Genetics of dementia in a Finnish cohort

European Journal of Human Genetics : EJHG
Petra PasanenAuli Verkkoniemi-Ahola

Abstract

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias. Variants in APP, PSEN1 and PSEN2 are typically linked to early-onset AD, and several genetic risk loci are associated with late-onset AD. Inherited FTD can be caused by hexanucleotide expansions in C9orf72, or variants in GRN, MAPT or CHMP2B. Several other genes have also been linked to FTD or FTD with motor neuron disease. Here we describe a cohort of 60 Finnish families with possible inherited dementia. Our aim was to clarify the genetic background of dementia in this cohort by analysing both known dementia-associated genes (APOE, APP, C9ORF72, GRN, PSEN1 and PSEN2) and searching for rare or novel segregating variants with exome sequencing. C9orf72 repeat expansions were detected in 12 (20%) of the 60 families, including, in addition to FTD, a family with neuropathologically verified AD. Twelve families (10 with AD and 2 with FTD) with representative samples from affected and unaffected subjects and without C9orf72 expansions were selected for whole-exome sequencing. Exome sequencing did not reveal any variants that could be regarded unequivocally causative, but revealed potentially damaging variants in UNC13C and M...Continue Reading

References

Sep 30, 1999·Nature Medicine·G PriharM Haltia
Jul 26, 2005·Nature Genetics·Gaia SkibinskiJohn Collinge
Feb 8, 2006·Archives of General Psychiatry·Margaret GatzNancy L Pedersen
Nov 29, 2007·European Journal of Human Genetics : EJHG·Elin S BlomMikko Hiltunen
Dec 4, 2008·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J KrügerA M Remes
Jan 13, 2009·Nature Genetics·Minerva M CarrasquilloSteven G Younkin
Apr 8, 2009·Annals of Neurology·Lina BenajibaUNKNOWN French Clinical and Genetic Research Network on Frontotemporal Lobar Degeneration/Frontotemporal Lobar Degeneration with Mot
Oct 24, 2009·Neuropathology and Applied Neurobiology·P MartikainenI Alafuzoff
Feb 4, 2010·Neurology·T Van LangenhoveC Van Broeckhoven
Mar 9, 2010·PloS One·Rita J GuerreiroJohn Hardy
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
May 13, 2010·JAMA : the Journal of the American Medical Association·Sudha SeshadriUNKNOWN EADI1 Consortium
Jun 5, 2010·Psychiatric Genetics·Gary W BeechamMargaret A Pericak-Vance
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jul 6, 2011·Nucleic Acids Research·Boris RevaChris Sander
Sep 29, 2011·Neurobiology of Aging·Edward D HueyParastoo Momeni
Jan 6, 2012·The New England Journal of Medicine·Elisa MajounieBryan J Traynor
Oct 31, 2012·Neurobiology of Aging·Martin A KohliStephan Züchner
Jan 29, 2013·Neurobiology of Aging·Rita CacaceKristel Sleegers
Apr 17, 2013·JAMA Neurology·Matthew HarmsUNKNOWN NIA-LOAD/NCRAD Family Study Consortium
May 28, 2013·Genome Medicine·Jeremy A MillerDaniel H Geschwind
Nov 1, 2013·Nucleic Acids Research·Jeffrey R MacDonaldStephen W Scherer
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow

❮ Previous
Next ❯

Citations

Nov 10, 2018·Genes, Brain, and Behavior·Jan VeveraStanislav Kmoch
Jun 7, 2019·Aging Cell·James A TimmonsClaes Wahlestedt

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
PCR
electrophoresis
Chip
Exome Capture
genotyping
ubiquitination

Software Mentioned

CADD
MutationAssessor
ANNOVAR
BWA
Polyphen2
SIFT
GATK
PolyPhen
MutationTaster

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: Genetics

Alzheimer's disease is a neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations with this feed.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.