1. BIOL 3020 GENOMIC BIOLOGY LABORATORY 05A
OMIM Database & ENTREZ Gene
By Robert D. Locy, Fall 2015
(Go to the next tutorial oage: click).

2. Welcome to BIOL3020 Laboratories: Web-based Bioinformatics Tutorials designed to help you learn how to use the tools and databases located at the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) and the National Institutes of Health (HIH). To get Started open an NCBI Home page browser window ( <- Click here, and lets get started.
Welcome to BIOL3020 Laboratories: Web-based Bioinformatics Tutorials designed to help you learn how to use the tools and databases located at the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) and the National Institutes of Health (HIH). To get Started open an NCBI Home page browser window ( <- Click here, and subsequently return to this tutorial. (To go to the next frame click on the window, and lets get started.) (Go to the next tutorial oage: click).

3. Select [OMIM] in the drop down menu. Then click on [Search].
In previous labs, we briefly examined the Online Mendelian Inheritance in Man (OMIM) resource and the ENTREZ Gene resource at NCBI. Note that OMIM and Gene are probably the most useful sites at NCBI for mining genomic information and it’s relationship to human disease. To search for information concerning a particular gene or disease, an OMIM search can be run directly from the initial drop-down menu on the NCBI home page. Recall from previous tutorials that executed 'All Databases' searches and then selected OMIM database on the ENTREZ Search results page that subsequently comes up, but lets look at another more direct way to get to OMIM. (click) Begin by choosing [OMIM] in the drop down menu at the upper left of the NCBI home page as we did previously. Then without putting anything in the search window click [Search](click). (Go to the next tutorial oage: click).
In previous labs, we briefly examined the Online Mendelian Inheritance in Man (OMIM) resource and the ENTREZ Gene resource at NCBI. Note that OMIM and Gene are probably the most useful sites at NCBI for mining genomic information and it’s relationship to human disease. To search for information concerning a particular gene or disease, an OMIM search can be run directly from the initial drop-down menu on the NCBI home page. Recall from previous tutorials that executed 'All Databases' searches and then selected OMIM database on the ENTREZ Search results page that subsequently comes up, but lets look at another more direct way to get to OMIM. (click) Begin by choosing [OMIM] in the drop down menu at the upper left of the NCBI home page as we did previously. Then without putting anything in the search window click [Search](click). (Go to the next tutorial oage: click)

4. Click here learn more about other resources used by OMIM.
Click here and make notes on definitions and points about navigation of OMIM.
Click here learn more about other resources used by OMIM.
At this page you can (click) on [FAQ], and learn more about how OMIM works, and what some of the symbols mean. Then (click) on each of the [Related Resources] links on the right of the page. Particularly note the NCBI Gene resource that we will be using later in this tutorial. After you this, return to the NCBI home page, and search OMIM for pages about ‘Breast Cancer’ using instructions on the next page (click).
At this page you can (click) on [FAQ], and learn more about how OMIM works, and what some of the symbols mean. Then (click) on each of the [Related Resources] links on the right of the page. Particularly note the NCBI Gene resource that we will be using later in this tutorial. After you inspect these, return to the NCBI home page, and search OMIM for pages about ‘Breast Cancer’ using instructions on the next page (click).

5. Select OMIM in the drop down menu. Then click on [Search].
Breast Cancer
Select OMIM in the drop down menu.
Then click on [Search].
Type “Breast Cancer in the [Search] window.
To search for information concerning a particular gene or disease, an OMIM search can be run directly from the initial drop-down menu on the NCBI home page. Recall from previous tutorials that executed 'All Databases' searches and then selected OMIM database on the ENTREZ Search results page that subsequently comes up, but lets look at another more direct way to get to OMIM. (click) Begin by choosing [OMIM] in the drop down menu at the upper left of the NCBI home page as we did previously. Then without putting anything in the search window click [Search](click). (Go to the next tutorial oage: click).
To search for information concerning a particular gene or disease, an OMIM search can be run directly from the initial drop-down menu on the NCBI home page. Recall from previous tutorials that executed 'All Databases' searches and then selected OMIM database on the ENTREZ Search results page that subsequently comes up, but lets look at another more direct way to get to OMIM. (click) Begin by choosing [OMIM] in the drop down menu at the upper left of the NCBI home page. Then enter a search term such as 'Breast Cancer’ (click) and click [Search](click). (Go to the next tutorial oage: click).
To search for information concerning a particular gene or disease, an OMIM search can be run directly from the initial drop-down menu on the NCBI home page. Recall from previous tutorials that executed 'All Databases' searches and then selected OMIM database on the ENTREZ Search results page that subsequently comes up, but lets look at another more direct way to get to OMIM. (click) Begin by choosing [OMIM] in the drop down menu at the upper left of the NCBI home page as we did previously. Then type your search term (in our case let’s use “Breast Cancer” in the search window, and then click [Search](click). (Go to the next tutorial oage: click).

