human gene mutation database

1. Sri Venkateswara Institute of
Medical Sciences
The Human Gene Mutation
Database

2. The Human Gene Mutation Database (HGMD®) constitutes a
comprehensive collection of published germline mutations in
nuclear genes that are thought to underlie, or are closely
associated with human inherited disease.
INTRODUCTION
 Easily verify whether an observed mutation has been previously
described to be responsible for causing human inherited disease
Obtain an overview of the pathogenic mutational spectrum of a
particular gene or disease
Quickly access detailed reports for disease-associated human inherited
mutation

3. The first Public version of HGMD containing~10,000
variants in around 600 genes was made freely available
from Cardif via http://www.hgmd.org in April 1996.
 It is maintained in Cardiff by D.N. Cooper, E.V. Ball,
P.D. Stenson , A.D. Phillips, K. Evans, S. Heywood, M.J.
Hayden, M.M. Chapman, M.E Mort, L. Azevedo and
D.S. Millar

4. HGMD has been supported over the years by commercial
partnerships with various industry leading biomedical
research companies.
Through a partnership with Celera Genomics from 2000 to
2005, HGMD data were made available as part of the
Celera Discovery System.
 The years 2006–2015 saw the creation and continued
development of HGMD Professional, a stand-alone web
application, made available under license from BIOBASE
GmbH.

5.  In 2015, QIAGEN Bioinformatics acquired
BIOBASE, and our commercial partnership continued
with HGMD data being made available via HGMD
Professional (including data download) plus
integration into Ingenuity Variant Analysis and
Qiagen Clinical Insight.
The latest version of HGMD (2020.2) contains 289,346
different mutations in 11,076 genes

6. These additions are limited to "association",
"association with" and "increased" or "lower" "risk",
depending on how the polymorphism was reported.
Question marks are sometimes included to indicate that
the association is a tenuous one. Some of the
polymorphisms are included as "variants" only.
 This will occur for any polymorphism reported as
possibly clinically significant, but without an associated
clinical phenotype.

7. in March 1999, HGMD began to include disease-associated
polymorphisms.
 These are extracted from the same journals that are scanned
for mutations (>250). To be included, there must be a
convincing association of the polymorphism with the
phenotype.
These polymorphisms are currently identified in the database
by an addition to the phenotypic description.

8. Data are collected weekly by a combination of manual and computerised
search procedures.
 In excess of 250 journals are scanned for articles describing germline
mutations causing human genetic disease.
The required data are extracted from the original articles and augmented with
the necessary supporting data.
Data included are mainly from the original published reports, although some
data have been taken from 'Mutation Updates' and review articles.
 Unpublished mutations and mutations reported only in abstract form are not
included. Reports of such lesions can be however accessed for some genes via
the Locus-Specific Mutation Databases.
Data collection

9. The HGMD web interface is designed to be as easy to use as
possible.
 Each gene has been assigned its own "home page", where all other
links are located. Each home page contains a table detailing the
type and number of mutations logged in HGMD, with hypertext
links to the mutation pages.
The second table contains details on entries in HGMD categorized
by phenotype, with links to Online Mendelian Inheritance in Man
(OMIM) entries matching these phenotypes.
Web-Page Layout
Contud…...

10. Meaningful integration of the data with
phenotypic, structural and mapping information
on human genes has been accomplished
through bi-directional links
between HGMD and both the Genome Data
Base (GDB) and Online Mendelian Inheritance
in Man (OMIM), Balitmore, USA.
 These links can be found at the bottom of each
page.. Contud…...

11.  We have recently also added links to the Nomenclature
Database, Genatlas and Geneclinics, where corresponding
pages are available.
 In addition, hypertext links have been established
from HGMD references to Medline abstracts through Entrez,
on each mutation page. Links are also available to other
facilities provided by HGMD, such as mutation maps and
cDNA sequence information

12.  These sequences consist of approximately 25 bp of exonic sequence,
(uppercase) along with up to 25 bp of intronic sequence, (lowercase).
 The amount of intronic sequence will vary due to the currently
limited availability of such sequences in the literature and Gen Bank.
 The initiating methionine and termination signals are marked in each
sequence by square brackets [ATG], [TAA]. Square brackets are also
used to define split codons where they occur at the splice junction.
 Normal brackets ( ) are used when a series of identical bases is
encountered in the intronic sequence. Hence, t(6) would indicate a run
of 6 t's at that position.

14. Enter search term:
There are five ways HGMD may be searched.
1. Gene symbol search - searches HGMD for the official HUGO
Gene Nomenclature Committee gene symbol.
2. Gene description search - searches HGMD for the full gene description, again as
recorded by the Nomenclature Committee. Older gene symbols (if present) can also
be searched for here. 3. OMIM number search - OMIM gives each gene entry in
its database a unique number, which can also be used to search HGMD.
4. GDB number search - GDB gives each gene entry in its database a unique
number, which can also be used to search HGMD.
5. Disease/phenotype search - Searches HGMD for the disease/phenotype
associated with reported mutations in HGMD genes.
Results will contain a list of genes associated with your search terms. To access the
HGMD record for that gene, click on the gene symbol.
Primary search
Gene symbol
Submit

15.  Wildcards (*) are permitted when conducting gene
symbol, gene
description or disease/phenotype searches. Also,
alternate spelling support has recently been added.
 For example "haemophilia" and "hemophilia" should
now both lead to the F8 and F9 genes. The alternate
spelling function will only work with complete words.
 If you find any alternate spellings for words which are
not supported, please report them to us using
our comment form.

16. Symbol:
The secondary search allows users to jump to a
specific mutation data set if the exact gene symbol is
known. This search will only function with the correct
HUGO Nomenclature Committee gene symbol. Please
note that users must now register for access to HGMD
mutation data.
Secondary search
Missense/nonsense Go!

18. Locus-Specific Mutation Databases
A considerable number of locus-specific mutation
databases have been constructed and made publically
available via the internet. Many of the lesions present in
these databases are included in the Human Gene
Mutation Database. However, the locus-specific
databases may contain additional unpublished material.
An article reviewing current locus-specific databases
recently appeared in Genome Res (2002) 12: 680-688.

20. HGMD® Login

21. HGMD User Registration

22. HGMD has been publicly available via the internet since
April 1996. During this time, the database has grown
considerably (from under 10,000 mutation entries in 1996 to
over 76,000 entries by January 2008). An enormous effort is
required to maintain a fully curated database of this size and
to provide effective search and analysis software tools to
query the data. It is therefore vitally important to identify
sustainable long-term funding for HGMD, so that we may
continue to be able to provide this service to the scientific
community for years to come.

24. HGMD is currently in the process of expansion and up-dating
designed to make it a quick, easy, accessible and authoritative
reference source to all inherited gene lesions in human. The availability
of such a resource will allow
the rapid assessment of current diagnostic possibilities both for the
molecular genetic analysis of a particular disease and for the direct
detection of specific mutations at a given locus.
determination of the nature and distribution of mutations within a
given gene so as to optimize mutation screening procedures.
Contud…...

25.  In conclusion, HGMD contains an expansive set of
tools that may be utilised by users in the fields of
clinical diagnostics, personalised genomics and
NGS/bioinformatics research to search and prioritise
results derived from its comprehensive mutation data
set.
 The onus is, however, on the clinician or researcher to
use these tools and data sensibly and appropriately to
obtain results that are suitable for their own use cases.