| What is Online Mendelian Inheritance In Man (OMIM)? | • Comprehensive, authoritative and timely knowledge base of human genes and genetic disorders.
• One of the best websites for detailed and updated information of genetic diseases.
•Established in 1995 by the National Centre for Biotechnology Information (NCBI).
•About 25,000 entries, including 9,000 represented phenotypes and 16,000 represented genes |
| What are the Disorders Dealt with in OMIM? | ❖Those inherited in a Mendelian fashion, e.g., genetic skin diseases and syndromes such as the ichthyosis, epidermolysis bullosa, neurofibromatosis and lipoid proteinosis.
❖Immunological or inflammatory disorders with a polygenic inheritance such as atopic dermatitis, psoriasis etc.
❖Does not include conditions resulting from chromosomal aberrations. |
| What are OMIM Codes | Each genetic disorder has been allotted a unique six digit OMIM code. The first digit indicates the mode of inheritance of the disorder
1. (100000- ) Autosomal dominant loci or phenotypes
2. (200000- ) Autosomal recessive loci or phenotypes
3. (300000- ) X-linked loci or phenotypes
4. (400000- ) Y-linked loci or phenotypes
5. (500000- ) Mitochondrial loci or phenotypes
6. (600000- ) Autosomal loci or phenotypes |
| What are OMIM Symbols | • An asterisk (*) before an entry number indicates a gene.
• A number symbol (#) before an entry number indicates that it is a descriptive entry, usually of a phenotype, and does not represent a unique locus.
• A plus sign (+) before an entry number indicates that the entry contains the description of a gene of known sequence and a phenotype.
• A percent sign (%) before an entry number indicates that the entry describes a confirmed Mendelian phenotype or phenotypic locus for which the underlying molecular basis is not known.
• No symbol before an entry number generally indicates a description of a phenotype for which the Mendelian basis, although suspected, has not been clearly established or that the separateness of this phenotype from that in another entry is unclear.
• A caret (^) before an entry number means the entry no longer exists because it was removed from the database or moved to another entry as indicated. |
| What is ClinVar? | Freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence
➢Facilitates access to and communication about the relationships asserted between human variation and observed health status
➢A major goal is to support computational (re)evaluation, both of genotypes and assertions, and to enable the ongoing evolution and development of knowledge regarding variations and associated phenotypes |
| What is the four domains of information ClinVar integrates? | Variation, phenotype, interpretation, Evidence |
| How does ClinVar aggregate data by variant and phenotype ? | . |
| Explain ClinVar Review Statuses? | Expert panels – both medical and research experts with published criteria and process for evaluating variant pathogenicity
• CFTR2, InSiGHT
Professional society – groups that provide practice guidelines
• American College of Medical Genetics (ACMG) |
| How does ClinVar Aggregates Data by Variant? | . |
| How to access ClinVar Data? | Interactively on the web, updated weekly Monthly full releases
• Comprehensive XML extraction
• VCF files
• Tab-delimited summary files for genes, variants
E-utilities as web service or via command line Annotation on graphic sequence displays
Variation Viewer, www.ncbi.nlm.nih.gov/variation/view/ Variation Reporter,
www.ncbi.nlm.nih.gov/variation/tools/reporter |
| What is the problems with ClinGen ? | >100 million genomic variants in humans
>20,000 genes
Most we don’t understand |
| Compare ClinVar vs. ClinGen? | -ClinVar is a database
-ClinGen, The Clinical Genome Resource, is an NIH funded program supporting a wide range of activities encompassing both support for ClinVar (funded through NCBI) as well as other projects |
| What are the Goals of ClinGen? | To raise the quality of patient care by:
• Standardizing the annotation and interpretation of genomic variants
• Sharing variant and case level data through a centralized database for clinical and research use
• Developing machine-learning algorithms to improve the throughput of variant interpretation
• Implementing an evidence-based expert consensus process for curating genes and variants
• Assessing the actionability of genes and variants and supporting their use in clinical care systems |
| What is Mendelian disease variant terminology? | • Pathogenic
• Likely pathogenic ← (≥90% confidence) • Uncertain significance (VUS)
• Likely benign
• Benign
Replace terms “mutation” and “polymorphism” with “variant” |
| What is the Data flow in ClinGen? | . |
