X-linked hydrocephalus genes: Their proximity to telomeres and high A + T content compared to Parkinson's disease

Hart, Madeline; Conrad, Joshua; Barrett, Emma; Legg, Kaitlyn; Ivey, Gabrielle; Lee, Peter H.U.; Yung, Yun C.; Shim, Joon W.

doi:10.1016/j.expneurol.2023.114433

Cited by 4 publications

(3 citation statements)

References 139 publications

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“…Our prior studies on two factors of proximity to telomeres and high A + T content associated with genetics and epigenetics of human diseases ( Lucas et al, 2021 ; McKnight et al, 2021 ; Raines et al, 2022 ; White et al, 2022 ; Hart et al, 2023 ; McKnight et al, 2023 ) suggest that G protein coupled receptors harbor a positive correlation with the full-length nucleotide size ( Raines et al, 2022 ). The result presented herein regarding two factors associated with high mutation rates in mice, rats, chimpanzees, and humans indicates that GLP-1R is an exception during evolution across mice (1,480 bp, 44%) and chimpanzees (16,610 bp, 57%), i.e., A + T contents of GLP-1R in four species are less than 59%, the average of human chromosomes.…”

Section: Discussionmentioning

confidence: 99%

Reduced GLP-1R availability in the caudate nucleus with Alzheimer’s disease

Barrett,

Ivey,

Cunningham

et al. 2024

Front. Aging Neurosci.

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The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to the treatment of neurodegenerative conditions, with a particular focus on Alzheimer’s disease (AD). However, the mechanism that underlies regulation of GLP-1R availability in the brain with AD remains poorly understood. Here, using whole transcriptome RNA-Seq of the human postmortem caudate nucleus with AD and chronic hydrocephalus (CH) in the elderly, we found that GLP-1R and select mRNAs expressed in glucose dysmetabolism and dyslipidemia were significantly altered. Furthermore, we detected human RNA indicating a deficiency in doublecortin (DCX) levels and the presence of ferroptosis in the caudate nucleus impacted by AD. Using the genome data viewer, we assessed mutability of GLP-1R and 39 other genes by two factors associated with high mutation rates in chromosomes of four species. Surprisingly, we identified that nucleotide sizes of GLP-1R transcript exceptionally differed in all four species of humans, chimpanzees, rats, and mice by up to 6-fold. Taken together, the protein network database analysis suggests that reduced GLP-1R in the aged human brain is associated with glucose dysmetabolism, ferroptosis, and reduced DCX+ neurons, that may contribute to AD.

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Section: Discussionmentioning

confidence: 99%

Reduced GLP-1R availability in the caudate nucleus with Alzheimer’s disease

Barrett,

Ivey,

Cunningham

et al. 2024

Front. Aging Neurosci.

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“…Shorter TL is also clearly tied to an increased risk for cardiovascular diseases 17 , type 2 diabetes 18 , and AD 19 . Regarding the genetic contribution to the development of congenital hydrocephalus, it suggests that X-linked hydrocephalus genes are associated with congenital hydrocephalus, and these genes with a high mutation rate are associated with proximity to telomeres and high adenine and thymine content 20 . More than 100 genes are reported to be capable of causing congenital hydrocephalus, for example, the zinc finger CCHC-type domain containing 8 protein (ZCCHC8), which is located in close vicinity of its telomere (< 50 Mbp) on chromosome 12 21 .…”

Section: Introductionmentioning

confidence: 99%

The impact of telomere length on the risk of idiopathic normal pressure hydrocephalus: a bidirectional Mendelian randomization study

Wang,

Zuo,

et al. 2024

Sci Rep

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Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447–0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327–0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996–1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.

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“…Our prior studies on two factors of proximity to telomeres and high A + T content associated with genetics and epigenetics of human diseases (Lucas et al, 2021;McKnight et al, 2021;Raines et al, 2022;White et al, 2022;Hart et al, 2023;McKnight et al, 2023) suggest that G protein coupled receptors harbor a positive correlation with the fulllength nucleotide size (Raines et al, 2022). The result presented herein regarding two factors associated with high mutation rates in mice, rats, chimpanzees, and humans indicates that GLP-1R is an exception during evolution across mice (1,480 bp, 44%) and chimpanzees (16,610 bp, 57%), i.e., A + T contents of GLP-1R in four species are less than 59%, the average of human chromosomes.…”

Section: Discussionmentioning

confidence: 99%

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X-linked hydrocephalus genes: Their proximity to telomeres and high A + T content compared to Parkinson's disease

Cited by 4 publications

References 139 publications

Reduced GLP-1R availability in the caudate nucleus with Alzheimer’s disease

Reduced GLP-1R availability in the caudate nucleus with Alzheimer’s disease

The impact of telomere length on the risk of idiopathic normal pressure hydrocephalus: a bidirectional Mendelian randomization study

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