# A combined approach exploring gene function based on Worm-Human Orthology

**Authors:** Ivica Tamas, Emily Hodges, Patrick Dessi, Robert Johnsen, Ana Vaz Gomes

PMC · DOI: 10.1186/1471-2164-6-65 · 2005-05-06

## TL;DR

This study uses C. elegans and human cells to explore the function of genes with unknown roles, revealing new expression patterns and RNAi effects.

## Contribution

The novel approach combines worm RNAi and human cell over-expression to infer gene functions across species.

## Key findings

- Four C. elegans genes showed previously unknown expression patterns.
- Four RNAi phenotypes were observed in down-regulated worm genes.
- Subcellular over-expression profiles of human orthologs were analyzed for seven genes.

## Abstract

Many aspects of the nematode Caenorhabditis elegans biology are conserved between invertebrates and vertebrates establishing this particular organism as an excellent genetic model. Because of its small size, large populations and self-fertilization of the hermaphrodite, functional predictions carried out by genetic modifications as well as RNAi screens, can be rapidly tested.

In order to explore the function of a set of C. elegans genes of unknown function, as well as their potential functional roles in the human genome, we performed a phylogenetic analysis to select the most probable worm orthologs. A total of 13 C. elegans genes were subjected to down- regulation via RNAi and characterization of expression profiles using GFP strains. Previously unknown distinct expression patterns were observed for four of the analyzed genes, as well as four visible RNAi phenotypes. In addition, subcellular protein over-expression profiles of the human orthologs for seven out of the thirteen genes using human cells were also analyzed.

By combining a whole-organism approach using C. elegans with complementary experimental work done on human cell lines, this analysis extends currently available information on the selected set of genes.

## Linked entities

- **Species:** Caenorhabditis elegans (taxon 6239), Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** TRAT1 (T cell receptor associated transmembrane adaptor 1) [NCBI Gene 50852] {aka HSPC062, TCRIM, TRIM, pp29/30}, LMNA (lamin A/C) [NCBI Gene 4000] {aka CDCD1, CDDC, CMD1A, CMT2B1, EMD2, FPL}, CHSY1 (chondroitin sulfate synthase 1) [NCBI Gene 22856] {aka CHSY, CSS1, ChSy-1, TPBS}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, sqv-5 (Chondroitin sulfate synthase sqv-5;Hexosyltransferase) [NCBI Gene 172851], CTDSP1 (CTD small phosphatase 1) [NCBI Gene 58190] {aka NIF3, NLI-IF, NLIIF, SCP1}, Enpp1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) [NCBI Gene 18605] {aka 4833416E15Rik, CD203c, E-NPP 1, E-NPP1, Ly-41, M6S1}, CTDSPL (CTD small phosphatase like) [NCBI Gene 10217] {aka C3orf8, HYA22, PSR1, RBSP3, SCP3}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, FLVCR2 (FLVCR choline and putative heme transporter 2) [NCBI Gene 55640] {aka C14orf58, CCT, EPV, FLVCRL14q, MFSD7C, PVHH}, ANXA2 (annexin A2) [NCBI Gene 302] {aka ANX2, ANX2L4, CAL1H, HEL-S-270, LIP2, LPC2}, IMP4 (IMP U3 small nucleolar ribonucleoprotein 4) [NCBI Gene 92856] {aka BXDC4}, QNG1 (Q-nucleotide N-glycosylase 1) [NCBI Gene 84267] {aka C9orf64}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, BTBD1 (BTB domain containing 1) [NCBI Gene 53339] {aka C15orf1, NS5ATP8}, TRIP10 (thyroid hormone receptor interactor 10) [NCBI Gene 9322] {aka CIP4, HSTP, STOT, STP, TRIP-10}, EMB (embigin) [NCBI Gene 133418] {aka GP70}, FBL (fibrillarin rRNA 2'-O-methyltransferase) [NCBI Gene 2091] {aka FIB, FLRN, Nop1, RNU3IP1}, MARCHF3 (membrane associated ring-CH-type finger 3) [NCBI Gene 115123] {aka MARCH-III, MARCH3, RNF173}, Anxa2 (annexin A2) [NCBI Gene 12306] {aka Cal1h, PAP-IV, p36}, BTBD2 (BTB domain containing 2) [NCBI Gene 55643], rrf-3 (RNA-directed RNA polymerase) [NCBI Gene 174315]
- **Diseases:** tumor (MESH:D009369), embryonic lethality (MESH:D020964), CMV (MESH:D003586)
- **Species:** Homo sapiens (human, species) [taxon 9606], Escherichia coli HT115 (strain) [taxon 634469], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Escherichia coli (E. coli, species) [taxon 562], Gallus sp. (species) [taxon 9036], C. elegans [taxon 328850], Drosophila melanogaster (fruit fly, species) [taxon 7227], Caenorhabditis elegans (species) [taxon 6239], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** T24D
- **Cell lines:** F41D9.1 — Mus musculus (Mouse), Mouse teratocarcinoma, Cancer cell line (CVCL_8300), JM109 — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0065), ZK795.3 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_A5XI), C05C8.6 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_XJ14), C17E4.3 — Mus musculus (Mouse), Hybridoma (CVCL_B5A6), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), NL2099 — Homo sapiens (Human), Nevoid basal cell carcinoma syndrome, Transformed cell line (CVCL_2Z73), C09D4.1 — Mus musculus (Mouse), Hybridoma (CVCL_C5MM), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), T24D1.1a — Homo sapiens (Human), Type 1 diabetes mellitus, Induced pluripotent stem cell (CVCL_A9M3), rrf-3 — Mus musculus (Mouse), Hybridoma (CVCL_C6V6)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC1112593/full.md

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Source: https://tomesphere.com/paper/PMC1112593