Welcome to Genome Browser Tutorial Level 0. This is a tutorial meant to describe Genome Browser in basic, general terms, with the goal of introducing you to its central functions and available information. Hopefully this will help you decide if you will be able to use this tool to find the right information about the gene, sequence, regulatory element, or protein in which you are interested. This tutorial is best for those who have never used Genome Browser before.
What is Genome Browser?
Click this link to open Genome Browser: https://genome.ucsc.edu/
Welcome to the Genome Browser. Now…where for the love of Hubble have you ended up? Genome Browser is a fantastic tool created by the University of California Santa Cruz. This is essentially a collection of big DNA sequence maps with all the known annotations of sequence function and expression (what does what and how much), chromosome marks and structures (how is the DNA physically arranged?), and protein data (what does this bit of DNA make and how does it work?).
How is the genome assembly and reference sequence created?
A genome sequencing process produces millions of small sections of fragmented sequence. Researchers (or rather their computer programs) must then look for overlapping sections that help them order the fragments as they are in the chromosome. The compiled order they create is called the genome assembly. The generally agreed upon or ‘normal’ state is the reference sequence. For more information on forms of sequencing, look here: DNA sequencing and Sanger Sequencing.
How does it work?
The Basic Local Alignment Tool (BLAT) compares the sequence you give it to the reference sequence to pinpoint the section of the genome to which that sequence fragment belongs. This is essentially a “Control–Find” function. If you instead search for a particular known gene rather than a portion of DNA code, Genome Browser will search the genome assembly for the map of your gene and can provide you with its reference sequence– this is the “expected” sequence for your gene of interest. Be advised that you may find differences in the particular sample you work with due to mutation or normal sequence variation within a population.
I have no idea what I’m looking for… Can you give me more detail on what information Genome Browser has?
Physical location– Genome Browser allows you to view the location of your gene or sequence on the chromosome and zoom in or out to see its position relative to large and small elements around it (an element is a defined unit, like a gene, restriction enzyme site, or enhancer sequence, which can be marked upon the map of the chromosome). You may even get specific base pair coordinate numbers specific to the alignment version you have searched within. For information about the structure and packaging of a chromosome, look (here)
Genome by species– you can search the genomes of any of the many species genome alignments that have been uploaded, ranging from Human to White Rhinoceros.
Genes and gene predictions– These include exons, introns, and transcription direction (on the positive or negative strand). For more information on the elements of a gene, look (here).
mRNA and expression information– Genome Browser can align known mRNA transcripts to the gene sequence on the chromosome viewing window and provides information about gene expression patterns within various tissues and common cell cultures. For more information on transcription and translation look (here).
Regulation– This tool also maps epigenetic markers (such as CpG islands and marks on histone tails) and regulatory elements [such as transcription start sites (TSS)] to the sequence. For more information on gene expression and regulation look (here). For types of epigenetic marks look (here). For more information on sequence-based gene regulatory elements like enhancers, start (here).
Here are some questions I might want to use Genome Browser to answer:
Let’s say I’m studying the gene corticotropin releasing hormone (CRH).
(*hover over vocabulary like “exons” for links with further information on what this is)
- What does this gene look like on the sequence?
- Where are the exons and introns and how many are there?
- Which strand is the gene ‘read’ from during transcription?
- Where is the transcription start site (TSS)? Are there multiple transcription start sites?
- What is the actual DNA sequence of the gene?
- What is the GC content across a section of the sequence? (click here for a known sequence GC content calculator)
- What other genes are near your gene of interest?
- How is it expressed?
- What alternative RNA transcripts are known? (for an animation, look here)
- What are the CRH expression levels in various tissues? (more on dynamic gene expression)
- How is it regulated?
- Where are the relevant histone marks? (histone methylation, histone code)
- Are there any CpG islands on or near the gene?
- What transcription factors bind near this site?
- What does the gene encode?
- Do we know the function of the gene? (how to find the function of a gene) Is this a protein coding gene?
- What does the 3D structure of the protein look like?
- What differences do we see in sequence or regulation in other tissues or species?
- How well is the gene conserved between species? Are there regions of homology?
- Genome Browser provides some information for this, but other tools, such as the Evolutionary Conservation of Genomes Browser provide more detailed information if you already know the DNA sequence or location.
- Are there different histone marks in different cell lines? (histone methylation, histone code, cell culture)
- How well is the gene conserved between species? Are there regions of homology?
This article was created as a basic introduction to Genome Browser/BLAT and the kinds of questions you might come to this tool to answer. You can do much more with this tool than listed here. For a tutorial on the next level of using Genome Browser, check this post: “Genome Browser Tutorial Level 1”
