Development and evaluations of the ancestry informative markers of the VISAGE Enhanced Tool for Appearance and Ancestry.

The VISAGE Enhanced Tool for Appearance and Ancestry (ET) has been designed to combine markers for the prediction of bio-geographical ancestry plus a range of externally visible characteristics into a single massively parallel sequencing (MPS) assay. We describe the development of the ancestry panel markers used in ET, and the enhanced analyses they provide compared to previous MPS-based forensic ancestry assays. As well as established autosomal single nucleotide polymorphisms (SNPs) that differentiate sub-Saharan African, European, East Asian, South Asian, Native American, and Oceanian populations, ET includes autosomal SNPs able to efficiently differentiate populations from Middle East regions. The ability of the ET autosomal ancestry SNPs to distinguish Middle East populations from other continentally defined population groups is such that characteristic patterns for this region can be discerned in genetic cluster analysis using STRUCTURE. Joint cluster membership estimates showing individual co-ancestry that signals North African or East African origins were detected, or cluster patterns were seen that indicate origins from central and Eastern regions of the Middle East. In addition to an augmented panel of autosomal SNPs, ET includes panels of 85 Y-SNPs, 16 X-SNPs and 21 autosomal Microhaplotypes. The Y- and X-SNPs provide a distinct method for obtaining extra detail about co-ancestry patterns identified in males with admixed backgrounds. This study used the 1000 Genomes admixed African and admixed American sample sets to fully explore these enhancements to the analysis of individual co-ancestry. Samples from urban and rural Brazil with contrasting distributions of African, European, and Native American co-ancestry were also studied to gauge the efficiency of combining Y- and X-SNP data for this purpose. The small panel of Microhaplotypes incorporated in ET were selected because they showed the highest levels of haplotype diversity amongst the seven population groups we sought to differentiate. Microhaplotype data was not formally combined with single-site SNP genotypes to analyse ancestry. However, the haplotype sequence reads obtained with ET from these loci creates an effective system for de-convoluting two-contributor mixed DNA. We made simple mixture experiments to demonstrate that when the contributors have different ancestries and the mixture ratios are imbalanced (i.e., not 1:1 mixtures) the ET Microhaplotype panel is an informative system to infer ancestry when this differs between the contributors.

Causes of childhood blindness in a school for the visually impaired in Hong Kong.

OBJECTIVE: To identify the causes of blindness in children attending a school for the blind in Hong Kong. DESIGN: Cross-sectional observational study. SETTING: School for blind children in Hong Kong. PARTICIPANTS: Eighty-two blind students at the Ebenezer School and Home for the Visually Impaired were examined between December 1998 and August 1999. MAIN OUTCOME MEASURES: Demographic data were obtained from students and a questionnaire assessment made of their medical and ocular history. Visual acuity was assessed and visual loss classified according to the World Health Organization classification of visual impairment. Complete ophthalmic assessments were performed in all students including slit-lamp examination and dilated binocular indirect ophthalmoscopy. RESULTS: The mean age of the students was 12.2 years. Ten (12.2%) had a family history of eye disease. Major past medical illnesses were reported in 50% with prematurity and diseases of the central nervous system found in 26.8% and 11.0% of students, respectively. The most common anatomical site for visual impairment was the retina (47.6%), followed by diseases of the optic nerve (14.6%), and diseases of the anterior segment and the lens (14.6%). CONCLUSIONS: The pattern of childhood blindness in Hong Kong is similar to that seen in other developed countries. Preventable causes of childhood blindness, such as prematurity and birth asphyxia, were responsible for a large proportion of cases. Early diagnosis and treatment of such conditions may reduce the incidence of childhood blindness in Hong Kong.

Astigmatism in Chinese preschool children: prevalence, change, and effect on refractive development.

AIM: To study the prevalence, type, and progression of astigmatism in Chinese preschool children, and its effect on refractive development. METHODS: A cross sectional study of preschool children was carried out in two randomly selected kindergartens. A cohort study was performed on a subset of children, five years after initial examination. Refractive error (measured by cycloplegic autorefraction) and axial ocular dimensions (measured by ultrasonography) were the main study outcomes. RESULTS: 522 children participated in the study; the mean age was 55.7 months (SD 10.9; range 27 to 77). Mean cylinder reading was -0.65 D (SD 0.58; range 0.00 to -4.75), and with the rule astigmatism was predominant (53%). In the 108 children studied longitudinally, the mean cylinder reading reduced from -0.62 D to -0.50 D (p = 0.019). The presence of astigmatism in initial examination predisposed the eyes towards greater myopisation (p<0.001). In addition, children with increased astigmatism had greater myopic progression (p<0.001) and axial length growth (p = 0.002). CONCLUSIONS: This study reports a high prevalence of astigmatism in Chinese preschool children. The presence of astigmatism, and particularly with increasing astigmatism, appears to predispose the children to progressive myopia. Further studies are warranted.

Myopia progression among preschool Chinese children in Hong Kong.

INTRODUCTION: Myopia is the most common eye disorder especially in Asia. However, the information on myopic progression and ocular growth among preschool children, who undergo rapid changes, is limited. The aim of this study was to determine the prevalence, incidence of myopia and myopic progression among preschool children in Hong Kong. MATERIALS AND METHODS: A kindergarten was randomly chosen in Hong Kong, China. Preschool children aged 2 to 6 years attending the selected kindergarten were invited to participate. One hundred and eight children completed the 5-year cohort study. Refractive error and axial ocular dimensions were the main outcome measures. RESULTS: A total of 255 preschool children with a mean age of 4.96 (SD, 0.90) years were examined in the initial examination. Only 4.6% children had myopia of at least -0.50 D. The prevalence of myopia increased almost 10-fold to 43.5% after 5 years in the final examination. The annual incidence of myopia was 8.2%. The mean increase in axial length was 1.72 mm (SD, 0.80 mm) over the 5-year period (P < 0.001). The lens thickness decreased significantly from 3.80 mm (SD, 0.37 mm) to 3.74 mm (SD, 0.51 mm) whereas the vitreous chamber depth increased significantly from 15.01 mm (SD, 0.68 mm) to 16.42 mm (SD, 0.88 mm) (both P < 0.001). Children who were younger or were less hypermetropic at the initial examination was having greater myopic progression (P = 0.015, P < 0.001 respectively). CONCLUSION: This is the first prospective study to investigate the myopic progression and ocular growth among preschool children. Hong Kong has a high prevalence of myopia even in preschool children. They also experience a significant myopic shift and ocular growth. Further studies on the prevention of myopic development or progression should be targeted on this population.