EGAGenomicsIllumina Genome Analyzer II, Illumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001000127EGAEGA study EGAS00001000127UK10K_RARE_COLOBOMA REL-2012-11-27UK10K_RARE_COLOBOMA REL-2012-07-05UK10K_RARE_COLOBOMA REL-2013-04-20UK10K_RARE_COLOBOMA REL-2012-01-13UK10K_RARE_COLOBOMA REL-2012-02-22restrictedEGAOcular, Ocular Coloboma, congenital ocular coloboma, Coloboma, Choroid, coloboma of macula, Colobomas, rare (European definition), Uveoretinal Colobomas., Uveoretinal Coloboma, Uveoretinal, Ocular Colobomas, Coloboma Of Iris, And Retinaextent, Networks, Postnidation Embryo, visual_system, Antemortem Diagnosis, Disorders, Inheritance, Materials, Kinship, Pre-implantation Embryo Development, Hox-10, HOX10, Incidences, Person-time Rates, Post-implantation, Chx10, Proportion, CN-II, protein, Pre implantation Embryo Development, Diagnosis, Adiposis, Disorders Usually Diagnosed in Infancy, Embryonic Programming, CHX10, gou shu, Mutations, AEY11, Obese, Techniques, Embryo Development, Readability, unspecified, congenital ocular coloboma, xpax6, diseases, Method, AN, Uveoretinal Colobomas, eye, symptoms, Life Cycle, diseases and disorders, AW048865, globe, Incidence Rate, protein aggregate, And Retina, Hox10, Family Life Cycle, average, strong, Ocular Coloboma, human disease, Sey, Kinship Network, Genomes, MCOPCB5, eyes, MCOPCB3, visual system, hypoplasia, Hxl3, procedures, coloboma of the eye, pax6, Preimplantation Embryo Development, genetic, Methodological Studies, Komplexauge, Coloboma, Conserved, SMMCI, sample, Sonic hedgehog protein 19 kDa product, Homo sapiens disease, Mental Disorders, Uveoretinal Coloboma, Family Life Cycles, Uveoretinal, Diagnose, infrequent, close to, eye globe, screening, Ocular, embryonal development, Child Mental Disorder, Child Mental, anatomical protrusion, wide/broad, functional failure, completeness, Sonic hedgehog protein C-product, frequency, familial, SHH, vertebrate eye, Procedure, results, Diagnoses, Eyes, Incidence Rates, Postmortem, Screenings, Examinations and Diagnoses, Diseases, Obesity [Ambiguous], Obese (finding), OBESITY, Genetic Materials, embryo Ce, Neurodevelopmental Disorders Usually Diagnosed in Infancy, failure, Postmortem Diagnosis, zusammengesetztes Auge, Person-time Rate, Filiation, Genetic Material, eyeball, Diagnoses and Examination, bHLHa6, Postmortem Diagnoses, Child Mental Disorders, pax-6, coloboma of macula, ngn1, Orbital part of face, D11S812E, Heterogeneity, Exomes, signs, Adiposity, common, whole genome, Methodological, surveillance, Methodological Study, morbidity, Phenotypes, Life Cycles, disease, Neurodevelopmental, wide, Pax-6, orbital part of face, Material, spine, Festa, Colobomas, Sonic hedgehog protein N-product, Neurod3, Cistron, medical condition., inherited genetic, neurodevelopmental disorder, ocular coloboma, Secondary Attack Rates, Postimplantation, Embryonic Programmings, 9530036O11Rik, Mental Disorder, 1500038E17Rik, wagr, other disease, whole exome, xshh, compound eye, Family Member, Procedures, regio orbitalis, FESTA-L, FESTA-S, Neurodevelopmental Disorder, low frequency, number, obesity disease, adult compound eye, embryogenesis, Gene, Network, broad, disfunctional, Development, protein-containing complex, presence, Child, WAGR, protrusion, Obesity, Secondary Attack Rate, Childhood or Adolescence, Prenidation Embryo Development, Rate, Conserved Sequences, camera-type eye plus associated structures, resilient, reduced, tough, Genetic heterogeneity, Embryonic Developments, Gene Products, Studies, Hx, Mass, disease or disorder, Screening, HHG-1, hedgehog, Animal, tiny, Attack Rates, Antemortem, Trait, Technique, U19, light-detecting