Genetic Eye Disease Related Terms and Resources

From EyeWiki


The ophthalmologist’s role in the management and diagnosis of genetic disorders can be critical for patients, families and referring providers in the steadily advancing field of genetics. Genetic testing can be a useful medical tool in ophthalmology to help confirm or rule out a suspected inherited ocular disorder, provide important information of inheritance patterns and risk of recurrences for families, and help guide clinical management, appropriate referral and surveillance decisions. Furthermore, genetic testing may also provide a societal benefit in improving the understanding of genes, genetic diseases, and future treatments.

Testing offered may be clinical or research-based, and may be carried out in the prenatal period, as part of the newborn screening, used to determine carrier status, or can be used for diagnostic purposes. Common genetic tests used to confirm or make a diagnosis include, but are not limited to, chromosomal karyotype or microarray, fluorescence in situ hybridization (FISH) and sequencing. (See Section 2 and Section3/Table 1)[1] [2] [3] [4] Advances in our knowledge of both genetic disease and diagnostic technological capabilities continues to exponentially improve, however, there are still many limitations in each of the available genetic diagnostic testing modalities. In addition, the ethical concerns and psychosocial impact of the genetic test results can be substantial for the patient being tested, the family members, and for the clinician and medical team involved.[5] Financial burdens also exist, as costs can range from hundreds to thousands of dollars for a single test. Many insurance carriers now have guidelines in place to determine medical necessity that generally include examining the clinical validity of the genetic test being requested, the clinical signs and symptoms present, the risk involved for the disease of concern based on family history, and how the result from the test will ultimately affect the medical management.[6]

Tests results may return as positive indicating a change in the area of interest, negative indicating there was no change found, or as a variant of uncertain significance (VUS) indicating a change has been found but that the significance of this change is not well understood. Therefore both the decision to undergo testing and the interpretation of the results are complex entities and should involve trained individuals with an expertise in this area and knowledge of genetic counseling. Genetic testing is generally performed by a geneticist or a genetic counselor, or ordered in consultation with them.

Recommendations for genetic testing include 1) to test for a disorder for which the causative genes have been identified, 2) use a Clinical Laboratories Improvement Amendments (CLIA) approved laboratory, 3) order the most specific test and avoid unnecessary parallel testing, 4) avoid testing for genetically complex disorders for which no treatment or surveillance guidelines exist, and 5) avoid genetic testing in asymptomatic minors when involving untreatable disorders except in rare circumstances.[7] Several genetic terms and resources are listed as follows to assist in managing the numerous and steadily growing list of ocular inherited diseases. (See Section 2 and 4)[1][2][3][4][8]

