van Doormaal, Perry T. C., Ticozzi, Nicola ORCID: 0000-0001-5963-7426, Weishaupt, Jochen H., Kenna, Kevin, Diekstra, Frank P., Verde, Federico ORCID: 0000-0002-3977-6995, Andersen, Peter M., Dekker, Annelot M., Tiloca, Cinzia, Marroquin, Nicolai, Overste, Daniel J., Pensato, Viviana ORCID: 0000-0001-9798-2669, Nuernberg, Peter, Pulit, Sara L., Schellevis, Raymond D., Calini, Daniela, Altmueller, Janine, Francioli, Laurent C., Muller, Bernard, Castellotti, Barbara, Motameny, Susanne, Ratti, Antonia, Wolf, Joachim, Gellera, Cinzia, Ludolph, Albert C., van den Berg, Leonard H., Kubisch, Christian ORCID: 0000-0003-4220-0978, Landers, John E., Veldink, Jan H., Silani, Vincenzo and Volk, Alexander E. (2017). The role of de novo mutations in the development of amyotrophic lateral sclerosis. Hum. Mutat., 38 (11). S. 1534 - 1542. HOBOKEN: WILEY. ISSN 1098-1004

Full text not available from this repository.

Abstract

The genetic basis combined with the sporadic occurrence of amyotrophic lateral sclerosis (ALS) suggests a role of de novo mutations in disease pathogenesis. Previous studies provided some evidence for this hypothesis; however, results were conflicting: no genes with recurrent occurring de novo mutations were identified and different pathways were postulated. In this study, we analyzed whole-exome data from 82 new patient-parents trios and combined it with the datasets of all previously published ALS trios (173 trios in total). The per patient de novo rate was not higher than expected based on the general population (P = 0.40). We showed that these mutations are not part of the previously postulated pathways, and gene-gene interaction analysis found no enrichment of interacting genes in this group (P = 0.57). Also, we were able to show that the de novo mutations in ALS patients are located in genes already prone for de novo mutations (P < 1 x 10(-15)). Although the individual effect of rare de novo mutations in specific genes could not be assessed, our results indicate that, in contrast to previous hypothesis, de novo mutations in general do not impose a major burden on ALS risk.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
van Doormaal, Perry T. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ticozzi, NicolaUNSPECIFIEDorcid.org/0000-0001-5963-7426UNSPECIFIED
Weishaupt, Jochen H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kenna, KevinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diekstra, Frank P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verde, FedericoUNSPECIFIEDorcid.org/0000-0002-3977-6995UNSPECIFIED
Andersen, Peter M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dekker, Annelot M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tiloca, CinziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marroquin, NicolaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Overste, Daniel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pensato, VivianaUNSPECIFIEDorcid.org/0000-0001-9798-2669UNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pulit, Sara L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schellevis, Raymond D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Calini, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Francioli, Laurent C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castellotti, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Motameny, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ratti, AntoniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gellera, CinziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludolph, Albert C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Berg, Leonard H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubisch, ChristianUNSPECIFIEDorcid.org/0000-0003-4220-0978UNSPECIFIED
Landers, John E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veldink, Jan H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silani, VincenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volk, Alexander E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-213423
DOI: 10.1002/humu.23295
Journal or Publication Title: Hum. Mutat.
Volume: 38
Number: 11
Page Range: S. 1534 - 1542
Date: 2017
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1098-1004
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FAMILIAL ALS; SPORADIC ALS; VARIANTS; DISEASE; POPULATION; PATTERNS; TRIOS; RISK; AGEMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21342

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item