6. “*” Then click on [Search]. “%”
Breast Cancer AND (BROVCA* OR BRCA*)
You should find over 800 items in OMIM on breast cancer.
Then click on [Search].
“*”
“%”
Your OMIM search results page should look something like that given above. You should find over 800 items in OMIM on breast cancer (click). Inspect the entries you get, by scrolling down the page, and note that some accession numbers are preceded by an “*” (click), while others are preceeded by “#”, “%”, or “+” (click). These symbols designate the relative information found in each OMIM file. For example, entries that begin with: "*" are for genes of known sequence, "+" are genes with known sequence and phenotype, "#" describe phenotype, molecular basis known, and "%" mendelian phenotype or locus, molecular basis unknown. No symbol at the beginning designate a phenotype believed but not proven to have a molecular basis. A cursory look should indicate that we need to gain a little more organization of our page to make sense out of everything we obtained. Lets refine our search. This is easily done using the following syntax. [Breast Cancer AND (BROVCA* OR BRCA*)]. Type this in the search window (click) and hit [Search} again(click). Note using “AND” and “OR” in ALL CAPS formats them as connectors and not part of the search, and the use of *-wild cards is critical to making some searches work as you would like them to work. (Go to the next tutorial oage: click).
Your OMIM search results page should look something like that given above. You should find over 800 items in OMIM on breast cancer (click). Inspect the entries you get, by scrolling down the page, and note that some accession numbers are preceded by an “*” (click), while others are preceeded by “#”, “%”, or “+” (click). These symbols designate the relative information found in each OMIM file. For example, entries that begin with: "*" are for genes of known sequence, "+" are genes with known sequence and phenotype, "#" describe phenotype, molecular basis known, and "%" mendelian phenotype or locus, molecular basis unknown. No symbol at the beginning designate a phenotype believed but not proven to have a molecular basis. A cursory look should indicate that we need to gain a little more organization of our page to make sense out of everything we obtained. Lets refine our search. This is easily done using the following syntax. [Breast Cancer AND (BROVCA* OR BRCA*)]. Type this in the search window (click) and hit [Search} again(click). Note using “AND” and “OR” in ALL CAPS formats them as connectors and not part of the search, and the use of *-wild cards is critical to making some searches work as you would like them to work. (Go to the next tutorial oage: click).

