 |
Forthcoming events (seminars, conferences etc.)
26.10.2011 (Wednesday), 16:00-17:00, IMCS, room 210
Dace Ruklisa
Association Studies for Early Developmental Phenotypes in Drosophila melanogaster
Abstract
Oocyte development in Drosophila melanogaster is an interesting model of
developmental processes and their timing, especially when localization of
crucial components, formation of dorsal-ventral axis and segmentation is
considered. Early development in fruit fly is has been previously studied
by qualitative means thus highlighting many important pathways of mRNA and
protein localization. Severe mutations usually get the most of attention,
like mislocalization patterns leading to a failure to hatch for an embryo.
I attempted to characterize developmental patterns during oogenesis as
continuously varying traits. Such an approach is more precise in
identification of subtle variation in development and is suitable for
performing association study using isogenic population, which typically
does not contain severe mutations for any particular trait.
The quantitative characterization of fruit fly development requires
deciding upon the method of the phenotype collection and then upon the
approach towards phenotype measurement. A novel approach towards defining
developmental traits is proposed, which is based on the optical microscopy
techniques and a pipeline of image analysis algorithms. Traits were scored
from microscope images highlighting the crucial components of oocyte
during various developmental stages. A set of suitable metrics for the
quantitative characterization of a phenotype is suggested, most of them
based on rotationally invariant image moments, for instance Zernike
moments, and others describing geometric features and texture.
Oogenesis traits were further subjected to the genome wide association
study. This study is among the first ones to exploit roughly 6 million
different loci for Drosophila melanogaster.
Association study yielded 5 candidate loci for 5 different traits. Most of
the associated phenotypes characterize the distribution of DNA within
nurse cell nuclei, apart from the cell compactness. The majority of loci
discovered either directly hit or are nearby important developmental
genes. Most of the associated loci are located within introns and none
belongs to a coding region. Thus the variants discovered might participate
in regulating the level of gene expression. This hypothesis was confirmed
by the information from modENCODE indicating that most of the associated
SNPs belong to a binding site and are marked as upstream or downstream.