organ, Postnidation, Orbital region, BM040, Math4C, FOCUS, Mental Disorders Diagnosed in Childhood, MCOP2, pattern, Genetic, Genetic Heterogeneities, ShhNC, occurrence, Research, distribution, Having too much body fat, prevalence, Postnidation Embryo Development, NEUROD3, Overweight and obesity, Pre-implantation, AKA, Diagnoses and Examinations, TPT, Xhh, optic, Genotypes, non-neoplastic, Study, Cumulative, embryogenesis and morphogenesis, Disorder, Person-time, Person time Rate, Gsfaey11, disorder, coloboma of eye, Incidence Proportions, aka, Kinship Networks, constitutitional genetic, Family, Neurodevelopmental Disorders, incidence, small, Live Births, Antemortem Diagnoses, findings, Family Research, pax6a, pax6b, protein complex, Traits, Attack Rate, Cumulative Incidence, Incidence, Proteins, disorders, Post implantation Embryo Development, Sonic hedgehog protein 27 kDa product, Post-implantation Embryo Development, Preimplantation, bulbus oculi, Secondary Attack, medical condition, defective, Dsh, FVH1, Ocular Colobomas, Cistrons, Examination and Diagnoses, obesity, visual apparatus, TPTPS, near to, Family Members, Sequences, Cumulative Incidences, count in organism, mgda, an2, AN2, paper-mulberry, native protein, Genogroup, Choroid, Facettenauge, Sequence, Mass Screenings, Protein, sequence, condition, MGDA, rare (European definition), techniques, HPE3, nerve II, outbreaks, obesity disorder, Postimplantation Embryo Development, Obesity (disorder), Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains, M100081, embryonic stage, Embryonic, Embryo, HLP3, underdeveloped, Obesity NOS, Embryogenesis, Heterogeneities, Understanding, TRAITS, primary structure of sequence macromolecule, endemics, sample population, Protein Gene Products, Gene Proteins, Secondary, Genogroups, or, Incidence Proportion, Hhg1, orbital region, approaches, Attack, Families, HHG1, vicinity of, cardinality, Mental Disorders Usually Diagnosed in Infancy, epidemics, RET1, Coloboma Of Iris, Dey, hereditary, Relatives, XLPAX6, methodologyfalseUK10K RARE COLOBOMAIn the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. Ocular coloboma is the most common significant developmental eye defect with an incidence of ~1 in 5,000 live births. It results from failure of optic fissure closure during embryogenesis. The position and extent of the fusion failure dictates the clinical appearance and functional effect. ~30% of coloboma cases are associated with other systemic malformations. These UK10K samples will mostly comprise isolated coloboma cases without systemic involvement (aka non-syndromal coloboma). There is strong evidence from family studies that coloboma has a major genetic component with autosomal dominance being the most common pattern of inheritance. However, many cases are isolated or show complex patterns of familial clustering. The genes responsible for isolated coloboma are largely unknown, but in a small number of families mutations in SHH, CHX10, and PAX6 have been identified indicating marked genetic heterogeneity. Thus in addition to the clinical benefits of achieving a molecular diagnosis there are also major scientific advantages to identifying coloboma genes, as these are likely to provide insights into the complex process of optic fissure closure, that is critical to normal eye development. In the longer term, understanding the molecular basis of the disease may provide clues to therapeutic strategies.For further information with regard to this cohort please contact David Fitzpatrick (david.fitzpatrick@ed.ac.uk).2021-04-23 20:10:07EGAS000010001279606EGAD00001000179EGAD00001000307EGAD00001000415EGAD00001000206EGAD00001000185EGAC00001000205