Genome-wide analysis of methylation in giant pandas with cataract by methylation-dependent restriction-site associated DNA sequencing (MethylRAD)

You, Yuyan; Bai, Chao; Li, Xuefeng; Xia, Maohua; Jia, Ting; Li, Xiaoguang; Zhang, Chenglin; Chen, Yucun; Zhao, Shanshan; Wang, Liqin; Wang, Wei; Yin, Yanqiang; Xiu, Yunfang; Niu, Lili; Zhou, Jun; Ma, Tao; Du, Yang; Liu, Qing

doi:10.1371/journal.pone.0222292

Cited by 11 publications

(13 citation statements)

References 34 publications

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“…Although genetic factors have been identified that promote age-related cataracts, the most important triggers are environmental, particularly oxidative stress and DNA damage [ 7 – 10 ]. We previously compared the DNA methylation status of giant pandas with and without cataracts in an attempt to identify epigenetic effects that might influence the expression of genes associated with cataract formation [ 17 ]. We identified multiple differentially methylated genes with potential roles in cataract-related pathways, including base excision repair, apoptosis and p53 signaling.…”

Section: Discussionmentioning

confidence: 99%

“…The genes most strongly associated with cataracts therefore include those related to oxidative stress responses, the production of antioxidant enzymes and metabolites, and various DNA repair pathways [ 11 – 13 ]. Previous studies identified changes in DNA methylation associated with cataract formation in several mammals [ 14 – 16 ] and we recently reported that 110 genes with functions relevant to cataract pathogenesis are differentially methylated in giant pandas, including six genes known to be associated with age-related cataracts in humans [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation

You¹,

Bai²,

Li³

et al. 2021

BMC Genom Data

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Background The giant panda (Ailuropoda melanoleuca) is an endangered mammalian species native to China. Fewer than 2500 giant pandas are known to exist, many of which are bred in captivity as a means to preserve and repopulate the species. Like other captive mammals, giant pandas acquire age-related cataracts, reducing their quality of life. Recent comparative genome-wide methylation analysis revealed 110 differentially methylated genes associated with cataract formation including six also associated with the formation of age-related cataracts in humans. Results To investigate the pathological pathway in greater detail, here we used RNA-Seq analysis to investigate the differential expression profiles of genes in three giant pandas with cataracts and three healthy controls. We identified more than 700 differentially expressed genes, 29 of which were selected for further analysis based on their low q-value. We found that many of the genes encoded regulatory and signaling proteins associated with the control of cell growth, migration, differentiation and apoptosis, supporting previous research indicating a key role for apoptosis in cataract formation. Conclusion The identification of genes involved in the formation of age-related cataracts could facilitate the development of predictive markers, preventative measures and even new therapies to improve the life of captive animals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation

You¹,

Bai²,

Li³

et al. 2021

BMC Genom Data

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“…This phenomenon has been observed in companion animals: for example, cataract development in dogs is often associated with diabetes, obesity, prolonged use of corticosteroid, excessive exposure to sunlight, or previous eye injury/inflammation [ 52 , 53 ]. It is therefore unclear whether cataracts in captive pandas are age-related acquired or congenital lesions due to the absence of suitable genetic markers [ 54 ]. Here we used a functional candidate gene screening approach to test 11 known cataract-associated genes in giant panda specimens with and without cataracts.…”

Section: Introductionmentioning

confidence: 99%

A novel missense mutation in the gene encoding major intrinsic protein (MIP) in a Giant panda with unilateral cataract formation

Bai¹,

You²,

Li³

et al. 2021

BMC Genomics

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Background Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or acquired (age-related) lesions. Results Here we used a functional candidate gene screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G > A) in the MIP gene encoding major intrinsic protein. This is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.S229N) in the C-terminal tail of the protein, and modeling predicts that the mutation induces conformational changes that may interfere with lens permeability and cell–cell interactions. Conclusion The c.686G > A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.

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“…Although mutations affecting MIP have been shown to cause congenital cataracts in humans and mice, analogous mutations have not been reported in the giant panda (Ailuropoda melanoleuca). These animals tend to develop cataracts in captivity because they live much longer than their counterparts in the wild, but it is often unclear whether these are age-related or congenital lesions due to the absence of suitable disease markers (You et al 2019). Here we used a functional candidate gene screening approach to test for known cataract-associated genes in giant panda specimens with cataracts.…”

Section: Introductionmentioning

confidence: 99%

A Novel Missense Mutation in the Gene Encoding Major Intrinsic Protein (MIP) in a Giant Panda with Cataracts

Bai¹,

You²,

Liu³

et al. 2020

Preprint

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Background : Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or sporadic (age-related) lesions.Results: Here we used a functional candidate gene-screening approach to identify mutations associated with cataracts in a captive giant panda ( Ailuropoda melanoleuca ). We identified a novel missense mutation ( c.686G>A) in the MIP gene encoding major intrinsic protein, which is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine ( p.229S>N ) in the C-terminal tail of the protein, and modeling revealed that mutation-induced conformational changes may interfere with lens permeability and cell–cell interactions.Conclusions: The mutation was not found in healthy pandas, suggesting it could serve as a new informative marker to predict the risk of congenital cataracts in captive giant pandas.

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Genome-wide analysis of methylation in giant pandas with cataract by methylation-dependent restriction-site associated DNA sequencing (MethylRAD)

Cited by 11 publications

References 34 publications

RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation

RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation

A novel missense mutation in the gene encoding major intrinsic protein (MIP) in a Giant panda with unilateral cataract formation

A Novel Missense Mutation in the Gene Encoding Major Intrinsic Protein (MIP) in a Giant Panda with Cataracts

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