RESUMO
We report on a genome-wide screen for association with multiple sclerosis (MS) in the German population performed using 6000 microsatellite markers. These markers were typed in four DNA pools consisting of 234 MS patients (cases), 209 unrelated controls, 68 index patients from trio families and their 136 parents (related controls). Stringent analysis identified 11 markers showing apparent evidence for association. Five from regions previously identified in linkage studies and two from the MHC region on chromosome 6p21. These MHC markers are known to be in linkage disequilibrium with HLA class II alleles influencing susceptibility to MS. The identification of these markers serves as an important positive control.
Assuntos
Testes Genéticos/métodos , Genoma Humano , Desequilíbrio de Ligação , Esclerose Múltipla/genética , Adulto , Alelos , Feminino , Frequência do Gene , Alemanha/epidemiologia , Humanos , Cooperação Internacional , Masculino , Repetições de Microssatélites , Esclerose Múltipla/epidemiologiaRESUMO
Although the pathogenesis of multiple sclerosis (MS) is not fully understood, substantial evidence points to the involvement of genetic factors. We report on a genome-wide screen for disease association in the Hungarian population using 5532 microsatellite markers. These markers were typed in DNA pools that consisted of 88 MS patients (cases), and 128 unrelated controls. Based on a stringent selection criterion, we obtained 33 markers suggesting association with the disease.
Assuntos
Predisposição Genética para Doença , Testes Genéticos/métodos , Genoma Humano , Adulto , Estudos de Casos e Controles , Feminino , Testes Genéticos/estatística & dados numéricos , Genótipo , Humanos , Hungria/epidemiologia , Cooperação Internacional , Masculino , Repetições de Microssatélites , Reação em Cadeia da Polimerase , SoftwareRESUMO
We have performed the first systematic search for MS susceptibility genes completed in the Polish population. This screen was performed using 6000 microsatellite markers typed in pooled DNA from cases (n=200), controls (n=200) and trio families (n=129). Five associated markers are identified, one (D6S2444) from the HLA region and four are from novel regions not previously associated with MS, 2p16 (D2S2153), 3p13 (D3S3568), 7p22 (D7S2521) and 15q26 (D15S649).
Assuntos
Predisposição Genética para Doença , Testes Genéticos/métodos , Genoma Humano , Esclerose Múltipla/genética , Adulto , Estudos de Casos e Controles , DNA/sangue , Eletroforese Capilar , Feminino , Testes Genéticos/estatística & dados numéricos , Genótipo , Humanos , Desequilíbrio de Ligação/genética , Masculino , Repetições de Microssatélites , Esclerose Múltipla/epidemiologia , Polônia/epidemiologia , Reação em Cadeia da Polimerase/estatística & dados numéricosRESUMO
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) with a complex genetic background. Here we use a genome-wide association strategy with 4804 microsatellite markers successfully typed in separately pooled DNA from 200 patients and 200 controls. A total of 91 markers showed evidence of association. When compared to our in-house physical map of the genome, six 2-Mb regions containing at least two of these markers were detected. Of those, three regions have one or more markers among the 20 most strongly associated: chromosomes 3q25, 6p21.3 (the MHC region) and 19q13.
Assuntos
Testes Genéticos/métodos , Genoma Humano , Repetições de Microssatélites , Esclerose Múltipla/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Testes Genéticos/estatística & dados numéricos , Genótipo , Humanos , Islândia/epidemiologia , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologiaRESUMO
Genetic factors are known to influence susceptibility to multiple sclerosis (MS) but the genes involved are largely undefined. Here, we report an association study based on 200 patients and 200 controls from the Porto region in Portugal. A total of 3974 markers were successfully typed from which we have identified 46 markers showing evidence of association. When compared to a physical map three regions were found with two of these markers less than 1.5 Mb apart: chromosomes 6p21.3 (the MHC region), 6q14.1 and 7q34.
Assuntos
Predisposição Genética para Doença , Testes Genéticos/métodos , Genoma Humano , Esclerose Múltipla/genética , Adolescente , Idoso , Estudos de Casos e Controles , DNA/sangue , Eletroforese Capilar , Feminino , Testes Genéticos/estatística & dados numéricos , Genética Populacional , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Reação em Cadeia da Polimerase , Portugal/epidemiologiaRESUMO
In order to identify the genomic regions that might confer susceptibility to multiple sclerosis (MS) in the Spanish population, we have performed a genome-wide screen for association in patients with MS using pooled DNA from 200 clinical cases and 200 healthy controls. The pools were typed using 5546 microsatellites. The typing was repeated for the most promising 1269 markers after which 191 potentially associated markers were identified. Eleven of these markers map to the MHC region, and 14 to non-MHC regions identified in previous linkage screens. Our results provide support for the presence of multiple coding regions that contain MS susceptibility genes of small or moderate effect.