Chapter 14 Huntingtons Disease Imprinting and Genetic Anticipation

Chapter 14 Huntington’s Disease Imprinting and Genetic Anticipation

History of Huntington’s Disease l 1630, 3 men escaped to America l l l Wilke, Nichols, and Jeffers Families had been persecuted for witchcraft One man settled in the Hampton’s(NY) l Offspring were notorious for a strange and frightening disease

Initial Symptoms Irritability l Clumsiness l Depression l Forgetfulness l Mood and personality changes l Uncontrollable movements l Hard to swallow l

George Huntington l l Huntington’s had 3 generations of doctors Youngest was George Huntington Jr Made rounds via horseback with father 1872, George Huntington Jr wrote a paper “ On Chorea”

Chorea l l Chorea means to dance “dancing disorder” l l l Uncontrollable jerking and moving People were thought to be possessed by devils One of the “witches” executed in Salem, MA had Huntington’s disease

Ex. Wilke’s Children l l l One of the 3 original British men who fled to America Professional carpenter w/ 7 children Son marries Elizabeth Warne who returns to England, tried as a witch l l child with strange convulsions) Elizabeth's child is tried as the "Groton Witch" http: //www. medinfo. ufl. edu/other/histmed/okun/slide 27. html

Huntington’s Disease l Caused by a dominant gene l Diagnosed 35 -60 years old l Average of onset=40 years l Progressive l Continually l No remission l No l getting worse breaks or getting better ALWAYS fatal l Usually only 20 more years after diagnosis

Interesting Weirdness l Maternal Allele l If you inherit huntingtons allele from mom l l Paternal Allele: l If you inherit huntingtons allele from dad l l Normal onset(35 -50 years) You show symptoms at earlier age Thanks a lot dad!!! MOM H h DAD h Hh hh normal onset MOM h h DAD H Hh Hh h hh hh show symptoms earlier

Genomic Imprinting In some diseases, it matters which parent gave you the gene!!! l A mysterious phenomena l l We still don’t fully understand it

Genomic Imprinting At least 100 genes are imprinted l You must re-imprint genes from you parents before you pass them on to your children l

Another weird thing about Huntington’s Disease Example of anticipation l Symptoms start showing up earlier in families l Genetic anticipation l

Genetic Anticipation in Huntington’s Disease DNA has regions of repeating sequences l Trinucleotide repeats l l Makes gene more and more unstable Ex. CAGCAGCAGCAGCAG or TCGTCGTCGTCGTCGTCT

CAG repeats Huntington’s is caused by too much repeats l End of chromosome 4 l l CAG repeats Normal gene has 11 -34 copies of CAG l Mutation increases it to more than 37 l In HD, Passing on chromosome 4 Increases # of repeats l l Symptoms start showing earlier