Huntington Disease  (OMIM citation 143100)

     Progressive, degenerative neural disorder; uncontrolled ("choreic") movements
     Late onset: first symptoms may not appear until after child-bearing years
         Biochemical indications ambiguous in early stages
         A genetic counseling ethical dilemma:
              Tiresias' Dilemma: 'It is but sorrow to be wise when wisdom profits not.'

  Trinucleotide repeat variation occurs via slipped-mismatch pairing [IG1 20.Tab3]

        Huntingtin [sic] (HTT) locus [4p16.3] has (CAG)n repeat near 5' end
                 # copies in affected individuals inversely correlated with severity & age of onset
                        9 ~ 36      unaffected,
                      36 ~ 41     incomplete penetrance
                            >41      adult onset;
                            >50      juvenile onset

        huntingtin protein [sic] therefore has extra Gln residues at N-terminus
             poly-glutamine tract forms plaques on Central Nervous System

        HD therefore described as autosomal dominant:
               Phenotypic effect is a consequence of the presence of altered huntingtin protein
               in homozygotes and heterozygotes, irrespective of standard protein

                   Allele expression as poly-Gln tract "dominate" expression of non-poly-Gln tract

    (Woody Guthrie had HD: some of his tunes; Bob Dylan: Last thoughts on Woody Guthrie)  

All text material ©2016 by Steven M. Carr