An Update on Phosphodiesterase Mutations Underlying Genetic Etiology of Hearing Loss and Retinitis Pigmentosa

Mittal, Rahul; Bencie, Nicole; Parrish, James M.; Liu, George; Mittal, Jeenu; Yan, Denise; Liu, Xue Zhong

doi:10.3389/fgene.2018.00009

Cited by 17 publications

(20 citation statements)

References 26 publications

(32 reference statements)

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“…The significance of these observations remains unclear, but suggests a more complex co-regulation at the chromosome 11 locus. Although we cannot separate CYP2R1 from PDE3B and RRAS2 using the results from the eQTL comparison analysis, our data together with previously published studies collectively suggest that CYP2R1 is the gene behind the observed GWA signal for 25(OH)D in the chromosome 11 locus [14,16,17,[19][20][21]28].…”

Section: Comparing Association Signals With Gene Expression Datacontrasting

confidence: 47%

“…These 9 studies reported in total 47 independent SNPs (41 unique SNPs) that were associated with 25(OH)D levels on a genome wide significant level ( Fig 2). The two signals identified in our study are located within the two strongest previously known loci for 25(OH)D concentrations, most often mapped to the genes GC and CYP2R1 [14,16,17,[19][20][21]. However, in a pediatric setting, the GWAS catalog only reports one previous GWA-study on 25(OH)D, involving children aged �6 years, that has been able to find genomewide significant loci [20].…”

Section: Two Genome-wide Significant Loci Near the Genes Gc And Cyp2r1mentioning

confidence: 72%

“…Both these two loci have in previous GWA studies been shown to associate with serum 25(OH)D but no GWA data exist for children as young as our cohort. We identified in the GWAS catalog 9 separate studies using 25(OH)D concentration as the studied trait (accessed September 2019) [14][15][16][17][18][19][20][21][22][23]. These 9 studies reported in total 47 independent SNPs (41 unique SNPs) that were associated with 25(OH)D levels on a genome wide significant level ( Fig 2).…”

Section: Two Genome-wide Significant Loci Near the Genes Gc And Cyp2r1mentioning

confidence: 99%

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Genetic variation in GC and CYP2R1 affects 25-hydroxyvitamin D concentration and skeletal parameters: A genome-wide association study in 24-month-old Finnish children

Kämpe

Enlund-Cerullo

Valkama

et al. 2020

ESPE

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Vitamin D is important for normal skeletal homeostasis, especially in growing children. There are no previous genome-wide association (GWA) studies exploring genetic factors that influence vitamin D metabolism in early childhood. We performed a GWA study on serum 25hydroxyvitamin D (25(OH)D) and response to supplementation in 761 healthy term-born Finnish 24-month-old children, who participated in a randomized clinical trial comparing effects of 10 μg and 30 μg of daily vitamin D supplementation from age 2 weeks to 24 months. Using the Illumina Infinium Global Screening Array, which has been optimized for imputation, a total of 686085 markers were genotyped across the genome. Serum 25(OH)D was measured at the end of the intervention at 24 months of age. Skeletal parameters reflecting bone strength were determined at the distal tibia at 24 months using peripheral quantitative computed tomography (pQCT) (data available for 648 children). For 25(OH)D, two strong GWA signals were identified, localizing to GC (Vitamin D binding protein) and CYP2R1 (Vitamin D 25hydroxylase) genes. The GWA locus comprising the GC gene also associated with response to supplementation. Further evidence for the importance of these two genes was obtained by comparing association signals to gene expression data from the Genotype-Tissue Expression project and performing colocalization analyses. Through the identification of haplotypes associated with low or high 25(OH)D concentrations we used a Mendelian randomization approach to show that haplotypes associating with low 25(OH)D were also associated with low pQCT parameters in the 24-month-old children. In this first GWA study on 25(OH)D in this age group we show that already at the age of 24 months genetic variation influences 25(OH)D concentrations and determines response to supplementation, with genome-wide significant associations with GC and CYP2R1. Also, the dual association between haplotypes, 25(OH)D and pQCT parameters gives support for vertical pleiotropy mediated by 25(OH)D.

