دورية أكاديمية
Unraveling the complex role of MAPT-containing H1 and H2 haplotypes in neurodegenerative diseases
| العنوان: | Unraveling the complex role of MAPT-containing H1 and H2 haplotypes in neurodegenerative diseases |
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| المؤلفون: | Chiara Pedicone, Sarah A. Weitzman, Alan E. Renton, Alison M. Goate |
| المصدر: | Molecular Neurodegeneration, Vol 19, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Neurology. Diseases of the nervous system LCC:Geriatrics |
| مصطلحات موضوعية: | 17q21.31, Haplotypes, Inversion, Neurodegeneration, SNV, CNV, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6 |
| الوصف: | Abstract A ~ 1 Mb inversion polymorphism exists within the 17q21.31 locus of the human genome as direct (H1) and inverted (H2) haplotype clades. This inversion region demonstrates high linkage disequilibrium, but the frequency of each haplotype differs across ancestries. While the H1 haplotype exists in all populations and shows a normal pattern of genetic variability and recombination, the H2 haplotype is enriched in European ancestry populations, is less frequent in African ancestry populations, and nearly absent in East Asian ancestry populations. H1 is a known risk factor for several neurodegenerative diseases, and has been associated with many other traits, suggesting its importance in cellular phenotypes of the brain and entire body. Conversely, H2 is protective for these diseases, but is associated with predisposition to recurrent microdeletion syndromes and neurodevelopmental disorders such as autism. Many single nucleotide variants and copy number variants define H1/H2 haplotypes and sub-haplotypes, but identifying the causal variant(s) for specific diseases and phenotypes is complex due to the extended linkage equilibrium. In this review, we assess the current knowledge of this inversion region regarding genomic structure, gene expression, cellular phenotypes, and disease association. We discuss recent discoveries and challenges, evaluate gaps in knowledge, and highlight the importance of understanding the effect of the 17q21.31 haplotypes to promote advances in precision medicine and drug discovery for several diseases. Graphical Abstract |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1750-1326 |
| العلاقة: | https://doaj.org/toc/1750-1326Test |
| DOI: | 10.1186/s13024-024-00731-x |
| الوصول الحر: | https://doaj.org/article/306129aff2bd49389e957859537beb0eTest |
| رقم الانضمام: | edsdoj.306129aff2bd49389e957859537beb0e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17501326 |
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| DOI: | 10.1186/s13024-024-00731-x |