Definitions of Common Genetic Terms

Adeno-associated virus (AAV) vectors Vectors derived from adeno-associated viruses, and the most frequently used delivery systems in ocular gene therapy.
Alleles A variant of a gene located at a certain locus.
Amino acid sequence Refers to the order of amino acids in a polypeptide chain.
Amino acids A class of biological molecules characterized by an amine and carboxylic group along with a particular functional group. They are the main building blocks of proteins and have other important biological functions.
Aneuploidy The state in which one or more extra or missing chromosomes is detected.
Anomaly An anatomical departure from the phenotype present in the reference population.
Association Unrelated pattern of anomalies in occurrence more often than expected by chance.
Autosome A chromosome that is numbered and not considered a sex chromosome.
Autosomal dominant inheritance An inheritance pattern in which only one copy of a particular autosomal chromosome is needed in order to produce the effects that the inherited chromosome presents with.
Autosomal recessive inheritance An inheritance pattern in which two copies of a particular autosomal chromosome is needed in order to produce the effects of those particular inherited chromosomes.
Carrier testing A form of genetic testing used on individuals that may not present with any genetic disorder but are at risk of passing down the a trait due to being a carrier. This usually relates to being a carrier of an abnormal autosomal recessive or X-linked disorder.
Central dogma of Molecular Biology Describes the flow of genetic material in that DNA encodes for RNA (transcription), which in turn then encodes for proteins (translation). Exceptions to the classic dogma are now known to exist.
Chromosomal Karyotype A photographic representation of an individual cell's chromosomes that is used to analyze the number and structure of the chromosomes.
Chromosomal Microarray Evaluates the genome in a high resolution by utilizing arrayed small DNA pieces to provide a locus by locus measurement of DNA copy number variation at numerous loci simultaneously.
Chromosome An organized and packed structure of DNA, RNA, and proteins located within a cell.
Chromosome Translocation An abnormality that involves the exchange of genetic material of non-homologous chromosomes. Translocations can involve the exchange of equal amounts of material (balanced) or involved additional or missing material (unbalanced).
Clinical genetic testing Genetic testing performed to discover information for the patient and family involved.
Clinical Laboratory Improvement Amendments (CLIA) Laboratory testing U.S. federal regulatory standards that was first established in 1988 that requires certification for any lab prior to performing clinical diagnostic testing on human samples. The Center for Disease Control (CDC), Center for Medicaid Services (CMS), and the Food and Drug Administration (FDA) play a role in the function of CLIA.
Cloning A process that consists of creating identical copies of DNA, a cell, or an organism.
Consanguinity Used to describe genetic relatedness between individuals due to a common ancestor of origin.
Consultand The person in the family that presents for a genetic counseling evaluation regarding a known or potential inherited condition.
De novo (sporadic) mutation An altered gene that appears in the germline or fertilized egg that was not manifested in the family lineage, particular both of the parents.
Deletion Change in the DNA sequence involving a portion of the DNA being removed.
Deoxyribonucleic acid (DNA) A biological molecule, double stranded, that encodes the genetic information of an organism.
Direct-to-consumer genetic testing Genetic testing marketed and sold directly to consumers without the involvement of healthcare professionals.
Direct-to-consumer genetic testing through physician Genetic testing marketed directly to consumers and physicians, and requires the physician to order the test.
Disease Condition involving abnormal cognitive or physical function.
Duplication Change in the DNA sequence involving an extra copy or copies of a portion of the DNA.
Exome The part of the genome that corresponds to the complete set of exons.
Exons Sequences in the DNA that corresponds to protein coding regions.
Fluorescence in situ hybridization (FISH) Uses a targeted approach to analyze a specific sequence of a chromosome. The technique consists of using a specific probe DNA that is labeled and is hybridized to a sample DNA of interest. Recording of the labeled hybridization, or lack of, can then be analyzed.
Frameshift mutation Change in the DNA sequence, either an insertion or deletion, not a multiple of three, which causes a shift in the reading frame.
Genes A sequence of DNA that corresponds to a unit of hereditary information, usually coding for a protein.
Gene therapy The experimental process of inserting genes for the purpose of treatment.
Genetic counselor A health professional specialized in the area of genetics and counseling about various genetic information to individuals.
Genetic Information Nondiscrimination Act (GINA) Legislation passed by the US Congress that prohibits employers and health insurance agencies from using genetic information in decisions.
Geneticist An individual specialized in the study of genetics, which is composed of genes, heredity, and variation.
Genome browser An online site that contain a collection of genomic data information.
Genome-wide association study (GWAS) A technique that is used to study genetic markers across complete sets of DNA in different people in order to find genetic variation in a particular trait.
Genotype The genetic makeup of an individual usually referring to a specific set of alleles or traits.
Germinal mutation A change in the DNA sequence in the germline, and therefore can be passed on to the next generation.
Germline The cell line in which the gametes are formed from.
Hemizygosity State when only one copy of a gene is present in a diploid cell.
Human genome project An international research study that sequenced the entire human genome and determined the genes that are encoded.
Incomplete penetrance Refers to the presence of a gene change that is not phenotypically expressed in some individuals, but is expressed in others.
