Genes and genetics in eye diseases: a genomic medicine approach for investigating hereditary and inflammatory ocular disorders

Past 25 y have witnessed an exponential increase in knowledge and understanding of ocular diseases and their respective genetic underpinnings. As a result, scientists have mapped many genes and their variants that can influence vision and health of our eyes. Based on these findings, it is becoming clear that an early diagnosis employing genetic testing can help evaluate patients＇ conditions for instituting treatment plan（s） and follow-up care to avoid vision complications later. For example, knowing family history becomes crucial for inherited eye diseases as it can benefit members in family who may have similar eye diseases or predispositions. Therefore, gathering information from an elaborate examination along with complete assessment of past medical illness by ophthalmologists followed by consultation with geneticists can help create a roadmap for making diagnosis and treatment precise and beneficial. In this review, we present an update on ocular genomic medicine that we believe has tremendous potential towards unraveling genetic implications in ocular diseases and patients＇ susceptibilities. We also discuss translational aspects of genetic ophthalmology and genome engineering that may help advance molecular diagnostics and therapeutics.

An everlasting role of genetics and genomics in public health: a meeting report of ACGA-HKSMG International Conference on Genetic and Genomic Medicine 2008

The Association of Chinese Geneticists in America （ACGA） and the Hong Kong Society of Medical Genetics （HKSMG） held their first joint Conference on Genetic and Genomic Medicine in Hong Kong from June 9-11 in 2008 at the Cheung Kung Hai Conference Center, William MW Mong Block, Li Ka Shing Faculty of Medicine, the University of Hong Kong. Other co-organizers included the University of Hong Kong and Chinese Society of Medical Genetics. A satellite conference ＂ACGA-WZMC International Symposium of Genetics and Translational Medicine＂, co-organized with Wenzhou Medical College and Chinese Society of Medical Genetics, was held from June 12-14, 2008 at Wenzhou, Zhejiang Province of China.

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.

Medical genetics:Towards precision medicine

Medical genetics is defined as a branch of medicine that involves the diagnosis and management of hereditary disorders by applying genetics to medical care.The Human Genome Project,initiated in1990 and completed in 2004,has profoundly changed biology and is rapidly catalyzing a transformation of medical genetics and medicine in general（Collins and McKusick,2001;Green and Guyer,2011）.

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive response.We previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq.The AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT transcription.The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related phenotypes.Methods We used in silico,in vitro,in vivo,and retrospective models to test this hypothesis.Results In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT mRNA.Unexpectedly,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model.Genotype-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>T.However,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with HTN.Conclusions We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White participants.Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>G.Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Precision medicine in hearing loss

Precision medicine（PM） proposes customized medical care based on a patient＇s unique genome, biomarkers, environment and behaviors. Hearing loss（HL） is the most common sensorineural disorder worldwide and is frequently caused by a single genetic mutation. With recent advances in PM tools such as genetic sequencing and data analysis, the field of HL is ideally positioned to adopt the strategies of PM.Here, we review current and future applications of PM in HL as they relate to the four core qualities of PM（P4）： predictive, personalized, patient-centered, and participatory. We then introduce a strategy for effective incorporation of HL PM into the design of future research studies, electronic medical records,and clinical practice to improve diagnostics, prognostics, and, ultimately, individualized patient treatment. Finally, specific anticipated ethical and economic concerns in this growing era of genomics-based HL treatment are discussed. By integrating PM principles into translational HL research and clinical practice, hearing specialists are uniquely positioned to effectively treat the heterogeneous causes and manifestations of HL on an individualized basis.