Chapter 22, Problem 26P

ALS (amyotrophic lateral sclerosis) is a rare, fatal neurodegenerative disease that is genetically complex. During the last several years, using GWAS analyses and other methods, 11 different genes have been identified that are thought to be connected with ALS. The most recently discovered of these genes, TBK1, was identified through analysis of the whole exome sequences of several thousand Cases and Controls. Recall from Chapter 11 that the exome is the approximately 1% of the human genome that corresponds to exons. Each person’s exome sequence was evaluated on a gene-by-gene basis as to whether or not a SNP variant likely to alter gene function was present. The TBK1 gene was not identified in previous GWAS analyses that genotyped similar numbers of individuals for common SNPs. Cite possible explanations for the different outcomes of these two experiments.