Insertion Change in the DNA sequence involving an additional amount of DNA added in a new location.
Introns Non-coding sequence found in DNA that is usually excised before translation.
Loss of heterozygosity (LOH) Presence of only one copy of an allele such as due to a loss of a portion of a chromosome within a tumor tissue.
Malformation A non-progressive congenital anomaly.
Massively parallel sequencing High-throughput DNA sequencing that allows for numerous strands of DNA to be sequenced in a parallel fashion. Also called next-generation sequencing.
Meiosis A form of cell division consisting of two nuclear division of a diploid resulting in the formation of haploid gametes.
Mendelian genetics Genetics inheritance pattern proposed by Gregor Mendel that is composed of three main laws. The Law of Segregation states that allele segregation results in one allele per gamete. The Law of Independent Assortment states genes from different traits segregate independently. Law of Dominance states that alleles may be dominant or recessive and dominant alleles overshadow recessive alleles.
Missense mutation Change in the DNA sequence involving a single base pair which causes an amino acid being substituted for another.
Mitochondrial inheritance A form of inheritance from the genetic material located within the mitochondria. This form of inheritance is maternal and is always inherited due to being part of the ovum.
Mitosis A form of cell division in which somatic cells produce identical daughter cells.
Mosaicism The presence of two or more cell populations that differ in their chromosomal genotype.
Multifactorial inheritance A combination of various genetic and environmental factors that contribute to the development of a trait.
Mutation A change in the DNA sequence of a gene.
Newborn screening Testing performed on newborn babies to detect for a wide variety of disorders.
Nonsense mutation Change in the DNA sequence involving a single base pair that results in a premature stop codon, which leads to a shortened protein.
Nucleic acid sequence Refers to the arrangement of letters that make up the nucleotide order in RNA and DNA.
Nucleotide A nitrogenous base attached to a phosphate group and a pentose sugar molecule. A ribonucleotide, main unit of RNA, is composed of a phosphate group, a ribose sugar, and a nitrogenous base (Adenine(A), Cytosine (C), Guanine (G), or Uracil (U)). A deoxyribonucleotide, main unit in DNA, is composed of a phosphate group, deoxyribose sugar, and a nitrogenous base (Adenine (A), Cytosine (C), Guanine (G), or Thymine (T)).
Obligate carrier Individual that must be a carrier of the genetic mutation of concern based on the known disorder inheritance pattern and family history obtained.
Ovum A mature female haploid gamete.
Panel tests Used in order to assess for mutations in multiple genes.
Pedigree A genetic representation of a family lineage that demonstrates various inheritance patterns in the family tree.
Personalized medicine A form of medical practice that uses an individual’s genetic makeup to guide treatment.
Pharmacogenetics A branch of pharmacology that studies the genetics responses to drug treatments.
Phenotype The observable physical representation of an expressed gene.
Polymerase chain reaction (PCR) Technique that allows a short sequence of DNA or RNA to be amplified.
Proband An individual that is being studied on in genetics studies. Usually refers to the first affected family member with a genetic disorder or trait that begins the study of the family.
Proteins A class of biological molecules that are composed of chains of amino acids.
Reflex testing Automatic subsequent testing that takes place after an initial testing result.
Repeat expansion Change in the DNA sequence involving consecutive repeated portions of short amounts of DNA.
Research genetic testing Genetic testing performed as part of a research study to advance our knowledge of understanding genetic diseases, genes, and testing methods which may or may not provide immediate beneficial information to the patient or family involved.
Ribonucleic acid (RNA) Biological macromolecule, single stranded, which primarily conveys information from DNA to control protein synthesis.
Sanger (dideoxy) sequencing A technique for DNA sequence analysis that utilizes dideoxy nucleotides that will terminate the growing chain.
Sequencing The process of determining the sequence of a part of the genome.
Silent mutation Change in the DNA sequence that does not actually change the protein sequence.
Single gene tests Analyzes a single gene in a sample DNA of interest in order to determine any abnormalities or absence of that single gene.
Single nucleotide polymorphism (SNP) A form of DNA sequence variation in which a single nucleotide differs in a particular genome location in two or more members of a population.
Somatic Any cell of the body excluding the gametes.
Somatic mutation A change in the DNA that occurs after the conception period, therefore not passed on to the next generation.
Sperm A male reproductive cell used in fertilization.
Splice site mutation Change in the DNA sequence involves the location where intron splicing occurs.
Substitution Change in the DNA sequence that replaces one base for another base.
Syndrome Causally related pattern of anomalies.
Uniparental disomy A genetic inheritance situation in which both members of a chromosomal pair or both segments of chromosome are inherited from one parent and neither is inherited from the other parent.
Variant of uncertain significance (VUS) A variation in a gene sequence in which the association of the variation with any disease is unknown.
Whole Exome Sequencing A technique used to analyze the entire coding sequence, exons, of a DNA sample of interest. The DNA sample is compared to a control sample by detecting any changes in nucleotide sequences.
Whole Genome Sequencing A technique that determines the entire DNA sequence in a genome.
X-linked dominant inheritance A form of inheritance in which a dominant gene is carried on an X chromosome and is expressed with only one copy necessary.
X-linked recessive inheritance A form of inheritance in which a recessive gene is carried on an X chromosome. Only requires one copy to be expressed in a male and two copies to be expressed in a female.
Zygote A diploid cell formed from the fusion of a sperm cell and an ovum.

