RESUMO
We studied two candidate genes, tau (tau) and alpha-synuclein (SNCA), for evidence of linkage disequilibrium on a group of unrelated individuals with progressive supranuclear palsy (PSP) and a group of age-matched control subjects. The tau alpha1 allele and the tau alpha1alpha1 genotype were overrepresented in individuals with PSP and the tau polymorphism was in linkage disequilibrium with the PSP disease locus when a recessive inheritance model was employed. We also report a lack of evidence to support linkage disequilibrium between PSP and the SNCA candidate Parkinson's disease gene on chromosome 4q21-q23.
Assuntos
Cromossomos Humanos Par 4 , Ligação Genética , Proteínas do Tecido Nervoso/genética , Paralisia Supranuclear Progressiva/genética , Proteínas tau/genética , Idoso , Alelos , Haplótipos , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Sinucleínas , alfa-SinucleínaRESUMO
We report the results of linkage analysis in a large American family of Czech descent with dominantly inherited "pure" essential tremor (ET) and genetic anticipation. Genetic loci on chromosome 2p22-p25 establish linkage to this region with a maximum LOD score (Zmax) = 5.92 for the locus, D2S272. Obligate recombinant events place the ETM gene in a 15-cM candidate interval between the genetic loci D2S168 and D2S224. Repeat expansion detection analysis suggests that expanded CAG trinucleotide sequences are associated with ET. These findings will facilitate the search for an ETM gene and may further our understanding of the human motor system.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos Par 2/genética , Tremor/genética , Adolescente , Adulto , Idoso , Criança , Transtornos Cromossômicos , República Tcheca/etnologia , Ligação Genética/genética , Haplótipos/genética , Humanos , Pessoa de Meia-Idade , Linhagem , Fenótipo , Índice de Gravidade de Doença , Tremor/diagnóstico , Repetições de Trinucleotídeos/genética , Estados Unidos , Cromossomo XRESUMO
The autosomal dominant ataxias (ADA) are a diverse group of multisystem, neurodegenerative disorders characterized by mutations at several chromosomal loci (SCA types 1-5, SCA type 7, DRPLA). We excluded all the known SCA loci by mutational and linkage analyses is an American family of British origin with ADA and document that an additional ataxia locus must exist. The clinical characteristics and ethnic origin of our family are similar to the British Drew family of Walworth with the SCA type 3 mutation and differ from other families without a known ataxia locus. Individuals in our family and the Drew family initially show signs of ataxia but may develop variable degrees of ophthalmoplegia, Parkinsonian features and central demyelination. The phenotypic diversity in families without a known ataxia locus suggests that there may be several other undefined ataxia loci.
Assuntos
Degenerações Espinocerebelares/genética , Adolescente , Adulto , Encéfalo/patologia , Aberrações Cromossômicas , Transtornos Cromossômicos , Primers do DNA , Doenças Desmielinizantes , Feminino , Amplificação de Genes , Ligação Genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fenótipo , Mutação Puntual , Reação em Cadeia da Polimerase , Degenerações Espinocerebelares/patologiaRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 4 , Doença de Parkinson/genética , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Linhagem , FenótipoRESUMO
Entamoeba histolytica genomic organization and putative promoter elements appear to be distinct from both metazoan and better characterized protozoan organisms. The recent development of DNA-mediated transfection for E. histolytica enabled characterization of cis-acting promoter elements required for gene expression. A deletion and replacement analysis was conducted on the promoter of an E. histolytica gene encoding the heavy subunit of the N-acetyl-beta-D-galactosamine-specific adhesin (hgl5). Deletion of the DNA from -1000 bases to -272 bases upstream from the start of transcription of hgl5 did not decrease reporter gene expression. Subsequent nested deletions and 10-bp replacement mutagenesis identified four positive upstream regulatory elements between bases -219 to -200, -189 to -160, -69 to -60, and -49 to -40. A negative upstream regulatory element between bases -89 to -80 was conserved upstream of three other E. histolytica genes. Mutation of the previously unidentified 'GAAC' element conserved within the putative core promoter decreased reporter gene expression by 75%. Site directed mutagenesis of the putative TATA element decreased reporter gene expression by greater than 50%, while mutation of the putative initiator element resulted in a more modest decrease. This analysis suggests that E. histolytica promoters are unlike other protozoan promoters, with AT-rich upstream regulatory elements, a non-consensus TATA element, the "GAAC' element, and an unusual initiator element.
Assuntos
Entamoeba histolytica/genética , Genes de Protozoários , Lectinas/genética , Glicoproteínas de Membrana/genética , Proteínas de Protozoários/genética , Animais , Sequência de Bases , Sequência Conservada , Primers do DNA/genética , DNA de Protozoário/genética , Regulação da Expressão Gênica , Genes Reguladores , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA de Protozoário/genética , TransfecçãoRESUMO
Development of DNA-mediated transfection in Entamoeba histolytica will facilitate basic research toward the control of this protozoan parasite. A transient transfection system was established by using the firefly luciferase gene ligated to the 5' and 3' flanking regions of the amebic hgl1 gene. The optimal construct tested encoded an hgl1-luciferase fusion protein and contained 1 kb of 5' flanking sequence with 16 bases of coding sequence from the hgl1 gene ligated in-frame to the luciferase start codon and 2.3 kb of 3' flanking sequence from hgl1 ligated 3' to the luciferase stop codon. Optimal electroporation conditions in strain HM-1:IMSS trophozoites when using this construct were 500 microF and 500 V/cm, which resulted in luciferase activity up to 5000-fold above background 9-12 hr after electroporation. Constructs that contained the luciferase gene without amebic flanking sequences or that contained a simian virus 40 promoter, enhancer, and polyadenylylation signal produced only background levels of luciferase activity. The ability to introduce and express genes in amebae will now permit a genetic analysis of the virulence of this organism, which remains a serious threat to world health.