HD is neurodegenerative/poly glutamine/autosomal dominant disease that involve gene HTT located on autosomal

chromosome number 4 the expanded CAG repeats effect DNA replication itself when copying HTT gene DNA
polymerase basically lose track of STR(short tandem repeat) in microsatellite of which CAG it's on and
accidentally stutters and add extra CAG^s.

Huntingtin protein; From immunohistochemistry, electron microscopy, and subcellular fractionation studies of the
molecule, it has been found that huntingtin is primarily associated with vesicles and microtubules.[12][13] These
appear to indicate a functional role in cytoskeletal anchoring or transport of mitochondria. The Htt protein is
involved in vesicle trafficking as it interacts with HIP1, a clathrin-binding protein, to mediate endocytosis, the
trafficking of materials into a cell.[14][15] Huntingtin has also been shown to have a role in the establishment in
epithelial polarity

*How its differently inherited by male and female?*

Since at time of egg and sperm several dozens of cell division and each with a round of DNA replication so increase
in repeat expansion increases instability and early onset of the HD with each generation. People with Huntington
disease have more than equal to 36 glutamine in a row however ones with 27-35 CAG repeats are called pre-mutated
allele since it does not cause disease but develops mutation of 36 or more CAGs.Because of this 100% penetrance
test for HD is counting no. Of CAGs repeats to determine at risk individual. Onset of disease is dependent on
number of repeats & common in middle age.

Symptoms; neuronal cell death leads to brain cell lost brain tissue volume lost in the area that have role in
movement so involuntary muscular movement like chorea and athetosis (wriggling of hand ) plus expansion of
lateral ventricle leading to psychological disorders like dementia and depression and cognitive problem inclusive of
mental deterioration and abnormal eye movement plus poor coordination etc.

Not truly Mendelian (where there is 50-50 chance of passing the disease(1 in 2)+ most sufferers are heterozygotes )