{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T07:48:49Z","timestamp":1770882529478,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"24","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NWO domain Applied and Engineering Sciences VENI","award":["17282"],"award-info":[{"award-number":["17282"]}]},{"name":"NIH Office of Research Infrastructure Programs","award":["P40 OD010440"],"award-info":[{"award-number":["P40 OD010440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Protein aggregation of \u03b1-synuclein (\u03b1S) is a genetic and neuropathological hallmark of Parkinson\u2019s disease (PD). Studies in the model nematode Caenorhabditis elegans suggested that variation of \u03b1S aggregation depends on the genetic background. However, which genes and genetic modifiers underlie individual differences in \u03b1S pathology remains unknown. To study the genotypic-phenotypic relationship of \u03b1S aggregation, we constructed a Recombinant Inbred Line (RIL) panel derived from a cross between genetically divergent strains C. elegans NL5901 and SCH4856, both harboring the human \u03b1S gene. As a first step to discover genetic modifiers 70 \u03b1S-RILs were measured for whole-genome gene expression and expression quantitative locus analysis (eQTL) were mapped. We detected multiple eQTL hot-spots, many of which were located on Chromosome V. To confirm a causal locus, we developed Introgression Lines (ILs) that contain SCH4856 introgressions on Chromosome V in an NL5901 background. We detected 74 genes with an interactive effect between \u03b1S and the genetic background, including the human p38 MAPK homologue pmk-1 that has previously been associated with PD. Together, we present a unique \u03b1S-RIL panel for defining effects of natural genetic variation on \u03b1S pathology, which contributes to finding genetic modifiers of PD.<\/jats:p>","DOI":"10.1093\/hmg\/ddae148","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T07:45:21Z","timestamp":1729669521000},"page":"2123-2132","source":"Crossref","is-referenced-by-count":1,"title":["eQTL mapping in transgenic alpha-synuclein carrying <i>Caenorhabditis elegans<\/i> recombinant inbred lines"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4469-6746","authenticated-orcid":false,"given":"Yuqing","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiru A","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]},{"name":"Faculty of Engineering and Science, University of Greenwich , Medway ME4 4TB,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"van Sluijs","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5032-0080","authenticated-orcid":false,"given":"Demi H J","family":"Vogels","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhi","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian I P","family":"Tegelbeckers","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Schoonderwoerd","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost A G","family":"Riksen","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-4436","authenticated-orcid":false,"given":"Jan E","family":"Kammenga","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon C","family":"Harvey","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Science, University of Greenwich , Medway ME4 4TB,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark G","family":"Sterken","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology, Wageningen University & Research , Droevendaalsesteeg 1, 6708PB, Wageningen,","place":["the 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