The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Olga Amaral - One of the best experts on this subject based on the ideXlab platform.
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Unverricht–Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene
Epilepsy Research, 2011Co-Authors: Eugénia Pinto, Joel Freitas, Ana Joana Duarte, Isaura Ribeiro, Diogo Ribeiro, J. Lopes Lima, João Chaves, Olga AmaralAbstract:Summary Unverricht–Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in Homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of Homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB .
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Unverricht-Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene.
Epilepsy research, 2011Co-Authors: Eugénia Pinto, Joel Freitas, Ana Joana Duarte, Isaura Ribeiro, Diogo Ribeiro, J. Lopes Lima, João Chaves, Olga AmaralAbstract:Unverricht-Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in Homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of Homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB.
Mike A Nalls - One of the best experts on this subject based on the ideXlab platform.
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Homozygosity analysis in amyotrophic lateral sclerosis
European journal of human genetics : EJHG, 2013Co-Authors: Kin Y. Mok, Bryan J Traynor, Mike A Nalls, Hannu Laaksovirta, Pentti J. Tienari, Terhi Peuralinna, Liisa Myllykangas, Adriano Chiò, Nicole Gurunlian, Aleksey ShatunovAbstract:Amyotrophic lateral sclerosis (ALS) may appear to be familial or sporadic, with recognised dominant and recessive inheritance in a proportion of cases. Sporadic ALS may be caused by rare homozygous recessive mutations. We studied patients and controls from the UK and a multinational pooled analysis of GWAS data on Homozygosity in ALS to determine any potential recessive variant leading to the disease. Six-hundred and twenty ALS and 5169 controls were studied in the UK cohort. A total of 7646 Homozygosity segments with length >2 Mb were identified, and 3568 rare segments remained after filtering 'common' segments. The mean total of the autosomal genome with Homozygosity segments was longer in ALS than in controls (unfiltered segments, P=0.05). Two-thousand and seventeen ALS and 6918 controls were studied in the pooled analysis. There were more regions of Homozygosity segments per case (P=1 × 10(-5)), a greater proportion of cases harboured Homozygosity (P=2 × 10(-5)), a longer average length of segment (P=1 × 10(-5)), a longer total genome coverage (P=1 × 10(-5)), and a higher rate of these segments overlapped with RefSeq gene regions (P=1 × 10(-5)), in ALS patients than controls. Positive associations were found in three regions. The most significant was in the chromosome 21 SOD1 region, and also chromosome 1 2.9-4.8 Mb, and chromosome 5 in the 65 Mb region. There are more than twenty potential genes in these regions. These findings point to further possible rare recessive genetic causes of ALS, which are not identified as common variants in GWAS.
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Cooperative genome-wide analysis shows increased Homozygosity in early onset Parkinson's disease.
PloS one, 2012Co-Authors: J. Simon-sanchez, Mike A Nalls, Laura L. Kilarski, Maria Martinez, Claudia Schulte, Peter Holmans, Thomas Gasser, John Hardy, Andrew B. Singleton, Nicholas W. WoodAbstract:Parkinson's disease (PD) occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of Homozygosity. We carried out genome wide SNP genotyping to look for extended runs of Homozygosity (ROHs) in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic Homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide Homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort. There is an increased rate of genome wide Homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis.
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Extended tracts of Homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease
neurogenetics, 2009Co-Authors: Mike A Nalls, R. J. Guerreiro, J. Simon-sanchez, J. T. Bras, J. R. Gibbs, L. Launer, Bryan J Traynor, J. Hardy, A B SingletonAbstract:Large tracts of extended Homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended Homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended Homozygosity (greater than 1 Mb in length) in a population of 837 late-onset Alzheimer’s disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR , EIF4EBP1 , and ADRB3 . We also compared the total numbers of homozygous runs and the total length of these runs between cases and controls, showing a suggestive difference in these measures ( p -values 0.052–0.062). This research suggests a recessive component to the etiology of LOAD.
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extended tracts of Homozygosity identify novel candidate genes associated with late onset alzheimer s disease
Neurogenetics, 2009Co-Authors: Mike A Nalls, J. R. Gibbs, Bryan J Traynor, Rita Guerreiro, Javier Simonsanchez, Jose Bras, Lenore J Launer, John HardyAbstract:Large tracts of extended Homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended Homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended Homozygosity (greater than 1 Mb in length) in a population of 837 late-onset Alzheimer's disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR, EIF4EBP1, and ADRB3. We also compared the total numbers of homozygous runs and the total length of these runs between cases and controls, showing a suggestive difference in these measures (p-values 0.052-0.062). This research suggests a recessive component to the etiology of LOAD.
Eugénia Pinto - One of the best experts on this subject based on the ideXlab platform.
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Unverricht–Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene
Epilepsy Research, 2011Co-Authors: Eugénia Pinto, Joel Freitas, Ana Joana Duarte, Isaura Ribeiro, Diogo Ribeiro, J. Lopes Lima, João Chaves, Olga AmaralAbstract:Summary Unverricht–Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in Homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of Homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB .
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Unverricht-Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene.
Epilepsy research, 2011Co-Authors: Eugénia Pinto, Joel Freitas, Ana Joana Duarte, Isaura Ribeiro, Diogo Ribeiro, J. Lopes Lima, João Chaves, Olga AmaralAbstract:Unverricht-Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in Homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of Homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB.
Jaspreet Singh Pahwa - One of the best experts on this subject based on the ideXlab platform.
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No evidence that extended tracts of Homozygosity are associated with Alzheimer's disease
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2011Co-Authors: Rebecca Sims, Sarah Dwyer, Denise Harold, Amy Gerrish, Paul Hollingworth, Jade Chapman, Nicola Jones, Richard Abraham, Dobril Ivanov, Jaspreet Singh PahwaAbstract:We sought to investigate the contribution of extended runs of Homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of Homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of Homozygosity showed association to Alzheimer's disease.
Joel Freitas - One of the best experts on this subject based on the ideXlab platform.
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Unverricht–Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene
Epilepsy Research, 2011Co-Authors: Eugénia Pinto, Joel Freitas, Ana Joana Duarte, Isaura Ribeiro, Diogo Ribeiro, J. Lopes Lima, João Chaves, Olga AmaralAbstract:Summary Unverricht–Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in Homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of Homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB .
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Unverricht-Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene.
Epilepsy research, 2011Co-Authors: Eugénia Pinto, Joel Freitas, Ana Joana Duarte, Isaura Ribeiro, Diogo Ribeiro, J. Lopes Lima, João Chaves, Olga AmaralAbstract:Unverricht-Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in Homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of Homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB.