Genotype–phenotype associations and human eye color

White, Désirée; Rabago-Smith, Montserrat

doi:10.1038/jhg.2010.126

Cited by 88 publications

(46 citation statements)

References 27 publications

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“…This may suggest a shared promoter or some unknown transcriptional mechanisms involving the GABRB3 exon 1–3 region that is critical for Oca2 gene expression. It has also been previously reported that an intron in HERC2 contains the promoter region for Oca2 , suggesting complex transcriptional regulation of Oca2 by its adjacent genes (White and Rabago-Smith, 2011). The GABRB3 promoter region is critical for transcriptional factor binding (Tanaka et al, 2012a) and splicing as previously demonstrated (Kirkness and Fraser, 1993).…”

Section: Discussionmentioning

confidence: 69%

Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation

Delahanty¹,

Zhang²,

Bichell³

et al. 2016

Cell Reports

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Reduced ocular pigmentation is common in Angelman syndrome (AS) and Prader-Willi syndrome (PWS) and long thought to be caused by OCA2 deletion. GABRB3 is located in the 15q11-13 region flanked by UBE3A, GABRA5, GABRG3 and OCA2. Mutations in GABRB3 have been frequently associated with epilepsy and autism, consistent with its role in neurodevelopment. We report here a robust phenotype in the mouse in which deletion of Gabrb3 alone causes nearly complete loss of retinal pigmentation due to atrophied melanosomes, as evidenced by electron microscopy. Using exome and RNA sequencing, we confirmed that only the Gabrb3 gene was disrupted while the Oca2 gene was intact. However, mRNA abundance of Oca2 and other genes adjacent to Gabrb3 is substantially reduced in Gabrb3−/− mice, suggesting complex transcriptional regulation in this region. These results suggest that impairment in GABRB3 downregulates OCA2 and indirectly causes ocular hypopigmentation and visual defects in AS and PWS.

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Section: Discussionmentioning

confidence: 69%

Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation

Delahanty¹,

Zhang²,

Bichell³

et al. 2016

Cell Reports

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“…The haplotypes of this region were previously suggested to increase eye colour prediction [6,20,5]. It was suggested [12,21] that the OCA2 allele rs1800407 A decreased the pigmentation level in the eye when found in cis phase with the HERC2 allele rs12913832 A, whereas the OCA2 allele rs1800407 A found in Page 11 of 23 A c c e p t e d M a n u s c r i p t cis phase with the HERC2 allele rs12913832 G will display little effect on the eye colour because the transcription of OCA2 is reduced.…”

Section: The Predictive Properties Of the Irisplex Prediction Modelmentioning

confidence: 99%

The effect of gender on eye colour variation in European populations and an evaluation of the IrisPlex prediction model

Pietroni

Andersen

Johansen

et al. 2014

Forensic Science International: Genetics

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In this study, we investigate the role of gender as a factor that contributes to eye colour variation and suggest that the gender effect on eye colour is population specific.A total of 230 Italian individuals were typed for the six IrisPlex SNPs (rs12913832, rs1800407, rs12896399, rs1393350, rs16891982 and rs12203592). A quantitative eye colour score (Pixel Index of the Eye: PIE-score) was calculated based on digital eye images using the custom made DIAT software. The results were compared with those of Danish and Swedish population samples.As expected, we found HERC2 rs12913832 as the main predictor of human eye colour independently of ancestry. Furthermore, we found gender to be significantly associated with quantitative eye colour measurements in the Italian population sample. We found that the association was statistically significant only among Italian individuals typed as heterozygote GA for HERC2 rs12913832. Interestingly, we did not observe the same association in the Danish and Swedish population. This indicated that the gender effect on eye colour is population specific. We estimated the effect of gender on quantitative eye colour in the Italian population sample to be 4.9%. Among gender and the IrisPlex SNPs, gender ranked as the second most important predictor of human eye colour variation in Italians after HERC2 rs12913832. We, furthermore, tested the five lower ranked IrisPlex predictors, and evaluated all possible 3 6 (729) genotype combinations of the IrisPlex assay and their corresponding predictive values using the IrisPlex prediction model [4]. The results suggested that maximum three (rs12913832, rs1800407, rs16891982) of the six IrisPlex SNPs are useful in practical forensic genetic casework.

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“…HERC1 has been implicated in membrane trafficking and cell proliferation/growth through its interactions with the ARF, Rab, clathrin, M2-pyruvate kinase, and TSC2 proteins (20 -23). HERC2 is one of two major genes responsible for eye color in humans (24). Several radiation and ethylnitrosourea-induced mutations at the mouse Herc2 locus cause neuromuscular tremor, runting, juvenile lethality, and sperm defects (25)(26)(27).…”

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confidence: 99%