Importance of Genetic Model in Huntingtons Disease

Title

Importance of Genetic Model in Huntingtons Disease

Creator

Bajaj M.; Palan D.; Gandhi M.

Description

Huntingtons disease (HD) is the first defect-mapped autosomal-dominant, progressive neurodegenerative disorder with a distinct phenotype found in 1983, which contributed to the concept of human genome project. Thus, the search for genetic defects pioneered various mapping and gene study technological prototypes that culminated in identification of distinct disorders. Huntingtons disease has many symptoms, including chorea and dystonia, incoordination, cognitive decline and dementia, and behavioral difficulties. This disease can manifest any time over the age of 30 years, with the first sign and symptom being behavioral changes, which might include lack of emotions, periods of aggression, excitement, and anger. HD duration varies, ranging from 10 to 25 years or more depending on the individual. It is caused by a single gene defect on chromosome number 4, wherein a person requires only a single copy of the defected gene to show the symptoms; that is, a person with parent with the HD gene has a 50% chance of suffering. The disease becomes prominent in a human being as a result of mutations in a gene called Huntington that is located on the p arm (short arm) of chromosome 4 (4p 16.3). This chapter discusses the genetic model of Huntingtons disease and its importance. An increase in the normal number of repeat CAG (cytosine, adenine, and guanine) segments, (i.e. > 35 CAG) is seen in the Huntington (HTT) mutation that causes the disease. The severity of the disease depends on the sized expansion (i.e. increasing CAG repeats will accelerate the age of onset of the disease). Continuing studies of genetic modifiers-genes whose natural polymorphic variation contribute to the alteration and development of the D gene-offers to open new gateways for early diagnosis by unlocking the biochemical changes that occur years before diagnosis, thereby providing validated target protein and pathways for rational therapeutic interventions. This is also added as a section in this chapter. 2025 selection and editorial matter, Sachchida Nand Rai, Sandeep Singh, Santosh Kumar Singh.

Source

Neurodegenerative Diseases: Translational Models, Mechanisms, and Therapeutics, pp. 109-119.

Date

2024-01-01

Publisher

CRC Press

Coverage

Bajaj M., School of Innovation in Biodesign, Translational Health Science and Technology Institute, Faridabad, India; Palan D., School of Innovation in Biodesign, Translational Health Science and Technology Institute, Faridabad, India; Gandhi M., School of Innovation in Biodesign, Translational Health Science and Technology Institute, Faridabad, India, Department of Chemistry, CHRIST (Deemed to be University), Bengaluru, India

Rights

Restricted Access

Relation

ISBN: 978-104016012-1; 978-103261324-6

Format

Online

Language

English

Type

Book chapter

Identifier

https://doi.org/10.1201/9781032620442-9

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85210653482&doi=10.1201%2f9781032620442-9&partnerID=40&md5=bf318504ed61ee45c2185f3922bcde8a