RESUMEN
Natural variation in the absolute and relative size of different parts of the human brain is substantial, with a range that often exceeds a factor of 2. Much of this variation is generated by the cumulative effects of sets of unknown gene variants that modulate the proliferation, growth and death of neurons and glial cells. Discovering and testing the functions of these genes should contribute significantly to our understanding of differences in brain development, behavior and disease susceptibility. We have exploited a large population of genetically well-characterized strains of mice (BXD recombinant inbred strains) to map gene variants that influence the volume of the dorsal striatum (caudate-putamen without nucleus accumbens). We used unbiased methods to estimate volumes bilaterally in a sex-balanced sample taken from the Mouse Brain Library (www.mbl.org). We generated a matched microarray data set to efficiently evaluate candidate genes (www.genenetwork.org). As in humans, volume of the striatum is highly heritable, with greater than twofold differences among strains. We mapped a locus that modulates striatal volume on chromosome (Chr) 6 at 88 +/- 5 Mb. We also uncovered an epistatic interaction between loci on Chr 6 and Chr 17 that modulates striatal volume. Using bioinformatic tools and the corresponding expression database, we have identified positional candidates in these quantitative trait locus intervals.
Asunto(s)
Cuerpo Estriado/anatomía & histología , Variación Genética/genética , Animales , Mapeo Cromosómico/métodos , Cromosomas de los Mamíferos/genética , Biología Computacional/métodos , Cuerpo Estriado/citología , Cuerpo Estriado/metabolismo , Cruzamientos Genéticos , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica/métodos , Regulación del Desarrollo de la Expresión Génica , Genotipo , Masculino , Ratones , Ratones Endogámicos , Neurogénesis/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Tamaño de los Órganos/genética , Fenotipo , Sitios de Carácter Cuantitativo/genética , Especificidad de la EspecieRESUMEN
The purpose of this study was to examine students' conception of their learning in a problem-based learning medical curriculum. A multiple case study design was used with two units of analyses: two PBL lab groups; and 15 individual students within each lab group. Data collected included weekly journals by students, video-tapes of PBL sessions, focus group interviews with students, two open-ended questionnaires completed by students, and interviews with the PBL tutors. Three thematic categories of students' conceptions of their learning emerged: (1) awareness of PBL goals and expectations; (2) efficiency and expertise; and (3) the role of the tutor.