Re-evaluating the driving force behind mutations.

Experiments on tropical trees suggest that new mutations in plants are driven by age rather than number of cell divisions during growth.

CRISPR-Cas9 Mediated Genome Editing in Drosophila.

In recent years, great progress has been made in the research of genome editing systems, one of which is the CRISPR-Cas9 system, a powerful technology that is applied to edit animal genome. Here, we describe a CRISPR-Cas9 mediated mutation protocol for efficiently and specifically editing genes in Drosophila. In this optimized system, the mutant progeny can be generated by only injecting a DNA plasmid encoding synthetic guide RNA (sgRNA) under the control of the U6b promoter into transgenic fly embryos in which Cas9 is specifically expressed in the progenitor cells, thus the gene of interest can be edited by the CRISPR in germ cells, with high rate of heritable mutations and few side effects.

Discovering human germ cell mutagens with whole genome sequencing: Insights from power calculations reveal the importance of controlling for between-family variability.

Mutations in germ cells pose potential genetic risks to offspring. However, de novo mutations are rare events that are spread across the genome and are difficult to detect. Thus, studies in this area have generally been under-powered, and no human germ cell mutagen has been identified. Whole Genome Sequencing (WGS) of human pedigrees has been proposed as an approach to overcome these technical and statistical challenges. WGS enables analysis of a much wider breadth of the genome than traditional approaches. Here, we performed power analyses to determine the feasibility of using WGS in human families to identify germ cell mutagens. Different statistical models were compared in the power analyses (ANOVA and multiple regression for one-child families, and mixed effect model sampling between two to four siblings per family). Assumptions were made based on parameters from the existing literature, such as the mutation-by-paternal age effect. We explored two scenarios: a constant effect due to an exposure that occurred in the past, and an accumulating effect where the exposure is continuing. Our analysis revealed the importance of modeling inter-family variability of the mutation-by-paternal age effect. Statistical power was improved by models accounting for the family-to-family variability. Our power analyses suggest that sufficient statistical power can be attained with 4-28 four-sibling families per treatment group, when the increase in mutations ranges from 40 to 10% respectively. Modeling family variability using mixed effect models provided a reduction in sample size compared to a multiple regression approach. Much larger sample sizes were required to detect an interaction effect between environmental exposures and paternal age. These findings inform study design and statistical modeling approaches to improve power and reduce sequencing costs for future studies in this area.

Cáncer de mama hereditario

El cáncer de mama ocurre cuando las células mamarias crecen sin control, debido a que éstas escapan de los exquisitos controles que regulan la multiplicación celular, ocasionando una proliferación celular sin respuesta a la regulación. La mayoría de los casos de cáncer de mama no tienen una causa identificable, pero aproximadamente del 5 al 10% son causados por mutaciones genéticas hereditarias. A pesar de que se conocen otros genes como causantes del cáncer de mama hereditario, la mayor parte de los estudios que evalúan las estrategias de manejo clínico se han centrado en mujeres con mutaciones en los genes BRCA1 o BRCA2 (BReast CAncer, por sus siglas en inglés). Los individuos portadores de mutaciones en estos genes tienen un aumento significativo del riesgo a lo largo de su vida de padecer esta patología, comparado con el riesgo de la población general.

Breast cancer occurs when breast cells grow out of control, because these exquisite escape controls that regulate cell proliferation, cell proliferation without causing a response to regulation. Most cases of breast cancer have no identifiable cause, but about 5 to 10% are caused by inherited genetic mutations. Although other genes as the cause of hereditary breast cancer, known most studies evaluating clinical management strategies have focused on women with mutations in BRCA1 or BRCA2 genes. Individuals carrying mutations in these genes have a significantly increased risk throughout his life of suffering this disease, compared to the risk of the general population.