7. On this new results page it should be easily possible to locate the results for BROVCA1, BROVCA2, BROVCA3, BROVCA4, BRCA1, BRCA2 AND BRCA3. Note the symbols in front of the accession numbers, and note the chromosomal locations of these genes. Can you make a hypothesis about the relationship of these OMIM entries based on your observations just on this page? Now go to several of the pages and determine if you can find further support for your hypothesis about these genes. Note that you may find it useful to right click on links and open them in new tabs or windows. You can then easily return to the search results page to look at other entries. Consider looking at BROVCA1 and BRCA1. The text in beginning of the OMIM page clearly indicates information you are looking for. The same is true for BROVCA2 and BRCA2. Pay particular attention to how the genes were mapped, and how they are now clinically detected. Note how the approaches we have learned about in class relate to the studies presented here. Also note how you can find information that is informative to novice OMIM users like us, and also useful to sophisocated healthcare users like physicians and pharmacists. This is a great example of this approach at NCBI. Return your browser to the NCBI homepage, and (Go to the next tutorial oage: click).
On this new results page it should be easily possible to locate the results for BROVCA1, BROVCA2, BROVCA3, BROVCA4, BRCA1, BRCA2 AND BRCA3. Note the symbols in front of the accession numbers, and note the chromosomal locations of these genes. Can you make a hypothesis about the relationship of these OMIM entries based on your observations just on this page? Now go to several of the pages and determine if you can find further support for your hypothesis about these genes. Note that you may find it useful to right click on links and open them in new tabs or windows. You can then easily return to the search results page to look at other entries. Consider looking at BROVCA1 and BRCA1. The text in beginning of the OMIM page clearly indicates information you are looking for. The same is true for BROVCA2 and BRCA2. Pay particular attention to how the genes were mapped, and how they are now clinically detected. Note how the approaches we have learned about in class relate to the studies presented here. Also note how you can find information that is informative to novice OMIM users like us, and also useful to sophisocated healthcare users like physicians and pharmacists. This is a great example of this approach at NCBI. Return your browser to the NCBI homepage, and (Go to the next tutorial oage: click).

8. Type brca1 into the search window, and click on [Search].
From any OMIM Search Resuls page where you have been, let’s type [brca1] into the search window (click). Then (click) [Search] and wait for the OMIM search results page to come up. To go to the next page of the tutorial: (click).
From any OMIM Search Resuls page where you have been, let’s type [brca1] into the search window (click). Then (click) [Search] and wait for the OMIM search results page to come up. To go to the next page of the tutorial: (click).

9. On this new results page it should be easily possible to locate the results for BRCA1 and all other OMIM accessions that contain BRCA1 in the name or file. Recall that we looked at other resources that could be obtained from OMIM. Most important of these is the ENTREZ Gene page. This page can be directly accessed for any hit on OMIM Search Results page in several ways, but the quickest and easiest is to simply click on the [Gene summaries] link found beneath each hit (click). This takes you to any Gene page that exists at NCBI for the accessions in OMIM. Note that there are other resources that are directly accessible by these links with each accession. A second way to find the gene page and other resources is to put a check in the box next to the gene(s) you wish to search for (click), and then look at the look for the resource you wish to find in the [Database] drop down (click) under [Find related data]. Select [Gene] for example, but note the other databases that are directly linked to NCBI; (click) [Find items] to negotiate to gene or other resources in this way. like us, and also useful to sophisocated users. (Go to the next tutorial page: click).
On this new results page it should be easily possible to locate the results for BRCA1 and all other OMIM accessions that contain BRCA1 in the name or file. Recall that we looked at other resources that could be obtained from OMIM. Most important of these is the ENTREZ Gene page. This page can be directly accessed for any hit on OMIM Search Results page in several ways, but the quickest and easiest is to simply click on the [Gene summaries] link found beneath each hit (click). This takes you to any Gene page that exists at NCBI for the accessions in OMIM. Note that there are other resources that are directly accessible by these links with each accession. A second way to find the gene page and other resources is to put a check in the box next to the gene(s) you wish to search for (click), and then look at the look for the resource you wish to find in the [Database] drop down (click) under [Find related data]. Select [Gene] for example, but note the other databases that are directly linked to NCBI; (click) [Find items] to negotiate to gene or other resources in this way. like us, and also useful to sophisocated users. (Go to the next tutorial page: click).

