Genetics in Ophthalmology

Clinical Diagnostic ◽

На сегодняшний день в базе данных Online Mendelian Inheritance in Man (OMIM) описано более 6613 заболеваний и фенотипов, 4241 имеют доказанную генетическую основу, не менее 45% вкючают офтальмологические проявления. В статье приведен ряд клинический примеров пациентов с офтальмологическими симптомами различных генетических заболеваний (алкаптонурия, болезнь Штаргардта, синдром микроцефалии с или без хориоретинопатии; астроцитарная гамартома) с целью демонстрации эффективного клинико-диагностического скрининга генетической патологии у пациентов. So far, the Online Mendelian Inheritance in Man (OMIM) database describes more than 6613 diseases and phenotypes, 4241 have a proven genetic basis, 45% of which are combined with ophthalmological manifestations. The article provides a number of clinical examples of patients with ophthalmological manifestations of various genetic diseases (alcaptonuria, Stadgart ‘s disease, microcephaly syndrome with or without choriretinopathy; Astrocytic gamartoma) to demonstrate effective clinical-diagnostic screening of genetic pathology in patients.

An integrative, translational approach to understanding rare and orphan genetically based diseases

Interface Focus ◽

10.1098/rsfs.2012.0055 ◽

2013 ◽

Vol 3 (2) ◽

pp. 20120055 ◽

Cited By ~ 13

Author(s):

Robert Hoehndorf ◽

Paul N. Schofield ◽

Georgios V. Gkoutos

Keyword(s):

Animal Model ◽

Candidate Genes ◽

Molecular Basis ◽

Genetic Diseases ◽

Clinical Signs ◽

Mendelian Inheritance ◽

Disease Phenotypes ◽

Guilt By Association ◽

Translational Approach ◽

PhenomeNet is an approach for integrating phenotypes across species and identifying candidate genes for genetic diseases based on the similarity between a disease and animal model phenotypes. In contrast to ‘guilt-by-association’ approaches, PhenomeNet relies exclusively on the comparison of phenotypes to suggest candidate genes, and can, therefore, be applied to study the molecular basis of rare and orphan diseases for which the molecular basis is unknown. In addition to disease phenotypes from the Online Mendelian Inheritance in Man (OMIM) database, we have now integrated the clinical signs from Orphanet into PhenomeNet. We demonstrate that our approach can efficiently identify known candidate genes for genetic diseases in Orphanet and OMIM. Furthermore, we find evidence that mutations in the HIP1 gene might cause Bassoe syndrome, a rare disorder with unknown genetic aetiology. Our results demonstrate that integration and computational analysis of human disease and animal model phenotypes using PhenomeNet has the potential to reveal novel insights into the pathobiology underlying genetic diseases.

Corrections to: "Phenotypic and Genotypic Analyses of Genetic Skin Disease through the Online Mendelian Inheritance in Man (OMIM) Database"

Journal of Investigative Dermatology ◽

10.1038/jid.2009.363 ◽

2010 ◽

Vol 130 (3) ◽

pp. 909-910

Keyword(s):

Skin Disease ◽

Mendelian Inheritance ◽

Phenotypic and Genotypic Analyses of Genetic Skin Disease through the Online Mendelian Inheritance in Man (OMIM) Database

Journal of Investigative Dermatology ◽

10.1038/jid.2009.108 ◽

2009 ◽

Vol 129 (11) ◽

pp. 2628-2636 ◽

Cited By ~ 40

Author(s):

Jamison D. Feramisco ◽

Ruslan I. Sadreyev ◽

Mitzi L. Murray ◽

Nick V. Grishin ◽

Hensin Tsao

Keyword(s):

Skin Disease ◽

Mendelian Inheritance ◽

A Diagnostic Case Study of a Young Man with Russell-Silver Syndrome and Associated Comorbidities

Asian Journal of Interdisciplinary Research ◽

10.34256/ajir1912 ◽

2019 ◽

Vol 2 (1) ◽

pp. 12-29

Author(s):

Boon Hock Lim ◽

Ban Meng Lee ◽

Benjamin Kee Kee Ern Lim ◽

Guo Hui XIE

Keyword(s):

Response To Intervention ◽

Mendelian Inheritance ◽

Diagnostic Information ◽

Silver Syndrome

This is a case study of a young man diagnosed with Russell-Silver Syndrome or RSS for short (Online Mendelian Inheritance in Man® Classification Number #180860) and associated comorbidities. The aim of this paper is to provide diagnostic information about the syndrome with its comorbidities so that educational therapists and other allied professionals working with such individuals will know what to look out for, especially the RSS-associated comorbidities, and in that way, they become better informed in order to know what offer in their Response to Intervention (RtI) for such individuals with RSS.

