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Exploring Online Genetics Sources

Learning Outcomes

Upon completing this practical the student will be able to

• easily search for, find, and utilize online genetics sources;
• easily navigate through the National Center for Biotechnology Information (NCBI)'s web page;
• start answering biological questions through online sources.

Background

Internet has become a fundamental tool in human genetics and genomics education and research. It provides access to numerous online sources that facilitate data storage, access, and analysis by end users including scientists, students, clinicians, patients, and public readers [1].

Development of online sources for human genetics and genomics began in the 1980s. Since then, online sources providing information and data on genetics and genomics research have been rapidly growing. Internet has become the most popular source for accommodating the most up-to-date research outcomes and innovations in the field [2].

A broad range of genetic and genomic data is available online for access and analysis. Examples include online databases for gene mapping, mapping of chromosomal regions, epigenome mapping, sequence data on DNA, RNA, and protein, species-specific sequence data and comparisons among species, disease-specific data, gene expression data from normal and diseased tissues, genome browsers, and literature information. Utilization of these sources could be tailored to address specific research questions by end users.

One of the most important advances in genetics has been the generation of whole genome sequence data. The availability of whole genome sequences offers a vast array of genetic data on coding regions, noncoding regions, chromosomal structure and gene organization, genes, gene locations on chromosomes, number of genes, number of base pairs, nucleotide sequences, and DNA variants. [3] So far, diverse organisms including species from bacteria, eukarya, and archaea domains have been sequenced. Some of the earlier examples are Haemophilus influenzae (1995), Saccharomyces cerevisiae (1996), and Caenorhabditis elegans (1998) [4-6].

For the purposes of this book, only the human genome project will be detailed.

Human Genome Project

Human genome project, launched in 1990, is an internationally renowned research project. It was constructed to define the genetic, physical, and sequence maps of the human genome by deciphering the entire nucleotide sequence. Revelation of the entire genomic sequence enabled identification of genes dispersed throughout the genome [7, 8].

Access to the complete genome sequence has revealed information on genes, regulatory elements, and chromosomal organization and structure and this has facilitated the start of a new era in the field of human genetics [8].

In the recent years, advancement of next generation sequencing technologies has enabled time-efficient and cost-effective sequencing of whole genomes. These high-throughput sequencing technologies define a milestone in human genetics and genomics research. Such technologies enable investigating genome integrity and genetic variations across the human genome and hold great promise for easing the diagnosis of Mendelian conditions as well as multifactorial disorders. Moreover, these technologies aid in translation of human genetic variants into clinics by targeting prediction, prevention, and variant-specific drug discovery [8].

Rapid accumulation of large volumes of sequencing data has made manual functional analysis impossible. Hence, computational tools and databases have been employed for data analysis of high-throughput sequencing. It should be noted that in most cases computational sequence analysis should be supplemented with further functional studies in the investigation of inherited human traits and disorders [8].

As an outcome of high-throughput sequence analysis large amounts of genomic and epigenomic data have become available in databases such as the National Center for Biotechnology (NCBI), University of California Santa Cruz (UCSC) Genome Browser, the encyclopedia of DNA elements (ENCODE), and the roadmap epigenomics project. These databases are detailed below.

National Center for Biotechnology Information (NCBI)

NCBI is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health, legally established in 1988. Its initial aim was to develop computer-based systems for collection, interpretation, and presentation of accumulating data in human molecular biology, genetics, and biochemistry. It has since evolved to act as an international platform for data sharing and computer-based data analysis, comprehensively covering information from all organisms [9].

NCBI's homepage contains a wide range of biological information that can be accessed and downloaded. NCBI's Entrez interface provides the links for a vast array of databases, including Gene, a database with a specific focus on gene-specific data providing information on gene locus, gene product, nucleic acid sequence, annotated sequence variants, gene maps, and gene homologs with additional links to external databases. NCBI provides access to OMIM(online Mendelian inheritance in man) a well-established database providing information on heritable disorders and the disease-causing genes, their chromosomal locations and maps, phenotype-genotype relationships, and clinical features (molecular genetics and cytogenetic aspects are also involved). Another fundamental constituent of NCBI is the PubMed database, which provides access to the online archive of biomedical literature abstracts and articles through MEDLINE and scientific journals. The organization of NCBI allows interconnection among these various databases.

Several other databases are embedded within the NCBI, which are listed in NCBI's homepage and use of these databases is demonstrated through NCBI's training and tutorials. Table 1.1 lists some of these databases.

UCSC Genome Browser

Upon completion of the first working draft of the human genome project in 2000s, the assembled genome has been accessible at the UCSC genome browser [10]. Today, the genome browser broadly serves to visualize and analyze genome assembly data that is gathered from UCSC or from other sources (user-supplied data). UCSC harbors the genome assembly of more than 93 organisms including humans, chimpanzees, mice, and zebra fish [10]. UCSC Genome Browser enables access to the following data: mapping and sequencing (i.e. base positions, GC contents, contigs, and scaffolds), genes and gene predictions (i.e. consensus CDS, noncoding RNA), phenotype and literature, mRNA and ESTs, expression, regulation (i.e. integrated regulation from ENCODE, CpG islands), comparative genomics, variation (i.e. single nucleotide polymorphisms [SNPs]), and repeats (i.e. microsatellite) [10, 11].

In addition, there are also various analysis tools available in the UCSC Genome Browser including the genome browser, which enables visualization of genomic data; BLAT, which is used for sequence alignment; in-silico PCR, which aligns primer sequences to genomes; and Gene Sorter, which enables search for similar genes by expression metrics.

The Encyclopedia of DNA Elements (ENCODE)

ENCODE, a collaborative project of different nations funded by the National Human Genome Institute, serves as a follow-up of the human genome project. It aims to investigate the functional DNA sequences of the human genome. ENCODE provides information on the reference human genome including coding and noncoding regions, i.e. protein-coding genes, noncoding transcripts, long noncoding RNAs, pseudogenes; subcellular localization of transcripts in humans by RNA sequencing; DNA methylation; chromatin accessibility indicator of DNA regulatory regions; transcription factor binding sites, three-dimensional space interaction; and integration of SNPs achieved from genome-wide association studies (GWAS) [12-14].

Table 1.1 List of selected databases accessible through NCBI's homepage.