HTT evolution and brain development

Huntingtin (htt) is the 800 million-year-old 3,144 amino acid protein product of the Huntington\u2019s disease (HD) gene, which carries a tri-nucleotide CAG repeat then translated into polyglutamine (polyQ) at an evolutionarily conserved NH2-terminal position in exon 1. The CAG triplet is polymorphic in the normal population, ranging from 9 to 32 repetitions. In humans, an expansion of the repeats to more than 35 causes HD, a fatal, genetically dominant neurodegenerative disorder (MacDonald et al., Cell 72:971\u2013983, 1993)