Ultra-rare complement factor 8 coding variants in families with age-related macular degeneration.

Genetics Molecular Genetics Molecular Structure Molecular biology Molecular interaction

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
21 Apr 2023
Historique:
received: 05 12 2022
revised: 20 02 2023
accepted: 11 03 2023
medline: 8 5 2023
pubmed: 8 5 2023
entrez: 8 5 2023
Statut: epublish

Résumé

Genome-wide association studies have uncovered 52 independent common and rare variants across 34 genetic loci, which influence susceptibility to age related macular degeneration (AMD). Of the 5 AMD-associated complement genes, complement factor H (CFH) and CFI exhibit a significant rare variant burden implicating a major contribution of the complement pathway to disease pathology. However, the efforts for developing AMD therapy have been challenging as of yet. Here, we report the identification of ultra-rare variants in complement factors 8A and 8B, two components of the terminal complement membrane attack complex (MAC), by whole exome sequencing of a cohort of AMD families. The identified C8 variants impact local interactions among proteins of C8 triplex

Identifiants

pubmed: 37153444
doi: 10.1016/j.isci.2023.106417
pii: S2589-0042(23)00494-7
pmc: PMC10156737
doi:

Types de publication

Journal Article

Langues

eng

Pagination

106417

Déclaration de conflit d'intérêts

The authors declare no competing interests.

Références

Immunol Lett. 2012 Sep;147(1-2):29-33
pubmed: 22698681
FEBS J. 2023 Jan;290(1):28-36
pubmed: 34767301
Arch Ophthalmol. 2001 Oct;119(10):1417-36
pubmed: 11594942
Int J Mol Sci. 2021 Jun 25;22(13):
pubmed: 34202223
JAMA Ophthalmol. 2013 Jul;131(7):843-50
pubmed: 23645227
Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303
pubmed: 29788355
J Cell Sci. 2013 Jul 1;126(Pt 13):2903-13
pubmed: 23613465
PLoS One. 2011 Apr 28;6(4):e19078
pubmed: 21552568
Annu Rev Genomics Hum Genet. 2009;10:19-43
pubmed: 19405847
Proteins. 2009;77 Suppl 9:114-22
pubmed: 19768677
Nat Rev Dis Primers. 2021 May 6;7(1):31
pubmed: 33958600
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Annu Rev Genomics Hum Genet. 2014;15:151-71
pubmed: 24773320
Nat Genet. 2016 Feb;48(2):134-43
pubmed: 26691988
Hum Mol Genet. 2020 Jul 29;29(12):2022-2034
pubmed: 32246154
JCI Insight. 2020 Apr 9;5(7):
pubmed: 32191644
Sci Rep. 2017 Sep 5;7(1):10480
pubmed: 28874689
Arch Ophthalmol. 2005 Nov;123(11):1570-4
pubmed: 16286620
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W382-8
pubmed: 15980494
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Cell Mol Life Sci. 2021 May;78(10):4487-4505
pubmed: 33751148
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Bioinformatics. 2014 Oct 15;30(20):2981-2
pubmed: 24996895
Circ Res. 2019 Jun 7;124(12):1747-1759
pubmed: 31170059
Am J Hum Genet. 2003 Sep;73(3):540-50
pubmed: 12900797
Gigascience. 2021 Feb 16;10(2):
pubmed: 33590861
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Mol Ther. 2018 Jun 6;26(6):1568-1580
pubmed: 29678656
Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):
pubmed: 34620711
STAR Protoc. 2021 Jul 06;2(3):100644
pubmed: 34278331
Hum Mol Genet. 2022 Feb 3;31(3):455-470
pubmed: 34508573
Invest Ophthalmol Vis Sci. 2013 Jan 07;54(1):110-20
pubmed: 23221073
Lancet Glob Health. 2014 Feb;2(2):e106-16
pubmed: 25104651
Ophthalmic Physiol Opt. 2020 Mar;40(2):140-170
pubmed: 32100327
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Am J Pathol. 2020 Jun;190(6):1138-1150
pubmed: 32194049
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Front Immunol. 2021 Sep 28;12:720655
pubmed: 34650553
J Immunol. 1998 Oct 1;161(7):3762-6
pubmed: 9759902
Nat Commun. 2016 Feb 04;7:10587
pubmed: 26841837
Brain. 2021 Mar 3;144(2):528-552
pubmed: 33382892
Hum Mol Genet. 2021 Jun 17;30(13):1188-1199
pubmed: 33783477

Auteurs

Lina Zelinger (L)

Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Tammy M Martin (TM)

Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, OR, USA.
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.

Jayshree Advani (J)

Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Laura Campello (L)

Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Milton A English (MA)

Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Alan Kwong (A)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
23andMe, Inc, Sunnyvale, CA, USA.

Claire Weber (C)

Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Jennifer Maykoski (J)

Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, OR, USA.

Yuri V Sergeev (YV)

Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Robert Fariss (R)

Biological Imaging Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Emily Y Chew (EY)

Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Michael L Klein (ML)

Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, OR, USA.

Anand Swaroop (A)

Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Classifications MeSH