Extended kindred with recessive late-onset Alzheimer disease maps to locus 8p22-p21.2: a genome-wide linkage analysis

Alzheimer Disease and Associated Disorders
Manuel BaronAdriano Jimenez-Escrig

Abstract

Late-onset Alzheimer disease (LOAD) is a complex genetic disorder. Although genes involved in early-onset forms were discovered more than a decade ago, LOAD research has only been able to point out small effect loci, with the exception of APOE. We mapped the gene predisposing to LOAD in an extended inbred family coming from a genetically isolated region (24 sampled individuals, 12 of whom are affected), completing a genome-wide screen with an Affymetrix10 K single nucleotide polymorphism microarray. Genotyping results were evaluated under model-dependent (dominant and recessive) and model-free analysis. We obtained a maximum nonparametric linkage score of 3.24 (P=0.00006) on chromosome 8p22-p21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) under a recessive model (HLOD=3.04). When we compared the results of the model-dependent analysis, a higher score was obtained in the recessive model (3.04) than in the dominant model (1.0). This is a new locus identified in LOAD, in chromosome 8p22-p21.2 and encompassing several candidate genes, among them CLU and PPP3CC that were excluded by sequencing. The finding of a recessive model of inheritance, consistent with the assumption of inbreeding a...Continue Reading

References

Nov 5, 1997·American Journal of Human Genetics·A Kong, N J Cox
Jun 23, 1998·American Journal of Human Genetics·J R O'Connell, D E Weeks
Apr 20, 1999·Genetic Epidemiology·H VézinaD Gauvreau
Dec 4, 2001·Nature Genetics·Gonçalo R AbecasisLon R Cardon
Sep 23, 2003·Journal of Molecular Neuroscience : MN·Lindsay A FarrerClinton T Baldwin
Jan 14, 2005·Bioinformatics·Franz Rüschendorf, Peter Nürnberg
Apr 22, 2005·Brain : a Journal of Neurology·Adriano Jimenez-EscrigSagrario Barquero
Jun 3, 2005·The Journal of Clinical Investigation·Lars Bertram, Rudolph E Tanzi
Feb 16, 2006·International Journal of Geriatric Psychiatry·Abdalla BowirratGiancarlo Logroscino
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kazuo YamadaTakeo Yoshikawa
Jun 8, 2007·Neuron·Eric M ReimanDietrich A Stephan
Sep 27, 2007·Molecular Psychiatry·Y HoriuchiT Arinami
Mar 19, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Heon-Jeong Lee
May 2, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·S E PodusloS Smith
Nov 13, 2008·Archives of Neurology·Joseph H LeeUNKNOWN National Institute on Aging Late-Onset Alzheimer's Disease Family Study Group
Mar 17, 2009·Science·Giuseppe Di FedeFabrizio Tagliavini
May 28, 2009·Annals of Human Genetics·Gary W BeechamMargaret A Pericak-Vance

❮ Previous
Next ❯

Citations

Nov 19, 2013·PloS One·Jonas Mengel-FromLene Christiansen
Jul 13, 2013·Journal of Neural Transmission·Amanda Taylor, Ke-Sheng Wang
Aug 13, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Rita Guerreiro, John Hardy
Nov 13, 2012·Archives of Medical Research·María Elisa Alonso VilatelaPetra Yescas-Gómez
Mar 6, 2021·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Julie HoogmartensChristine Van Broeckhoven

❮ Previous
Next ❯

Related Concepts

Related Feeds

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: 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.

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.