Biomedical subjects

Pablo Serrano-Fernández

Publications and source records attributed to Pablo Serrano-Fernández.

8 recordsLinked to original sources

PubMed2006

MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk.

We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T.

Adult↗

PubMed2006

Definition of a 1.06-Mb region linked to neuroinflammation in humans, rats and mice.

Unbiased identification of susceptibility genes might provide new insights into pathogenic mechanisms that govern complex inflammatory diseases such as multiple sclerosis. In this study we fine mapped Eae18a, a region on rat chromosome 10 that regulates experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. We utilized two independent approaches: (1) in silico mapping based on sequence similarity between human multiple sclerosis susceptibility regions and rodent EAE quantitative trait loci and (2) linkage mapping in an F10 (DA x PVG.AV1) rat advanced intercrossed line. The linkage mapping defines Eae18a to a 5-Mb region, which overlaps one intergenomic consensus region identified in silico. The combined approach confirms experimentally, for the first time, the accuracy of the in silico method. Moreover, the shared intersection between the results of both mapping techniques defines a 1.06-Mb region containing 13 candidate genes for the regulation of neuroinflammation in humans, rats, and mice.

Animals↗

PubMed2006

Multiple sclerosis therapy monitoring based on gene expression.

Multiple sclerosis (MS) is the most prevalent chronic autoimmune, neurodegenerative disorder of the central nervous system (CNS). Despite substantial progress, treatment of MS and other autoimmune diseases is only moderately effective. It is anticipated that the treatment of autoimmune diseases with single drugs or biological approaches will in the future be complemented, or even replaced, by combination therapies, which include immunomodulation, elimination of infectious triggers and tissue repair. One proclaimed goal of biomedical research and clinical practice is the discovery of sets of genes with expression that correlates with successful outcomes of drug therapy, or with unfortunate side effects. Such information has direct consequences for selection, refinement or development of treatments and will soon be translated into clinical trials. The genome-wide RNA profile of an individual represents one complement to the comprehensive determination of disease- or drug response-related elements; comparable to a 'sentinel' method, it serves as a large-scale approach to MS biology. This work reviews the state of the art in MS research at the transcriptome level applying genomewide screening methods. It discusses implications in understanding disease pathogenicity, diagnostic markers, the identification of new therapeutic targets and a classification of patients towards the advent of tailored therapies.

Biomarkers↗

PubMed2006

Comparative genomics for the investigation of autoimmune diseases.

The complete DNA sequence of the human genome and of several related mammals are now available, due to the investments of enormous resources and advances in sequencing technology. Novel technologies have been developed to compare multiple genomes with each other, thus specifying regions of sequence similarity among mammals and with their pathogens. Larger blocks of sequence similarity (syntenic regions) have been determined and made publicly available. In many ways, novel insights can be gained by such data when combining external genetic or clinical information for these syntenic loci. These novel tools have proven to be successful in inferring functional equivalence between loci of multiple genomes. This review reports on the role of comparative genomics in research on autoimmune diseases, a field with strong dependencies on animal models of human diseases and the problem of an adequate information transfer between multiple organisms and research areas.

Animals↗

PubMed2005

Collection of soluble variants of membrane proteins for transcriptomics and proteomics.

The existence of a soluble splice variant for a gene encoding a transmembrane protein suggests that this gene plays a role in intercellular signalling, particularly in immunological processes. Also, the absence of a splice variant of a reported soluble variant suggests exclusive control of the solubilisation by proteolytic cleavage. Soluble splice variants of membrane proteins may also be interesting targets for crystallisation as their structure may be expected to preserve, at least partially, their function as integral membrane proteins, whose structures are most difficult to determine. This paper presents a dataset derived from the literature in an attempt to collect all reported soluble variants of membrane proteins, be they splice variants or shedded. A list of soluble variants is derived in silico from Ensembl. These are checked on their presence in multiple organisms and their number of membranespanning regions is inspected. The findings then are confirmed by a comparison with identified proteins of a recent global proteomics study of human blood plasma. Finally, a tool to determine novel soluble variants by proteomics is provided.

Animals↗

PubMed2004

In silico fine-mapping: narrowing disease-associated loci by intergenomics.

UNLABELLED: Genetic linkage and association studies define quantitative trait loci (QTLs) and susceptibility loci (SLs) that influence the phenotype of polygenic traits. A web-accessible application was created to identify intergenomic consensuses to fine map QTLs and SLs in silico and select particularly promising candidate genes for such traits. Furthermore, this approach offers an empirical evaluation of animal models for their applicability to the study of human traits. AVAILABILITY: http://qtl.pzr.uni-rostock.de/qtlmix.php CONTACT: serrano@pzr.uni-rostock.de.

Animals↗

PubMed2004

Non-linear conversion between genetic and physical chromosomal distances.

UNLABELLED: A supervised nonlinear interpolation significantly improves the reliability of conversions from genetic distances to physical distances as compared with the linear ones. A webaccessible application was created that addresses this question with a graphical presentation that may be wrapped by local installations. MOTIVATION: Genetic linkage maps and radiation hybrid (RH) maps are based on the rate of uncoupling between linked genetic markers. These are usually measured in centiMorgan (cM) when uncoupling is originated by natural recombination or in centiRay (cR) for chromosomes that are irradiated artificially to separate the markers. Physical maps arise from genome-wide DNA sequencing and are measured in bp. This work was originally motivated as an extension of the software application Expressionview (Fischer et al., 2003), exploring its spectrum of appliance combining different mapping systems. The relationship between physical and genetic maps is known to be not always linear (Yu et al., 2001). The shift from the linear model seems to depend on local idiosyncrasies of the chromosomes and the kind of genetic map used. The present application addresses this problem for the first time. AVAILABILITY: http://qtl.pzr.uni-rostock.de/cartographer.php

Algorithms↗

PubMed2003

Expressionview: visualization of quantitative trait loci and gene-expression data in Ensembl.

We present here a software tool for combined visualization of gene-expression data and quantitative trait loci (QTL). The application is implemented as an extension to the Ensembl project and caters for a direct transition from microarray experiments of gene or protein expression levels to the genomic context of individual genes and QTL. It supports the visualization of gene clusters and the selection of functional candidate genes in the context of research on complex traits.

Animals↗