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Functional genomics is the interpretation of the function of DNA
sequence on a genomic scale. Already, the availability of the sequence
of entire organisms has demonstrated that many genes and other
functional elements of the genome are discovered only when the full
DNA sequence is known. Such discoveries will accelerate as sequence
data accumulate. However, knowing the structure of a gene or other
element is only part of the answer. The next step is to elucidate
function, which results from the interaction of genomes with their
environment. Current methods for studying DNA function on a genomic
scale include comparison and analysis of sequence patterns directly to
infer function, large-scale analysis of the messenger RNA and protein
products of genes, and various approaches to gene disruption. In the
future, a host of novel strategies will be needed for elucidating
genomic function. This will be a challenge for all of biology. The HGP
will be contributing to this area by emphasizing the development of
technology that can be used on a large scale, is efficient, and is
capable of generating complete data for the genome as a whole. To the
extent that available resources allow, expansion of current approaches
as well as innovative technology ideas should be supported in the
areas described below.
a) Develop cDNA resources. Complete sets of full-length cDNA clones
and sequences for both humans and model organisms would be enormously
useful for biologists and are urgently needed. Such resources would
help in both gene discovery and functional analysis. High priority
should be placed on developing technology for obtaining full-length
cDNAs. Complete and validated inventories of full-length cDNA clones
and corresponding sequences should be generated and made available to
the community once such technology is at hand.
b) Improved technologies are needed for global approaches to the study
of non-protein-coding sequences, including production of relevant
libraries, comparative sequencing, and computational analysis.
c) Develop technology for comprehensive analysis of gene expression.
Information about the spatial and temporal patterns of gene expression
in both humans and model organisms offers one key to understanding
gene expression. Efficient and cost-effective technology needs to be
developed to measure various parameters of gene expression reliably
and reproducibly. Complementary DNA sequences and validated sets of
clones with unique identifiers will be needed for array technologies,
large-scale in situ hybridization, and other strategies for measuring
gene expression. Improved methods for quantifying, representing,
analyzing, and archiving expression data should also be developed.
d) Improve methods for genome-wide mutagenesis. Creating mutations
that cause loss or alteration of function is another prime approach to
studying gene function. Technologies, both gene- and phenotype-based,
which can be used on a large scale in vivo or in vitro, are needed for
generating or finding such mutations in all genes. Such technologies
should be piloted in appropriate model systems, including both cell
culture and whole organisms.
e) Develop technology for global protein analysis. A full
understanding of genome function requires an understanding of protein
function on a genome-wide basis. Development of experimental and
computational methods to study global spatial and temporal patterns of
protein expression, protein-ligand interactions, and protein
modification needs to be supported.