10. You should now be at the human BRCA1 Gene page for the BRCA1 gene
You should now be at the human BRCA1 Gene page for the BRCA1 gene. (You may need to type “BRCA1” in the search window (while at Gene) and click on search.) At the top of the page you should see the title (click) with a summary of the information on the page immediately underneath. Your page may look slightly different berneath the summary, but if you (click) on the dropdown buttons on the left of each of the links they will toggle to and from the condensed from shown above. There is also a Table of Contents to the right and many other links that you may find useful. You may want to look at some of these in the future. Note that right now much of the detailed information on a Gene page is beyond or experience base, but look for and note things that are familiar as you go through each facet of the page. A detailed summary of the sections of a gene page and using a Gene search can be found on the NCBI Gene Fact Sheet (Go to the next tutorial page: click).
You should now be at the human BRCA1 Gene page for the BRCA1 gene. (You may need to type “BRCA1” in the search window (while at Gene) and click on search.) At the top of the page you should see the title (click) with a summary of the information on the page immediately underneath. Your page may look slightly different berneath the summary, but if you (click) on the dropdown buttons on the left of each of the links they will toggle to and from the condensed from shown above. There is also a Table of Contents to the right and many other links that you may find useful. You may want to look at some of these in the future. Note that right now much of the detailed information on a Gene page is beyond or experience base, but look for and note things that are familiar as you go through each facet of the page. A detailed summary of the sections of a gene page and using a Gene search can be found on the NCBI Gene Fact Sheet (Go to the next tutorial page: click).

11. The [Genomic context] section shows you information about the gene in the genome. This includes the gene location (click), and a link to the NCBI Map viewer is also given in the top right (click). Note that for this gene there is also a link to a map on the [Epigonomics] page. Right click on the MapViewer link and look at the map that you are given to see the BRCA1 gene in a broad chromosomal context. Beneath these links a description of the genome assembly that is being used and the location of the specific gene under consideration is given (click), Beneath that a blow up of the local region of the chromosome showing the gene of interest ( in red) and other genes in the region can also be seen (click). Note that different Gene pages may have slight variations on this theme, but that you now have a lot of useful information about your gene quickly referenced at this site. After exploring this section links (Go to the next tutorial page: click).
The [Genomic context] section shows you information about the gene in the genome. This includes the gene location (click), and a link to the NCBI Map viewer is also given in the top right (click). Note that for this gene there is also a link to a map on the [Epigonomics] page. Right click on the MapViewer link and look at the map that you are given to see the BRCA1 gene in a broad chromosomal context. Beneath these links a description of the genome assembly that is being used and the location of the specific gene under consideration is given (click), Beneath that a blow up of the local region of the chromosome showing the gene of interest ( in red) and other genes in the region can also be seen (click). Note that different Gene pages may have slight variations on this theme, but that you now have a lot of useful information about your gene quickly referenced at this site. After exploring this section links (Go to the next tutorial page: click).

12. The [Genomic regions, transcript, and products]section shows you more detailed information about the gene in the genome. Specifically, about the transcripts produced, and gives hyperlinks to other databases at NCBI containing sequence information. Scroll down and note the types of information you can find. We will return to discuss what is here more fully in later labs, but for now, note that the Gene page is organized around so called reference sequences (refseq). These are highly annotated sequences for each gene, and you can quickly move to the refseq part of the Gene page by clicking on the hyperink in the upper right. Go to your browser and do that, then return here and (Go to the next tutorial page: click).
The [Genomic regions, transcript, and products]section shows you more detailed information about the gene in the genome. Specifically, about the transcripts produced, and gives hyperlinks to other databases at NCBI containing sequence information. Scroll down and note the types of information you can find. We will return to discuss what is here more fully in later labs, but for now, note that the Gene page is organized around so called reference sequences (refseq). These are highly annotated sequences for each gene, and you can quickly move to the refseq part of the Gene page by clicking on the hyperink in the upper right. Go to your browser and do that, then return here and (Go to the next tutorial page: click).

13. The [The NCBI Reference Sequences (RefSeq)]section shows you Information about the RefSeq in the genome, and about known mRNA and protein sequences related to it. The Genomic RefSeq (click) is the one that would be considered the fully functional (wild type) sequence. Underneath that you find the mRNA sequences (click) for variant genes called isoforms (click) and proteins (click) that have been characterized. Note that this format can be repeated several times (once for each known isoform) as you scroll down the page. Go to your browser and locate the [The NCBI Reference Sequences (RefSeq)] that looks like that shown above. Click on the hyperlinks associated with the arrows shown, and examine the content in this section. Then locate the top of the page symbol, and (click) on that. Return here and (Go to the next tutorial page: click).
The [The NCBI Reference Sequences (RefSeq)]section shows you Information about the RefSeq in the genome, and about known mRNA and protein sequences related to it. The Genomic RefSeq (click) is the one that would be considered the fully functional (wild type) sequence. Underneath that you find the mRNA sequences (click) for variant genes called isoforms (click) and proteins (click) that have been characterized. Note that this format can be repeated several times (once for each known isoform) as you scroll down the page. Go to your browser and locate the [The NCBI Reference Sequences (RefSeq)] that looks like that shown above. Click on the hyperlinks associated with the arrows shown, and examine the content in this section. Then locate the top of the page symbol, and (click) on that. Return here and (Go to the next tutorial page: click).

