
Contents
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Introduction Introduction
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Tools for Mapping the Genetic Landscape of ALS Tools for Mapping the Genetic Landscape of ALS
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Rare, Large Effect Variation: Family Studies and Next-Generation Sequencing Rare, Large Effect Variation: Family Studies and Next-Generation Sequencing
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Common Variation with Small Effects: Population-Based Genome-wide Association Studies Common Variation with Small Effects: Population-Based Genome-wide Association Studies
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Low Frequency and Rare Variation with Small or Modest Effects Low Frequency and Rare Variation with Small or Modest Effects
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The Landscape of ALS Genetics The Landscape of ALS Genetics
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High Penetrance Genes High Penetrance Genes
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Potential Oligogenic Influences Potential Oligogenic Influences
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Risk Factors for ALS Risk Factors for ALS
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Genes Implicated by Candidate Gene Approaches Genes Implicated by Candidate Gene Approaches
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ATXN2 Intermediate Repeats ATXN2 Intermediate Repeats
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TREM2 R47H TREM2 R47H
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PFN1 E117G PFN1 E117G
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EPH4A EPH4A
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Paroxonase Paroxonase
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Genes Implicated by Genome-Wide Association Studies Genes Implicated by Genome-Wide Association Studies
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Insights from Genetics on Disease Pathogenesis Insights from Genetics on Disease Pathogenesis
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Known Genes Suggest Multiple Routes to Motor Neuronal Loss Known Genes Suggest Multiple Routes to Motor Neuronal Loss
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ALS Is Likely To Be a Multistep Disease ALS Is Likely To Be a Multistep Disease
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Insights from Genetics on Development of Therapeutics Insights from Genetics on Development of Therapeutics
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Insights from Genetics for Diagnosis and Clinical Care Insights from Genetics for Diagnosis and Clinical Care
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References References
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27 Amyotrophic Lateral Sclerosis: Insights from Genetics
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Published:August 2016
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Abstract
Recent advances in sequencing technologies have dramatically expanded the number of genes associated with amyotrophic lateral sclerosis, including rare but highly penetrant causative mutations as well as common risk alleles. This chapter discusses these gene discoveries and how they have implicated a diverse array of biological pathways essential for motor neuron health and have begun to inform our understanding of ALS pathogenesis as a heterogeneous and multistep process. Insights from these discoveries are leading to a new generation of targeted therapies directed at specific genes and are poised to inform how patients with amyotrophic lateral sclerosis are evaluated and treated in the clinic.
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