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2. Supplemental Material - Palliative Care across Settings: Perspectives from Inpatient, Primary Care, and Home Health Care Providers and Staff

Author

Tietbohl, Caroline K., Dafoe, Ashley, Jordan, Sarah R., Huebschmann, Amy G., Lum, Hillary D., Bowles, Kathryn H., and Jones, Christine D.

Subjects
111099 Nursing not elsewhere classified, 111702 Aged Health Care, FOS: Health sciences
Abstract

Supplemental Material for Palliative Care across Settings: Perspectives from Inpatient, Primary Care, and Home Health Care Providers and Staff by Caroline K. Tietbohl, Ashley Dafoe, Sarah R. Jordan, Amy G. Huebschmann, Hillary D. Lum, Kathryn H. Bowles, and Christine D. Jones in American Journal of Hospice and Palliative Medicine®

Published
2023
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3. Additional file 4 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 4. Supplementary fig 4

Published
2022
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4. Additional file 9 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 9. Supplementary table 2

Published
2022
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5. Additional file 5 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 5. Supplementary fig 5

Published
2022
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6. Additional file 2 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 2. Supplementary fig 2

Published
2022
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7. Additional file 10 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 10. Supplementary table 3

Published
2022
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8. Additional file 3 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 3. Supplementary fig 3

Published
2022
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9. Additional file 7 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 7. Supplementary fig 7

Published
2022
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10. Additional file 1 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 1. Supplementary fig 1

Published
2022
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11. Additional file 6 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 6. Supplementary fig 6

Published
2022
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12. Additional file 14 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 14. Supplementary table 7

Published
2022
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13. Additional file 11 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 11. Supplementary table 4

Published
2022
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14. Additional file 15 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 15. Supplementary table 8

Published
2022
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15. Additional file 13 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 13. Supplementary table 6

Published
2022
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16. 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson's disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R, Pugh, Derian A, Cherry, Jonathan D, Karch, Celeste M, Frucht, Steven J, Kopell, Brian H, Peter, Inga, Park, Y. J., Consortium, International Parkinson’s Disease Genomics, Charney, Alexander, Raj, Towfique, Crary, John F, Liu, Yiyuan, Goate, A. M., Patel, Tulsi, Renton, Alan E, Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, and Bertelsen, Sarah

Subjects
DNA Copy Number Variations, genetics [DNA Copy Number Variations], Copy number variation, LRRC37A, 17q21.31, Parkinson Disease, tau Proteins, Polymorphism, Single Nucleotide, pathology [Parkinson Disease], genetics [tau Proteins], Haplotypes, genetics [Parkinson Disease], ddc:570, Astrocytes, genetics [alpha-Synuclein], Parkinson’s disease, alpha-Synuclein, Humans, Genetic Predisposition to Disease, pathology [Astrocytes]
Abstract

Parkinson's disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified.To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain tissue.We identified three novel H1 sub-haplotype blocks across the 17q21.31 locus associated with PD risk. Protective sub-haplotypes were associated with increased LRRC37A/2 copy number and expression in human brain tissue. We found that LRRC37A/2 is a membrane-associated protein that plays a role in cellular migration, chemotaxis and astroglial inflammation. In human substantia nigra, LRRC37A/2 was primarily expressed in astrocytes, interacted directly with soluble α-synuclein, and co-localized with Lewy bodies in PD brain tissue.These data indicate that a novel candidate gene, LRRC37A/2, contributes to the association between the 17q21.31 locus and PD via its interaction with α-synuclein and its effects on astrocytic function and inflammatory response. These data are the first to associate the genetic association at the 17q21.31 locus with PD pathology, and highlight the importance of variation at the 17q21.31 locus in the regulation of multiple genes other than MAPT and KANSL1, as well as its relevance to non-neuronal cell types.

Published
2021
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17. A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies

Author

Karch, Celeste M, Kao, Aimee W, Karydas, Anna, Onanuga, Khadijah, Martinez, Rita, Argouarch, Andrea, Wang, Chao, Huang, Cindy, Sohn, Peter Dongmin, Bowles, Kathryn R, Spina, Salvatore, Silva, M Catarina, Marsh, Jacob A, Hsu, Simon, Pugh, Derian A, Ghoshal, Nupur, Norton, Joanne, Huang, Yadong, Lee, Suzee E, Seeley, William W, Theofilas, Panagiotis, Grinberg, Lea T, Moreno, Fermin, McIlroy, Kathryn, Boeve, Bradley F, Cairns, Nigel J, Crary, John F, Haggarty, Stephen J, Ichida, Justin K, Kosik, Kenneth S, Miller, Bruce L, Gan, Li, Goate, Alison M, Temple, Sally, and Tau Consortium Stem Cell Group

Subjects
Aging, induced pluripotent stem cells, Neurogenesis, Clinical Sciences, tau Proteins, neural progenitor cells, Neurodegenerative, Regenerative Medicine, Alzheimer's Disease, frontotemporal dementia, Cell Line, Rare Diseases, Neural Stem Cells, Clinical Research, fibroblasts, mental disorders, MAPT, Genetics, Acquired Cognitive Impairment, Humans, 2.1 Biological and endogenous factors, tau, Genetic Testing, Aetiology, CRISPR/Cas9, Alzheimer's Disease Related Dementias (ADRD), Neurons, Gene Editing, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Induced Pluripotent Stem Cell - Human, tauopathy, Pick's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), progressive supranuclear palsy, Stem Cell Research, Brain Disorders, Frontotemporal Dementia (FTD), Tauopathies, Tau Consortium Stem Cell Group, Mutation, Neurological, Dementia, Biochemistry and Cell Biology, corticobasal degeneration
Abstract

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies.

Published
2019

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