Genetic Testing for Huntington`s Disease

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Genetic Testing for Huntington 's disease

Huntington 's disease (HD ) is a late onset , progressive type of neurodegenerative

disease which is characterized by progressively worsening physical and mental abnormalities ,1 and finally death (Walker , 218 . Though symptoms of HD can appear at any age from 1 to 80 years , they most commonly appear in an individual between 30 to 50 years of age and progress over a span of 10 to 25 years (Walker , 218 . HD affects the

individual 's ability to think , speak and walk . HD is a hereditary dis which is inherited in an autosomal dominant pattern1 . This means that every child born to a person , who has HD , regardless of gender , has a 50 chance of inheriting the gene that causes HD (as shown in figure 1 . Since the defect is on autosomes , men and women are equally affected , so either parent may pass on the HD gene to any offspring (Meiser Dunn , 575 Every person who inherits the HD gene will eventually develop the disease while non carriers will definitely not develop the disease . Thus if one does not inherit the gene , one cannot pass it on

1 To understand the exact clinical course followed by HD see the article Huntington 's disease ' by Walker , Francis O . in the Lancet . 369 9557 (2007 ) especially page 218-219

2 Autosomal dominant inheritance implies that person needs to have only one mutant gene to express this disease phenotypically and he can inherit it from either of his parents (Walker , 218 . Also see figure .1

Figure 1 . Autosomal Dominant Pedigree Chart

Source : Walker Jeremy . Autosomal Dominant Pedigree Chart . 2006 . Accessed 7 April 2007 Genetic Defect Involved in Huntington 's disease

The gene which undergoes mutation resulting in HD lies on the short arm of chromosome

4 (Walker 220 . The normal gene is actually a segment of DNA which contains a strip of trinucleotide sequences usually of the type cytosine-adenine-guanine (CAG ) at one end . Mutation of this gene results in expansion of these unstable trinucleotide CAG repeat sequences (Walker 220 .Everyone has two copies of the normal gene . The people with HD have mutation of one of these genes . The causative mutation in HD is in the first exon of the IT15 gene on chromosome 42 .The mutation results in abnormal production of glutamine (amino acid represented by CAG which can aggregate to form polyglutamine chains (Walker 222 Development of HD depends on number of CAG repeats contained within the copies of the HD genes . When the number of these CAG repeats is 41 or more , the disease is fully penetrant (i .e . expresses itself completely . Incomplete penetrance is observed in people who have between 36-40 CAG repeats . If number of these CAG repeats is 35 or less the disease does not manifest itself (Walker , 220 . The number of CAG repeats may change as the gene passes from parent to child . Thus the child may show slightly fewer or slightly...