Assuntos
Predisposição Genética para Doença/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos/genética , Caderinas/genética , Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 9/genética , Quinase 4 Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p15 , Inibidor p16 de Quinase Dependente de Ciclina/química , Inibidor p16 de Quinase Dependente de Ciclina/genética , Quinases Ciclina-Dependentes/genética , Feminino , Genes BRCA2 , Genes Neoplásicos/genética , Ligação Genética/genética , Humanos , Itália , Masculino , Melanoma/diagnóstico , Melanoma/enzimologia , Pessoa de Meia-Idade , Modelos Moleculares , Linhagem , Proteínas Proto-Oncogênicas/genética , Proteína Supressora de Tumor p14ARF/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Multiple sclerosis (MS), an inflammatory autoimmune demyelinating disorder of the central nervous system, is the most common cause of acquired neurological dysfunction arising in the second to fourth decades of life. A genetic component to MS is indicated by an increased relative risk of 20-40 to siblings compared to the general population (lambda s), and an increased concordance rate in monozygotic compared to dizygotic twins. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatability complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci. With the exception of the MHC, however, these results have been difficult to replicate and/or apply beyond isolated populations. We have therefore conducted a two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes. We genotyped 443 markers and 19 such regions were identified. These included the MHC region on 6p, the only region with a consistently reported genetic effect. However, no single locus generated overwhelming evidence of linkage. Our results suggest that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than an aetiology consisting of simple mendelian disease gene(s).
Assuntos
Cromossomos Humanos Par 6 , Complexo Principal de Histocompatibilidade , Esclerose Múltipla/genética , Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 7/genética , Ligação Genética , Marcadores Genéticos , Humanos , LinhagemRESUMO
The loci for the juvenile (CLN3) and infantile (CLN1) neuronal ceroid lipofuscinosis (NCL) types have been mapped by genetic linkage analysis to chromosome arms 16p and 1p, respectively. The late-infantile defect CLN2 has not yet been mapped, although linkage analysis with tightly linked markers excludes it from both the JNCL and INCL loci. We have initiated a genome-wide search for the LNCL gene, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 US families and 11 Costa Rican families. To date, we have completed typing with over 50 markers on chromosomes 2, 9, 13, and 18-22. The results of this analysis formally exclude about 10% of the human genome as the location of the LNCL gene.