RESUMEN
This investigation was undertaken to assess the sensitivity and specificity of the genotyping error detection function of the computer program SIMWALK2. We chose to examine chromosome 22, which had 7 microsatellite markers, from a single simulated replicate (330 pedigrees with a pattern of missing genotype data similar to the Framingham families). We created genotype errors at five overall frequencies (0.0, 0.025, 0.050, 0.075, and 0.100) and applied SIMWALK2 to each of these five data sets, respectively assuming that the total error rate (specified in the program), was at each of these same five levels. In this data set, up to an assumed error rate of 10%, only 50% of the Mendelian-consistent mistypings were found under any level of true errors. And since as many as 70% of the errors detected were false-positives, blanking suspect genotypes (at any error probability) will result in a reduction of statistical power due to the concomitant blanking of correctly typed alleles. This work supports the conclusion that allowing for genotyping errors within likelihood calculations during statistical analysis may be preferable to choosing an arbitrary cut-off.
Asunto(s)
Programas Informáticos/estadística & datos numéricos , Programas Informáticos/normas , Hijos Adultos , Sesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Simulación por Computador/estadística & datos numéricos , Femenino , Genotipo , Humanos , Masculino , Núcleo Familiar , Linaje , Reproducibilidad de los ResultadosRESUMEN
We used molecular markers to study genetic relationships in a diverse collection of 85 domestic dog breeds. Differences among breeds accounted for approximately 30% of genetic variation. Microsatellite genotypes were used to correctly assign 99% of individual dogs to breeds. Phylogenetic analysis separated several breeds with ancient origins from the remaining breeds with modern European origins. We identified four genetic clusters, which predominantly contained breeds with similar geographic origin, morphology, or role in human activities. These results provide a genetic classification of dog breeds and will aid studies of the genetics of phenotypic breed differences.
Asunto(s)
Cruzamiento , Perros/genética , Variación Genética , Genoma , Repeticiones de Microsatélite , Algoritmos , Animales , Teorema de Bayes , Evolución Biológica , Biología Computacional , Enfermedades de los Perros/genética , Perros/clasificación , Genotipo , Fenotipo , Filogenia , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Programas InformáticosRESUMEN
Hereditary prostate cancer (HPC) is a genetically heterogeneous disease, complicating efforts to map and clone susceptibility loci. We have used stratification of a large dataset of 254 HPC families in an effort to improve power to detect HPC loci and to understand what types of family features may improve locus identification. The strongest result is that of a dominant locus at 6p22.3 (heterogeneity LOD (HLOD) = 2.51), the evidence for which is increased by consideration of the age of PC onset (HLOD = 3.43 in 214 families with median age-of-onset 56-72 years) and co-occurrence of primary brain cancer (HLOD = 2.34 in 21 families) in the families. Additional regions for which we observe modest evidence for linkage include chromosome 7q and 17p. Only weak evidence of several previously implicated HPC regions is detected. These analyses support the existence of multiple HPC loci, whose presence may be best identified by analyses of large, including pooled, datasets which consider locus heterogeneity.
Asunto(s)
Genoma Humano , Neoplasias de la Próstata/genética , Anciano , Neoplasias Encefálicas/genética , Neoplasias de la Mama/genética , ADN de Neoplasias/química , ADN de Neoplasias/genética , Familia , Femenino , Genes BRCA1 , Genes BRCA2 , Ligamiento Genético/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Neoplasias Ováricas/genética , Reacción en Cadena de la PolimerasaRESUMEN
The purebred dog population consists of >300 partially inbred genetic isolates or breeds. Restriction of gene flow between breeds, together with strong selection for traits, has led to the establishment of a unique resource for dissecting the genetic basis of simple and complex mammalian traits. Toward this end, we present a comprehensive radiation hybrid map of the canine genome composed of 3,270 markers including 1,596 microsatellite-based markers, 900 cloned gene sequences and ESTs, 668 canine-specific bacterial artificial chromosome (BAC) ends, and 106 sequence-tagged sites. The map was constructed by using the RHDF5000-2 whole-genome radiation hybrid panel and computed by using MULTIMAP and TSP/CONCORDE. The 3,270 markers map to 3,021 unique positions and define an average intermarker distance corresponding to 1 Mb. We also define a minimal screening set of 325 highly informative well spaced markers, to be used in the initiation of genome-wide scans. The well defined synteny between the dog and human genomes, established in part as a function of this work by the identification of 85 conserved fragments, will allow follow-up of initial findings of linkage by selection of candidate genes from the human genome sequence. This work continues to define the canine system as the method of choice in the pursuit of the genes causing mammalian variation and disease.