Mutation Database Initiative
By: Aaron Hall
Over the last 5 years, the Human Genome Project has had an
enormous impact on the scientific community, which is witnessing an
explosive increase in the description of genes and disease-causing
mutations. As a result of this overwhelming expansion of data, many
problems have arisen in describing and cataloguing sequence
alterations and making them accessible to researchers. Journals
cannot publish all the mutation reports, and central databases such
as Online Mendelian Inheritance in Man (OMIM) have found it
necessary to limit the data they attempt to capture. Mutation
information currently is fragmented and incomplete, and, for most
genes, no database exists at all.
A few locus-specific databases (such as those for Factor IX, cystic
fibrosis, PAH, and BRCA1) have developed from the need of
individuals or consortiums to keep track of data for their
research. However, the usefulness of these smaller databases is
limited by their lack of uniformity in design, content, and
nomenclature making access, communication, and analysis
difficult.
This scarcity of up-to-date gene-mutation listings hampers
researchers and clinicians in determining whether a particular
mutation has been described or not. Also, investigators lack
comprehensive information on the loss of function of different
mutations in specific genes, and clinicians are unable to draw on
experiences of others who have patients with similar mutations.
Mutation Lists Vital
Complete and current mutation lists are vital for studying
genotype-phenotype relationships, treating patients with similar
phenotypes, and analyzing amino-acid residues important in the
function of gene products. Mutation lists also are needed to verify
the existence of modifier genes and assist in their identification,
monitor mutagenic environmental influences in somatic oncogenes and
tumor-suppressor genes, design diagnostic protocols, assist in
manuscript review, and examine the spectrum and type of gene
mutations. Although rare, disease-associated mutations are powerful
probes of genetic variations in populations. Knowledge of these
mutations allows researchers to provide information and services to
those affected and to characterize mutation effects in
populations.
Because researchers believe mutations in the human genome are
likely to number in the millions, a systematic approach to
collecting and maintaining mutation data is needed. Some progress
toward that goal has been achieved: Some researchers have made
their databases available via the Internet (e.g., phenylketonuria,
cystic fibrosis, mutations in factor IX, and P53), and central
databases such as OMIM have compiled partial listings of mutations
identified in specific genes. The Human Gene Mutation Database of
David Cooper and Michael Krawczak (Institute of Medical Genetics,
Cardiff, Wales) contains mutations and an index of where they are
published (http://archive.uwcm.ac.uk/uwcm/mg/hgmd0.html).
Database Association
To make comprehensive mutation lists available for research,
investigators are now forming an association of curator-driven,
locus-specific databases whose standardized content can be
downloaded onto central databases. Many believe these databases can
serve the community better because they usually are set up and
maintained by researchers, contain numerous unpublished mutations,
have a greater likelihood of being complete, and avoid the
limitations of central databases. Their bulletin-board components
contain useful information on primers, methods, and scanning
laboratories. A directory of locus-specific databases will be added
to the Web site. Another directory comprises listings in OMIM.
Project History
At an October 1994 meeting in Montreal, called to consider
nomenclature, further discussion led to an agreement to work toward
placing up-to-date mutation lists on the Internet. Attendees felt
that the curator-driven system should be simple and contain both
published and unpublished mutations. This approach was supported by
Victor McKusick (OMIM), Charles Scriver (McGill University,
Montreal), Haig Kazazian (University of Pennsylvania), Lap-Chee
Tsui (Hospital for Sick Children, Toronto), Aravinda Chakravarti
(Case Western Reserve University), and Douglas Wallace (Emory
University) as well as the American Society of Human Genetics
(ASHG), Human Genome Organisation (HUGO), and March of Dimes
(MOD).
A formal meeting in Minneapolis in October 1995, supported by MOD
and organized by HUGO, included systems experts and representatives
from prominent mutation databases, genetic and cancer societies and
journals, publishers, and central databases. Attendees endorsed the
idea of an alliance of locus-specific database curators who would
keep their own databases current and assist in implementing a
unified and uniform approach. Working groups were established on
Software and Content (Chair, Scriver), Central Database [Chairs,
McKusick and Jim Ostell (NCBI)], Nomenclature [Chair, Stylianos
Antonarakis (University of Geneva)], and Mutation Database
Association (Chair, Richard Cotton).
At a satellite meeting of HGM '96, Michael Ashburner (University of
Cambridge) outlined a proposal for a new central mutation database
that would supplement individual mutation databases. The central
database would contain core information rather than locus-specific
data and allow faster analysis of stored data. In preparation for a
half-day meeting to be held October 29 in conjunction with the ASHG
meeting in San Francisco, HGM '96 attendees agreed to place the
working groups' discussion documents on the Web site and to
initiate a mutation electronic mailing list. The mutation-database
project is now a HUGO initiative and - collaboration among Scriver,
McKusick, and Cotton. (Chair).
Article Source: http://www.articledashboard.com