RESUMEN
We present the findings of a linkage study of bipolar affective disorder (BPAD) that involve the pseudoautosomal region 1 of the human sex chromosomes. We analyzed a substantial subset of pedigrees (89 families of German and Spanish origin; 661 participants; 298 affected individuals) from the large collection of BPAD-affected families with which a genomewide linkage analysis was previously performed and where the pseudoautosomal regions were poorly covered. Nonparametric linkage (Z(lr)) scores were calculated. The highest Z(lr) scores were obtained on Xp22.3/Yp11.3 in the Spanish subsample (DXS1071; Z(lr) = 3.54, P(empirical) = 0.0009 for the broad definition of affection sttuts; Z(lr) = 2.63, P(empirical) = 0.0129 for the medium definition of affection status; Z(lr) = 2.12, P(empirical) = 0.0429 for the narrow definition of affection status). Empirical P-values are adjusted using the Bonferroni correction to account for the testing of three affection status definitions. This region has not drawn much attention in previous linkage studies of BPAD. On the basis of these results, Xp22.3/Yp11.3 should now be considered a candidate region for BPAD.
Asunto(s)
Trastorno Bipolar/genética , Cromosomas Humanos X/genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad , Femenino , Ligamiento Genético , Humanos , MasculinoRESUMEN
We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German families (280 individuals) was included for this fine-mapping step. The highest nonparametric linkage scores obtained in the fine mapping were 5.49 for 4q31 and 4.87 for 6q24 in the Romany families and 3.97 for 1p35-p36 in the Spanish sample. MOD-score (LOD scores maximized over genetic model parameters) analysis provided significant evidence of linkage to 4q31 and at least borderline significance for the 1p and 6q regions. On the basis of these results and previous positive research findings, 4q31 and 6q24 should now be considered confirmed BPAD susceptibility loci, and 1p35-p36 is proposed as a new putative locus that requires confirmation in replication studies.
Asunto(s)
Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 4/genética , Cromosomas Humanos Par 6/genética , Predisposición Genética a la Enfermedad , Genoma Humano , Mapeo Físico de Cromosoma , Trastorno Bipolar/genética , Bulgaria/etnología , Marcadores Genéticos , Alemania/etnología , Humanos , Escala de Lod , Romaní/etnología , España/etnología , Población Blanca/etnología , Población Blanca/estadística & datos numéricosRESUMEN
Se estudiaron 59 familiares de pacientes con Ataxia Cerebelosa Dominante Cubana (SCA2) durante diez años. A todos se les realizó un examen físico para valorar su estado clínico y estudios de conducción en nervios periféricos motores y sensitivos. En 13 de ellos se encontraron manifestaciones clínicas de la enfermedad. En otros 11 familiares se detectaron alteraciones electrofisiológicas en ausencia de síntomas y signos de SCA2. La principal alteración electrofisiológica encontrada fue la reducción en la aplitud de los potenciales sensitivos, lo que es expresión de una lesión axonal que se presenta desde etapas presintomáticas.