C. elegans has phenotypes that can be directly related to human genes, with homologs identified for up to 80% of human genes
Some of the most economically and socially impactful diseases in our time are known to have genetic risk factors. Through basic and clinical research, top genes that are mutated in each disease have been identified. C. elegans has homologs to many of these genes because the biochemical signaling pathways that underlie them are evolutionarily old.
Here we provide a table of the top genes associated with some high-impact diseases and the corresponding C. elegans gene. Interestingly, mutations to the homologous genes in C. elegans create quantifiable phenotypes that allow researchers to delve deeper into biological mechanism and screen compounds that may affect the phenotypic expression of a disease-associated mutation.
Linking human disease genes and C. elegans genes and their corresponding phenotypes. Learn more.
Alzheimer’s
Human Phenotype
Memory loss
Plaques: a-beta protein accumulation
Neurofibrillary tangles, tau tangles
Worm Phenotype
Weakened neuromuscluar function
| Human Gene | Worm Gene Homolog |
|---|---|
| PSEN1 | sel-12 |
| APP | apl-1 |
| APOE | [Not Identified] |
| PSEN2 | sel-12 |
| SORL1 | egg-1 |
| MAPT | ptl-1 |
| BDNF | [Not Identified] |
| IL1B | C44B12.6 |
| BACE1 | asp-15 |
| ACE | acn-1 |
Amyotrophic Lateral Sclerosis
Human Phenotype
Progressive motor neuron weakness
Worm Phenotype
Weakend muscular contraction
| Human Gene | Worm Gene Homolog |
|---|---|
| TARDBP | tdp-1 |
| UNC13A | unc-13 |
| SOD1 | sod-1 |
| SQSTM1 | sqst-4 |
| CHMP2B | C01A2.4 |
| C9ORF72 | alfa-1 |
| PON1 | poml-2 |
| FUS | fust-1 |
| ANG | [Not Identified] |
| VCP | cdc-48.1, cdc-48.2 |
| ATXN2 | atx-2 |
Spinal Muscular Atrophy
Human Phenotype
progressive motor neuron degeneration, muscle weakness
Worm Phenotype
Weakened muscular contraction
| Human Gene | Worm Gene Homolog |
|---|---|
| SMN1 | smn-1 |
| SMN2 | smn-1 |
| DYNC1H1 | dhc-1 |
| TRPV4 | osm-9 |
| BICD2 | bicd-1 |
| IGHMBP2 | eri-7 |
| VRK1 | vrk-1 |
| UBA1 | uba-1 |
| ASAH1 | asah-1 |
| VAPB | vpr-1 |
Parkinsons
Human Phenotype
Muscular weakness
Dopaminergic signaling loss
| Human Gene | Worm Gene Homolog |
|---|---|
| LRRK2 | lrk-1, |
| SNCA | [Not Identified] |
| PARK2 | pdr-1 |
| PINK1 | pink-1 |
| MAPT | ptl-1 |
| GBA | gba-3, gba-4, gba-1, gba-2 |
| PARK7 | djr-1.1, djr-1.2 |
| DRD1 | dop-1 |
| IGF1R | daf-2 |
| MAOB | amx-2, amx-1 |
Premature Aging
| Human Gene | Worm Gene Homolog |
|---|---|
| WRN | wrn-1, K02F3.12, him-6 |
| KL | klo-1, klo-2 |
| ERCC6 | csb-1, btf-1, F53H4.6 |
| APP | apl-1 |
| LMNA | lmn-1, ifa-1, ifb-1 |
| BLM | him-6 |
| ELK1 | lin-1 |
| ZMPSTE24 | fce-1 |
| RECQL4 | wrn-1 |
| TP53 | [Not Identified] |
Schizophrenia
| Human Gene | Worm Gene Homolog |
|---|---|
| MAGI2 | magi-1 |
| DISC1 | myo-5 |
| DTNBP1 | dsbn-1 |
| COMT | comt-3, comt-2, comt-4, comt-1 |
| HTR2A | ser-1 |
| NRG1 | igeg-1 |
| GJA8 | [Not Identified] |
| DISC2 | [Not Identified] |
| ATP2A2 | sca-1, pmr-1 |
| GJA5 | [Not Identified] |
Linking human disease genes and C. elegans genes and their corresponding phenotypes.
Although the phenotypes of the human diseases and the mutant defects in C. elegans seem about as unrelated as possible, the cellular and molecular details of many of these defects are highly related. Using C. elegans as a model organism, much can be learned at the cellular and molecular level about a specific biological process, by understanding the mode of action of the orthologous genes involved.