Epistatic Control of Non-Mendelian Inheritance in Mouse Interspecific Crosses

Genetics ◽

10.1093/genetics/143.4.1739 ◽

1996 ◽

Vol 143 (4) ◽

pp. 1739-1752 ◽

Cited By ~ 2

Author(s):

Xavier Montagutelli ◽

Rowena Turner ◽

Joseph H Nadeau

Keyword(s):

X Chromosome ◽

Genetic Basis ◽

Mendelian Inheritance ◽

The Other ◽

Interspecific Crosses ◽

Chromosome 2 ◽

Mus Spretus ◽

F1 Hybrid ◽

Strong Deviation ◽

Marker Loci

Abstract Strong deviation of allele frequencies from Mendelian inheritance favoring Mus spretus-derived alleles has been described previously for X-linked loci in four mouse interspecific crosses. We reanalyzed data for three of these crosses focusing on the location of the gene(s) controlling deviation on the X chromosome and the genetic basis for incomplete deviation. At least two loci control deviation on the X chromosome, one near Xist (the candidate gene controlling X inactivation) and the other more centromerically located. In all three crosses, strong epistasis was found between loci near Xist and marker loci on the central portion of chromosome 2. The mechanism for this deviation from Mendelian expectations is not yet known but it is probably based on lethality of embryos carrying particular combinations of alleles rather than true segregation distortion during oogenesis in F1 hybrid females.

Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130)

Cells ◽

10.3390/cells10030590 ◽

2021 ◽

Vol 10 (3) ◽

pp. 590

Author(s):

Paula I. Metselaar ◽

Celine Hos ◽

Olaf Welting ◽

Jos A. Bosch ◽

Aletta D. Kraneveld ◽

...

Keyword(s):

Immune System ◽

Histone Deacetylase ◽

Mendelian Inheritance ◽

Splicing Factor ◽

Lectin Receptor ◽

Corepressor Complex ◽

A Subunit

In 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as ‘SAP130, a subunit of the histone deacetylase complex.’ However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3). This splicing factor is unrelated to SAP130 (Sin3A associated protein 130, a subunit of the histone deacetylase-dependent Sin3A corepressor complex). The conclusions in the three articles were formulated for SF3B3, while the researchers used qPCR primers and antibodies against SAP130. We retraced the origins of the ambiguity about the two proteins and found that Online Mendelian Inheritance in Man (OMIM) added a Nature publication on SF3B3 as a reference for Sin3A associated protein 130 in 2016. Subsequently, companies such as Abcam referred to OMIM and the Nature article in their products for both SF3B3 and SAP130. In turn, the mistake by OMIM followed in the persistent and confusing use of ‘SAP130′ (spliceosome-associated protein 130) as an alternative symbol for SF3B3. With this report, we aim to eliminate the persistent confusion and separate the literature regarding the two proteins.

Ciliary Signalling and Mechanotransduction in the Pathophysiology of Craniosynostosis

Genes ◽

10.3390/genes12071073 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1073

Author(s):

Federica Tiberio ◽

Ornella Parolini ◽

Wanda Lattanzi

Keyword(s):

Primary Cilium ◽

Genetic Basis ◽

Mendelian Inheritance ◽

Craniofacial Development ◽

Cranial Sutures ◽

Craniofacial Malformation ◽

Computational Annotation ◽

Neural Crest Origin ◽

Disease Associated Genes ◽

Molecular Signals

Craniosynostosis (CS) is the second most prevalent inborn craniofacial malformation; it results from the premature fusion of cranial sutures and leads to dimorphisms of variable severity. CS is clinically heterogeneous, as it can be either a sporadic isolated defect, more frequently, or part of a syndromic phenotype with mendelian inheritance. The genetic basis of CS is also extremely heterogeneous, with nearly a hundred genes associated so far, mostly mutated in syndromic forms. Several genes can be categorised within partially overlapping pathways, including those causing defects of the primary cilium. The primary cilium is a cellular antenna serving as a signalling hub implicated in mechanotransduction, housing key molecular signals expressed on the ciliary membrane and in the cilioplasm. This mechanical property mediated by the primary cilium may also represent a cue to understand the pathophysiology of non-syndromic CS. In this review, we aimed to highlight the implication of the primary cilium components and active signalling in CS pathophysiology, dissecting their biological functions in craniofacial development and in suture biomechanics. Through an in-depth revision of the literature and computational annotation of disease-associated genes we categorised 18 ciliary genes involved in CS aetiology. Interestingly, a prevalent implication of midline sutures is observed in CS ciliopathies, possibly explained by the specific neural crest origin of the frontal bone.

Interval mapping of viability loci causing heterosis in Arabidopsis.

Genetics ◽

10.1093/genetics/140.3.1105 ◽

1995 ◽

Vol 140 (3) ◽

pp. 1105-1109

Author(s):

T Mitchell-Olds

Keyword(s):

Genetic Basis ◽

Chromosomal Region ◽

Empirical Studies ◽

Genetic Diseases ◽

Short Interval ◽

Interval Mapping ◽

Hybrid Vigor ◽

Breeding Systems ◽

Mapping Procedure ◽

Chromosome I

Abstract The genetic basis of heterosis has implications for many problems in genetics and evolution. Heterosis and inbreeding depression affect human genetic diseases, maintenance of genetic variation, evolution of breeding systems, agricultural productivity, and conservation biology. Despite decades of theoretical and empirical studies, the genetic basis of heterosis has remained unclear. I mapped viability loci contributing to heterosis in Arabidopsis. An overdominant factor with large effects on viability mapped to a short interval on chromosome I. Homozygotes had 50% lower viability than heterozygotes in this chromosomal region. Statistical analysis of viability data in this cross indicates that observed viability heterosis is better explained by functional overdominance than by pseudo-overdominance. Overdominance sometimes may be an important cause of hybrid vigor, especially in habitually inbreeding species. Finally, I developed a maximum likelihood interval mapping procedure that can be used to examine chromosomal regions showing segregation distortion or viability selection.