Gene Clustering Based on RNAi Phenotypes of Ovary-Enriched Genes in C. elegans

Abstract

Recently, a set of 766 genes that are enriched in the ovary as compared to the soma was identified by microarray analysis [1]. Here, we report a functional analysis of 98% of these genes by RNA interference (RNAi). Over half the genes tested showed at least one detectable phenotype, most commonly embryonic lethality, consistent with the expectation that ovary transcripts would be enriched for genes that are essential in basic cellular and developmental processes. We find that essential genes are more likely to be conserved and to be highly expressed in the ovary. We extend previous observations and find that fewer than the expected number of ovary-expressed essential genes are present on the X chromosome. We characterized early embryonic defects for 161 genes and used time-lapse microscopy to systematically describe the defects for each gene in terms of 47 RNAi-associated phenotypes. In this paper, we discuss the use of these data to group genes into "phenoclusters"; in the accompanying paper, we use these data as one component in the integration of different types of large-scale functional analyses. We find that phenoclusters correlate well with sequence-based functional predictions and thus may be useful in predicting functions of uncharacterized genes.

ATP-2 Interacts with the PLAT Domain of LOV-1 and Is Involved inCaenorhabditis elegansPolycystin Signaling

“…Column 2 indicates three-lettered italicized gene name and/or predicted protein product. Column 3 lists published RNAi phenotypes (Fraser et al, 2000;Gonczy et al, 2000b;Hanazawa et al, 2001;Kamath et al, 2003;Piano et al, 2002;Simmer et al, 2003). Phenotypic abbreviations: Bmb, body morphology defect; Clr, clear; Emb, embryonic lethal; Etv, embryonic terminal arrest variable; Gro, slow growth; Lva, larval lethal; Sma, small; Ste, sterile; Stp, sterile progeny; WT, wild type.…”

Profiling of gender-regulated gene transcripts in the filarial nematode Brugia malayi by cDNA oligonucleotide array analysis

“…Forty-seven percent (303/650) of the female up-regulated clusters had significant similarity to genes from C. elegans. Many of these C. elegans genes were highly expressed in embryos by microarray experiments [4], and 47% (112/237) of those studied by RNAi had phenotypes such as embryo lethality, growth defects and post-embryonic defects. Many of the annotated female upregulated clusters in our study were associated with embryonic development (fatty acid binding protein, chaperonin-like protein), eggshell formation (microfilaria sheath protein), factors involved in transcription and translation (RNA polymerase, tRNA-synthetase, ribosomal proteins), and energy supply (ATP synthase and enzymes in the citric acid cycle).…”

“…Basic research may identify new targets for intervention that interfere with egg, microfilaria, or sperm production [1,2]. Filariasis researchers stand to benefit from extensive functional genomic studies that have been performed on the free-living nematode Caenorhabditis elegans [3,4]. Since filarial parasites share many genes with C. elegans [5], information available on genes involved in reproduction in C. elegans is an important starting point for parallel studies in filarial worms [6].…”

Studying gene function in Caenorhabditis elegans using RNA-mediated interference

“…In a follow-up study, Piano etal. [36] evaluated a much larger set of ( 750) genes whose expression was described as ovary-enriched based on microarray analysis. This study provided information about gene expression trends in the germ line (for example, X-linked genes are rarely expressed in the germ line).…”

“…This study provided information about gene expression trends in the germ line (for example, X-linked genes are rarely expressed in the germ line). Piano et al [36] defined 47 patterns of defective embryogenesis associated with RNAimediated knockdown of different genes and grouped these genes into 'phenoclusters' that might reflect related gene functions. Later, Sonnichsen et al [22] applied a similar approach to classify a far larger set of genes into phenoclusters based on a set of 23 embryonic phenotypes.…”