Chapter 41 Genetics of Neurodegenerative Diseases Copyright 2012

Chapter 41 Genetics of Neurodegenerative Diseases Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 1

TABLE 41 -1 A: Genes Causing Mendelian Forms of Alzheimer’s Disease Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 2

TABLE 41 -1 B: Susceptibility Genes for Non-Mendelian Forms of Alzheimer’s Disease Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 3

TABLE 41 -2 A: Genes Causing Mendelian Forms of Parkinson’s Disease Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 4

TABLE 41 -2 B: Susceptibility Genes for Non-Mendelian Forms of Parkinson’s Disease Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 5

TABLE 41 -3 A: Genes Causing Mendelian Forms of Frontotemporal Dementia Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 6

TABLE 41 -3 B: Susceptibility Genes for Non-Mendelian Forms of Frontotemporal Dementia Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 7

TABLE 41 -4 A: Genes Causing Mendelian Forms of Amyotrophic Lateral Sclerosis Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 8

TABLE 41 -4 B: Susceptibility Genes for Non-Mendelian Forms of Amyotrophic Lateral Sclerosis Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 9

FIGURE 41 -1: This schema outlines popular strategies to identify mutations and polymorphisms causing or predisposing to disease. Depending on the observed or suspected mode of inheritance, the search for disease-related sequence variants typically involves mutation screenings (Mendelian forms) or association analyses (non-Mendelian or sporadic forms). “Focused” in this context usually entails the study of certain gene(s) (usually considered “candidate genes” based on evidence from functional experiments or genetic linkage data), while “systematic” refers to large-scale approaches unbiased with respect to the nature of the underlying genes. The latter can be achieved by applying sequencing or genotyping technologies such as high-throughput next-generation sequencing (NGS, analyzing the entire exome or genome), or genome-wide association studies (GWAS). Initial findings are followed up depending on the original design, and are subsequently (or simultaneously) subjected to functional characterization. Broken lines indicate “short-cuts” allowing definition of novel disease genes based on the genetic evidence alone, which is the case for most of the currently known susceptibility genes in the neurodegenerative disease field. Note examples of genes/mutations with reduced penetrance (left-hand red box) that are considered bona-fide disease genes (e. g. , certain mutations in PSEN 1 in Alzheimer’s disease). Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 10