AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy

The development of left ventricular hypertrophy (LVH) in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. We investigated whether the angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism, the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and/or plasma renin influence LVH in HCM. Left ventricular mass index (LVMI) and interventricular septal thickness were determined by 2-dimensional echocardiography in 104 genetically independent subjects with HCM. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were measured by immunoradiometric or fluorometric assays, and ACE and AT1-R genotyping were performed by polymerase chain reactions. The ACE D allele did not affect any of the measured parameters except plasma ACE (P<0.04). LVMI was higher (P<0.05) in patients carrying the AT1-R C allele (190+/-8.3 g/m2) than in AA homozygotes (168+/-7.2 g/m2), and similar patterns were observed for interventricular septal thickness (23.0+/-0.7 versus 21. 6+/-0.7 mm) and Wigle score (7.0+/-0.3 versus 6.3+/-0.3). Plasma renin was higher (P=0.05) in carriers of the C allele than in AA homozygotes. Multivariate regression analysis, however, revealed no independent role for renin in the prediction of LVMI. Plasma prorenin and ACE were not affected by the AT1-R A/C1166 polymorphism, nor did the ACE and AT1-R polymorphisms interact with regard to any of the measured parameters. We conclude that the AT1-R C1166 allele modulates the phenotypic expression of hypertrophy in HCM, independently of plasma renin and the ACE I/D polymorphism

A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands

Type 1 diabetes has a substantial genetic component, with consistent evidence for a susceptibility locus in the HLA-DR/DQ region (chromosome 6p) and the insulin gene region (chromosome 11p). Genome scans have identified >18 other genomic regions that may harbor putative type 1 diabetes genes. However, evidence for most regions varies in different data sets. Given the genetic heterogeneity of type 1 diabetes, studies in homogeneous genetically isolated populations may be more successful in mapping susceptibility loci than in complex outbred populations. We describe a genome-wide search in a recently Dutch isolated population. We identified 43 patients that could be traced back to a common ancestor within 15 generations and performed a genome-wide scan using a combined linkage- and association-based approach. In addition to the HLA locus, evidence for type 1 diabetes loci was observed on chromosome 8q24 (marker D8S1128) and on chromosome 17q24 (marker D17S2059). Both the 8q and 17q localization are supported by allele-sharing at adjacent markers in affected individuals. Statistical evidence for a conserved ancestral haplotype was found for chromosome 8q24

Familial hemiplegic migraine locus on 19p13 is involved in the common forms of migraine with and without aura

Migraine is a common neurological disease of two main types: migraine with aura and migraine without aura. Familial clustering suggests that genetic factors are involved in the etiology of migraine. Recently, a gene for familial hemiplegic migraine, a rare autosomal dominant subtype of migraine with aura, was mapped to chromosome 19p13. We tested the involvement of this chromosomal region in 28 unrelated families with the common forms of migraine with and without aura, by following the transmission of the highly informative marker D19S394. Sibpair analysis showed that affected sibs shared the same marker allele more frequently than expected by chance. Our findings thus also suggest the involvement of a gene on 19p13 in the etiology of the common forms of migraine

Refined localization of TSC1 by combined analysis of 9q34 and 16pl3 data in 14 tuberous sclerosis families

Tuberous sclerosis (TSC) is a heterogeneous trait. Since 1990, linkage studies have yielded putative TSC loci on chromosomes 9, 11, 12 and 16. Our current analysis, performed on 14 Dutch and British families, reveals only evidence for loci on chromosome 9q34 (TSC1) and chromosome 16p13 (TSC2). We have found no indication for a third locus for TSC, linked or unlinked to either of these chromosomal regions. The majority of our families shows linkage to chromosome 9. We have refined the candidate region for TSC1 to a region of approximately 5 c M between ABL and ABO

Decolonizar la investigación sobre migraciones : apuntes desde una etnografía colaborativa

En este artículo analizamos los significados asumidos por la idea de "(in)migración(es)" y la categoría de "(in)migrante(s)" en los contextos sociales, políticos y académicos contemporáneos. Resaltando su estrecha relación con el pensamiento de Estado y la colonialidad del poder/saber, nos preguntamos por otros posibles acercamientos a la movilidad humana. Discutimos la etnografía colaborativa, entendida como una metodología decolonial que rechaza las representaciones pasivizantes hegemónicas y aspira a visibilizar los procesos de subjetivación política de las personas junto a las que se investiga. Aportando ejemplos de nuestra propia investigación colaborativa junto a Stop Desahucios-Granada 15M, ilustramos cómo la idea de (in)migración(es) y la categoría "(in)migrante(s)" se han materializado en nuestro contexto, que se encuentra definido por el activismo político y no había sido previamente alterizado como "migratorio". Concluimos resaltando la ambivalencia implícita en estas dos expresiones y reflexionamos sobre los pros y los contras implícitos en su uso.In this paper we analyze the meaning of "immigration" and "immigrant" within contemporary social, political and academic contexts. We emphasize their narrow relation with State thought and the coloniality of power/knowledge and search for alternative approaches to human mobility. With this aim, we discuss collaborative ethnography as a decolonial methodology addressed to visibilize the political subjectivation processes of the people we research with. Drawing on examples from our own collaborative research with Stop Evictions-Granada 15M, we show how the idea of "immigration" and the category "immigrants" have come into being within our field, a space of political activism which had not been previously constructed as a "migratory context". We conclude underlining the ambivalence implicit in the two aforementioned concepts and discuss the pros and cons of using them

Facioscapulohumeral muscular dystrophy in the Dutch population

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Variance-component analysis of obesity in Type 2 Diabetes confirms loci on chromosomes 1q and 11q

To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome-wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of ~75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores >1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine-mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31-q42 and 11q14-q24

Genomewide scan identifies susceptibility locus for dyslexia on Xq27 in an extended Dutch family.

CONTEXT: Dyslexia is a common disorder with a strong genetic component, but despite significant research effort, the aetiology is still largely unknown. OBJECTIVE: To identify loci contributing to dyslexia risk. METHODS: This was a genomewide linkage analysis in a single large family. Dutch families with at least two first degree relatives suffering from dyslexia participated in the study. Participants were recruited through an advertisement campaign in papers and magazines. The main outcome measure was linkage between genetic markers and dyslexia phenotype. RESULTS: Using parametric linkage analysis, we found strong evidence for a locus influencing dyslexia on Xq27.3 (multipoint lod = 3.68). Recombinations in two family members flanked an 8 cM region, comprising 11 currently confirmed genes. All four males carrying the risk haplotype had very low scores on the reading tests. The presentation in females was more variable, but 8/9 females carrying the risk haplotype were diagnosed dyslexic by our composite score, so we considered the putative risk allele to be dominant with reduced penetrance. Linkage was not found in an additional collection of affected sibling pairs. CONCLUSIONS: A locus influencing dyslexia risk is probably located between markers DXS1227 and DXS8091 on the X chromosome, closely situated to a locus indicated by a published genome scan of English sibling pairs. Although the locus may not be a common cause for dyslexia, the relatively small and gene poor region offers hope to identify the responsible gene