14. Inspect the table of contents
Inspect the table of contents. Note that there are many resources here that we have not yet investigated. You may want to browse these when you have a specific problem to approach, and discussion with the TA may assist you in finding what you are looking for. Two sections that we need to look at more are the [Phenotypes] (click) and [Variation] (click) sections. The next two tutorial pages will show you what to look for at each of these two sections. Go to your browser, and click on [Phenotypes]. Then return here and (Go to the next tutorial page: click).

15. At the [Phenotypes] section of the Gene Page, information concerning the phenotypes caused by variants in the gene are shown. The information on this page would be the types of information found in OMIM, and you can locate links to OMIM pages on this page (click). At the top of the section are links to the Genetic Testing Registry at NCBI (click) and the eQTL and phenotypic association data (click) for the gene. Go to your browser, and examine these resources. How to these compare with other mapping resources you are aware of for SNP data and phenotype associations? Now go to the Variations section of the Gene Page. Return here and (Go to the next tutorial page: click).
At the [Phenotypes] section of the Gene Page, information concerning the phenotypes caused by variants in the gene are shown. The information on this page would be the types of information found in OMIM, and you can locate links to OMIM pages on this page (click). At the top of the section are links to the Genetic Testing Registry at NCBI (click) and the eQTL and phenotypic association data (click) for the gene. Go to your browser, and examine these resources. How to these compare with other mapping resources you are aware of for SNP data and phenotype associations? Now go to the Variations section of the Gene Page. Return here and (Go to the next tutorial page: click).

16. At the [Variation] section of a Gene page you can find links to databases that organize both SNP and other types of polymorphic molecular markers. The two most useful of these pages are the NCBI dbVar database (click) that lists all types of variations, and the NCBI dbSNP database (click) that houses information about SNPs. In your browser. Go to your browser, and click on [Variations] in the table of contents, and then examine the resources at dbVar and dbSNP for the BRCA1 gene. Then return here and (Go to the next tutorial page: click).
At the [Variation] section of a Gene page you can find links to databases that organize both SNP and other types of polymorphic molecular markers. The two most useful of these pages are the NCBI dbVar database (click) that lists all types of variations, and the NCBI dbSNP database (click) that houses information about SNPs. In your browser. Go to your browser, and click on [Variations] in the table of contents, and then examine the resources at dbVar and dbSNP for the BRCA1 gene. Then return here and (Go to the next tutorial page: click).

17. SUMMARY
This tutorial should have shown you the extensive resources at NCBI. The databases are interlinked, and it is possible to readily move between databases to mine all types of data from NCBI. Once you have found the gene that you are interested from either from an ENTREZ search or an OMIM search, you should now be able to navigate to: 1) find the RefSeq for the gene and all important variants; 2) nucleotide sequence; 3) protein sequence; 4) gene location (chromosome and position); 5) map view of that location; 6) all variations in dbVAR, 7) all SNPs located in the gene and its vicinity, and 7) the available Genetic Tests for disease-causing variations. And this is not all of the information we can locate in this way. As we become more sophistocated genomic biologists we will find much more information of use concerning how the gene works/doesn’t work leading to the diseased state, but for now we have established that the resources available at NCBI for Mendelian Genes have revolutionized Population and Quantitative genetics in humans.
Similar resources are available for many organisms at this point. Although each organism may have it’s own unique databases, the fundamental approach being employed by modern biologists is consistent across a wide variety of organisms ranging from pathogenic microorganisms to fungi, and plants as well as model and non-model animals.
END LABORATORY 05A