Table1. Comparison of Selected Genetic Tests

Genetic Test Comparison.jpg

Genetic Resources

American Academy of Ophthalmology (AAO) Recommendations for Genetic Testing of Inherited Eye Diseases AAO task force's 2014 recommendations for ophthalmic genetic testing.
American Board of Genetic Counseling The organization in charge of giving credential certification in the field of genetic counseling in the United States and Canada.
American College of Medical Genetics An organization composed of various individuals with specializations in genetics focused on the practice of medical genetics.
American Society of Human Genetics Professional organization for specialist in human genetics.
Atlas of Genetics and Cytogenetics in Oncology and Haematology Online encyclopedia and database atlas of genes, cytogenetics and cancer diseases that includes an overview of eye tumors
Children's Craniofacial Association Educational resource and patient support for craniofacial syndromes A database that contains clinical studies of human participants from around the world.
FACE2GENE by FDNA A search and reference application that utilizes Facial Dysmorphology Novel Analysis (FDNA®) technology to detect dysmorphic features from facial photos
GeneCards Comprehensive database containing information on known and predicted human genes.
GeneReviews Publications consisting of standardized and clinical information for the diagnoses, management, and treatment of patients with inherited conditions.
Gene Tests Information about clinical and research testing for genes.
Genetic Alliance Nonprofit health advocacy group with a network of over 1,200 disease advocacy organizations that has a focus of promoting health in genetic research and technology.
Genetic and Rare Disease Information Center (GARD) A database that is part of the NIH that provides useful information about genetic and rare diseases.
Genetics Home Reference A website that provides information about genetic variations.
Geneva Foundation for Medical Education and Research (GFMER) Atlas of Developmental and Genetic Diseases Atlas of developmental and genetic eye diseases.
Hereditary Ocular Disease, University of Arizona A database of hereditary ocular diseases for patients and clinicians.
HUGO Gene Nomenclature Committee (HGNC) Authority that assigns the nomenclature standards for human genes.
Human Genome Variation Society (HGVS) Maintains genomic variation data and nomenclature information on sequence variants.
Human Phenotype Ontology Ontology of human phenotypic abnormalities.
International Society for Genetic Eye Diseases & Retinoblastoma (ISGEDR) Professional organization with a goal of promoting shared information, collaborations and the dissemination of scientific knowledge of genetic diseases of the eye and in retinoblastoma.
London Ophthalmic Genetics Database (GENEEYE) Comprehensive database and image library of genetic ophthalmic conditions.
MedGen Published material related to human medical genetics.
My Family Health Portrait Tool used to create a family health history.
National Center for Biotechnology Information (NCBI) Formed as a division of the National Library of Medicine in 1988, which now serves as a central hub for providing numerous databases, tools and educational resources of biomedical information.
National Center for Education in Maternal and Child Health's MCH Library Online database that provides information and resources for maternal and child health.
National Human Genome Research Institute Glossary Contains terms and concepts used in the study of genetics for the public.
National Institutes of Health Genetic Testing Registry (GTR) Serves as a centralized location for providers to submit genetic test information.
National Newborn Screening & Global Resource Center (NNSGRC) Contains information on newborn screening, state contacts, general resources, and provides information sheets that describes the proper steps to follow after receiving a screening report
National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE) National Eye Institute research initiative allowing researchers access to DNA samples, clinical data, and patients interested in research.
National Organization for Rare Disorders (NORD) An organization that provides support to those with rare disease by providing funding, research, education, and networking.
National Society of Genetic Counselors An organization composed of trained genetic counselors and other health professionals dedicated to the promotion of genetic counseling.
OMIM(Online Mendelian Inheritance in Man) A database of human genes and genetic phenotypes.
Orphanet Provides information about rare diseases and treatments.
Pedigree Nomenclature A standard used in the design of pedigrees to provide consistent information to research and health professionals as well as those in training. (Bennett RL et al, Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors, J Genet Couns. 2008 Oct;17(5):424-33, doi: 10.1007/s10897-008-9169-9. Epub 2008 Sep 16)
PubMed US National Library of Medicine (NLM) service that provides a search engine database of biomedical and life sciences literature citations; developed by the National Center for Biotechnology Information (NCBI).
Unique Provides resources and support for families of children that have rare chromosome disorders


  1. 1.0 1.1 Genetics Home Reference Glossary, World Wide Web URL:
  2. 2.0 2.1 Hartwell, L. (2004). Genetics: From genes to genomes (2nd ed.). Boston, Mass.: McGraw-Hill Higher Education.
  3. 3.0 3.1 Mayo Clinic Health Information, World Wide Web URL:
  4. 4.0 4.1 National Human Genome Research Institute, World Wide Web URL:
  5. Karthikeyan A. Sadagopan, Jenina Capasso, and Alex V. Levin, Genetics for the ophthalmologist, Oman J Ophthalmol. 2012 Sep-Dec; 5(3): 144–149, doi: 10.4103/0974-620X.106092, PMCID: PMC3574508
  6. Jenina E. Capasso, The Cost of Genetic Testing for Ocular Disease, Curr Opin Ophthalmol. 2014;25(5):394-399
  7. Edwin M. Stone, MD, Ph.D., Anthony J. Aldave, MD, Arlene V. Drack, MD et al., Recommendations for Genetic Testing of Inherited Eye Diseases, 2012 American Academy of Ophthalmology
  8. Hennekam RC, Biesecker LG, Allanson JE, et al., Elements of Morphology Consortium. 2013. Elements of morphology: General terms for congenital anomalies. Am J Med Genet Part A 161A:2726–2733.