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Section: Comparing Association Signals With Gene Expression Datacontrasting

confidence: 47%

Section: Two Genome-wide Significant Loci Near the Genes Gc And Cyp2r1mentioning

confidence: 72%

Section: Two Genome-wide Significant Loci Near the Genes Gc And Cyp2r1mentioning

confidence: 99%

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Genetic variation in GC and CYP2R1 affects 25-hydroxyvitamin D concentration and skeletal parameters: A genome-wide association study in 24-month-old Finnish children

Kämpe

Enlund-Cerullo

Valkama

et al. 2020

ESPE

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“…These native breed generally show high levels of phenotypic variation [3][4][5][6][7] and are better adapted to local environments than specialised dairy and beef breeds, which are mostly of European taurine origin [8][9][10]. Indigenous populations have been reported for the major livestock species, including sheep, goat, pig, and cattle [7,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

A genetically unique Chinese cattle population shows evidence of common ancestry with wild species when analysed with a reduced ascertainment bias SNP panel

et al. 2020

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In Hong Kong, there is a cattle population of~1,200 individuals of uncertain origin and genetic diversity. This population shows heterogeneous morphology, both in body type and pigmentation. Once used as draught animals by the local farmers, they were abandoned around the 1970s due to changes in the economy, and since then have lived as feral populations. To explore the origins of these cattle, we analysed~50k genotype data of 21 Hong Kong feral cattle, along with data from 703 individuals of 36 cattle populations of European, African taurine, and Asian origin, the wild x domestic hybrid gayal, plus two wild bovine species, gaur and banteng. To reduce the effect of ascertainment bias~4k loci that are polymorphic in the two wild species were selected for further analysis. The stringent SNP selection we applied resulted in increased heterozygosity across all populations studies, compared with the full panel of SNP, thus reducing the impact of ascertainment bias and facilitating the comparison of divergent breeds of cattle. Our results showed that Hong Kong feral cattle have relatively high levels of genetic distinctiveness, possibly due to the low level of artificial selection, and a likely common ancestry with wild species. We found signs of a putative taurine introgression, probably dating to the import of north European breeds during the British colonialism of Hong Kong. We showed that Hong Kong feral cattle, are distinct from Bos taurus and Bos indicus breeds. Our results highlight the distinctiveness of Hong Kong feral cattle and stress the conservation value of this indigenous breed that is likely to harbour adaptive genetic variation, which is a fundamental livestock resource in the face of climate change and diversifying market demands.

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“…Furthermore, altered levels of 14-3-3 proteins were found in the blood or brains of patients with ASD [ 29 , 43 , 44 ], schizophrenia [ 45 , 46 , 47 , 48 ] and bipolar disorder [ 48 ]. Interestingly, microduplications of YWHAE, which encodes 14-3-3ε that form stable heterodimers with 14-3-3ζ, were reported in ASD patients; whereas microdeletions involving both YWHAE and PAFAH1B1 genes cause Miller–Dieker syndrome, a form of lissencephaly with ID and seizures [ 49 , 50 , 51 , 52 , 53 ], and deletions including YWHAG and HIP1 were related to epilepsy, learning problems and ID [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses

Torrico

Antón-Galindo

Fernàndez‐Castillo

et al. 2020

JCM

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The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the: (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders; (iii) burden of rare variants in ASD and schizophrenia; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10−7), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia.

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An Update on Phosphodiesterase Mutations Underlying Genetic Etiology of Hearing Loss and Retinitis Pigmentosa

Cited by 17 publications

References 26 publications

Genetic variation in GC and CYP2R1 affects 25-hydroxyvitamin D concentration and skeletal parameters: A genome-wide association study in 24-month-old Finnish children

Genetic variation in GC and CYP2R1 affects 25-hydroxyvitamin D concentration and skeletal parameters: A genome-wide association study in 24-month-old Finnish children

A genetically unique Chinese cattle population shows evidence of common ancestry with wild species when analysed with a reduced ascertainment bias SNP panel

Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses

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