. It is unclear how often sample mix-ups occur in genome-wide studies, as there currently are no post hoc methods that can identify these mix-ups in unrelated samples. We have therefore developed an algorithm (MixupMapper) that can both detect and correct sample mix-ups in genome-wide studies that study gene expression levels.
Results: We applied MixupMapper to five publicly available human genetical genomics datasets. On average, 3% of all analyzed samples had been assigned incorrect expression phenotypes: in one of the datasets 23% of the samples had incorrect expression phenotypes. The consequences of sample mix-ups are substantial: when we corrected these sample mix-ups, we identified on average 15% more significant cis-expression quantitative trait loci (cis-eQTLs). In one dataset, we identified three times as many significant cis-eQTLs after correction. Furthermore, we show through simulations that sample mix-ups can lead to an underestimation of the explained heritability of complex traits in genome-wide association datasets.
Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
