Browsing by Subject "Mosaicism"

Now showing 1 - 3 of 3

Open Access
A Genetic Mosaic Screen Reveals Ecdysone-Responsive Genes Regulating Drosophila Oogenesis.
(G3 (Bethesda, Md.), 2016-08) Ables, Elizabeth T; Hwang, Grace H; Finger, Danielle S; Hinnant, Taylor D; Drummond-Barbosa, Daniela
Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets. More recently, genome-wide approaches have identified hundreds of putative ecdysone-responsive targets. Determining whether these putative targets represent bona fide targets in vivo, however, requires that they be tested via traditional mutant analysis in a cell-type specific fashion. To investigate the molecular mechanisms whereby ecdysone signaling regulates oogenesis, we used genetic mosaic analysis to screen putative ecdysone-responsive genes for novel roles in the control of the earliest steps of oogenesis. We identified a cohort of genes required for stem cell maintenance, stem and progenitor cell proliferation, and follicle encapsulation, growth, and survival. These genes encode transcription factors, chromatin modulators, and factors required for RNA transport, stability, and ribosome biogenesis, suggesting that ecdysone might control a wide range of molecular processes during oogenesis. Our results suggest that, although ecdysone target genes are known to have cell type-specific roles, many ecdysone response genes that control larval or pupal cell types at developmental transitions are used reiteratively in the adult ovary. These results provide novel insights into the molecular mechanisms by which ecdysone signaling controls oogenesis, laying new ground for future studies.
Open Access
Behavior genetics and postgenomics.
(Behav Brain Sci, 2012-10) Charney, Evan
The science of genetics is undergoing a paradigm shift. Recent discoveries, including the activity of retrotransposons, the extent of copy number variations, somatic and chromosomal mosaicism, and the nature of the epigenome as a regulator of DNA expressivity, are challenging a series of dogmas concerning the nature of the genome and the relationship between genotype and phenotype. According to three widely held dogmas, DNA is the unchanging template of heredity, is identical in all the cells and tissues of the body, and is the sole agent of inheritance. Rather than being an unchanging template, DNA appears subject to a good deal of environmentally induced change. Instead of identical DNA in all the cells of the body, somatic mosaicism appears to be the normal human condition. And DNA can no longer be considered the sole agent of inheritance. We now know that the epigenome, which regulates gene expressivity, can be inherited via the germline. These developments are particularly significant for behavior genetics for at least three reasons: First, epigenetic regulation, DNA variability, and somatic mosaicism appear to be particularly prevalent in the human brain and probably are involved in much of human behavior; second, they have important implications for the validity of heritability and gene association studies, the methodologies that largely define the discipline of behavior genetics; and third, they appear to play a critical role in development during the perinatal period and, in particular, in enabling phenotypic plasticity in offspring. I examine one of the central claims to emerge from the use of heritability studies in the behavioral sciences, the principle of minimal shared maternal effects, in light of the growing awareness that the maternal perinatal environment is a critical venue for the exercise of adaptive phenotypic plasticity. This consideration has important implications for both developmental and evolutionary biology.
Open Access
Detectable clonal mosaicism from birth to old age and its relationship to cancer.
(Nature genetics, 2012-05-06) Laurie, Cathy C; Laurie, Cecelia A; Rice, Kenneth; Doheny, Kimberly F; Zelnick, Leila R; McHugh, Caitlin P; Ling, Hua; Hetrick, Kurt N; Pugh, Elizabeth W; Amos, Chris; Wei, Qingyi; Wang, Li-e; Lee, Jeffrey E; Barnes, Kathleen C; Hansel, Nadia N; Mathias, Rasika; Daley, Denise; Beaty, Terri H; Scott, Alan F; Ruczinski, Ingo; Scharpf, Rob B; Bierut, Laura J; Hartz, Sarah M; Landi, Maria Teresa; Freedman, Neal D; Goldin, Lynn R; Ginsburg, David; Li, Jun; Desch, Karl C; Strom, Sara S; Blot, William J; Signorello, Lisa B; Ingles, Sue A; Chanock, Stephen J; Berndt, Sonja I; Le Marchand, Loic; Henderson, Brian E; Monroe, Kristine R; Heit, John A; de Andrade, Mariza; Armasu, Sebastian M; Regnier, Cynthia; Lowe, William L; Hayes, M Geoffrey; Marazita, Mary L; Feingold, Eleanor; Murray, Jeffrey C; Melbye, Mads; Feenstra, Bjarke; Kang, Jae H; Wiggs, Janey L; Jarvik, Gail P; McDavid, Andrew N; Seshan, Venkatraman E; Mirel, Daniel B; Crenshaw, Andrew; Sharopova, Nataliya; Wise, Anastasia; Shen, Jess; Crosslin, David R; Levine, David M; Zheng, Xiuwen; Udren, Jenna I; Bennett, Siiri; Nelson, Sarah C; Gogarten, Stephanie M; Conomos, Matthew P; Heagerty, Patrick; Manolio, Teri; Pasquale, Louis R; Haiman, Christopher A; Caporaso, Neil; Weir, Bruce S
We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).