# Presentation: 674320

## Sequences, Literatures, And More - Resources and tools from NCBI

**Tao Tao, May 8, 2007****	****	****	****NCBI, NLM, NIH**

## About NCBI (housekeeping materials)
Databases from NCBI
Power of connection:
		interlinking records from different databases
Database querying with Entrez
Literature, sequence, gene, and disease resources
		with example searches
NCBI tools: BLAST, cdd, and Cn3D
with example searches

**Databases from NCBI**
**Power of connection:**
**	****	****interlinking records from different databases**
**Database querying with *****Entrez***
**Literature, sequence, gene, and disease resources**
**	****	****with example searches**
**NCBI tools: BLAST, cdd, and Cn3D**
**with example searches**

- Topics

**Notes:**
First part will cover an introduction to the NCBI- who we are and what we do- and to our resources, including our primary nucleotide database GenBank, as well as the other primary and secondary databases, such as protein, structure and taxonomy databases.  Database make-up and format.   Databases are searcheable in Entrez, our search and retrieval system.  How Entrez works, its features and enhanced search options and it’s Linking functionality.  Last part will utilize an example of a search conducted in Entrez.

## NCBI: The National Center for Biotechnology Information

- Created by US Congress in 1988, NCBI is part of the
- National Library of Medicine at National Institutes of Health.
- Its mandates are to:
- establish public databases
- perform researches in computational biology
- develop software tools for sequence analysis
- disseminate biomedical information to the public

## Organization Structure

**Organization Structure**

## Web Access to NCBI Resources

**Web Access to NCBI Resources**

**Through NCBI home page at:**
- _[www.ncbi.nlm.nih.gov](http://www.ncbi.nlm.nih.gov/)_

**Free to all !!**

**Notes:**
NCBI homepage.  Logo will take you back to home page.
About NCBI provides introduction to the NCBI and contains basic information on genetics and bioinformatics.

## NCBI Web Traffic: increase over the past few years

## Educational & Training Resources

**NCBI Training Courses**** **
**Field Guide**
**	****General introduction to NCBI resources**
**Field Guide Plus ***
**	****Extended version with better hands on**
**MiniCourses**
**	****Database/Task specific short courses**
** ****Medical Library Association Course**
**	****Course specific for the librarians**
**PowerTools Technical Workshop Series ***
**	****focusing on scripting for people with the **
**	****technical know-how and advanced need**
**** Taught only at NCBI***

**http://www.ncbi.nlm.nih.gov/Education/**

**Notes:**
Education page.  Links to course information and online tutorials and NCBI handbook.

## Asking For Help When Needed

**NCBI logo **
**	****	****	****	****Reset by bringing you **
**	****	****	****	****back to NCBI home page **
**Sitemap (Alphabetical List)**
**	**_[SITE MAP_x000b_](http://www.ncbi.nih.gov/Sitemap/index.html)__[Alphabetical List](http://www.ncbi.nih.gov/Sitemap/AlphaList.html)_** ******** ****useful when you know the name of the resources**
**	**_[Resource Guide](http://www.ncbi.nih.gov/Sitemap/ResourceGuide.html)_
**Search “****NCBI Web site****” as target database**
**Useful when resource name is unknown**
**Contact user services at:**
**info@ncbi.nlm.nih.gov **
**(301)496-2475**
**Personal consultation (research project oriented):**
- _[www.ncbi.nlm.nih.gov/staff/tao/](http://www.ncbi.nlm.nih.gov/staff/tao/)_** **

## Entrez System

## Entrez Databases: Tight Integration

- Hard Link

**3 -D Structure**

**Nucleotide**
**Sequences**

**Protein**
**Sequences**

**Taxonomy**

**PubMed**
**Abstracts**

## The Entrez System: Extensive Linking

**“****Definition” of *****Entrez*****:**
**Entrez**** is based on relational databases. It is a system to index complex records and interlink them according to their indexed properties. **
**Entrez**** is also a tool to efficiently search and retrieve specific records from this collection.**
***Through my colored “lens”***
***No quoting please :-)***

## Sequence Databases: Primary vs. Derivative

**Sequence Databases:**** ****Primary**** vs. ****Derivative**

**Notes:**
~11,000 sequences are submitted per day.

## GenBank: NCBI’s Primary Sequence Database

**Nucleotide only sequence database **
**Archival in nature**
**Historical**
**Subjective: submitter’s view**
**Redundant**
**GenBank data sources**
**Direct submissions **
**Batch: EST, GSS, STS**
**ftp upload (genome data)**
**Three collaborating databases**
**GenBank (77.6%)**
**DDBJ (14.1%)**
**EMBL (8.3%)**

**EST****	****Expressed Sequence Tag **
**GSS****	****Genome Survey Sequence**
**HTG****	****High Throughput Genomic**
**STS****	****Sequence Tagged Site**
**HTC****	****High Throughput cDNA**
**PAT****	****Patent**

**PRI****	****primate **
**PLN****	****plant and fungal**
**BCT****	****bacterial and archeal **
**INV****	****invertebrate**
**ROD****	****rodent**
**VRL****	****viral**
**VRT****	****other vertebrates**
**MAM****	****mammalian **
**PHG****	****phage**
**SYN****	****synthetic (cloning vectors) **
**UNA****	****un-annotated**

## Public Sequence Databases: three sources

**Public Sequence Database **
**(pooled from three sources)**

**Public Sequence Databases: ****three sources**

| Query Term * | Nucleotide | Protein |
| --- | --- | --- |
| srcdb_genbank[prop] | 75356092 (77.6%) | 7156916 (83.8%) |
| srcdb_ddbj[prop] | 13658841 (14.1%) | 492336 (5.8%) |
| srcdb_embl[prop] | 8070899 (8.3%) | 894779 (10.4%) |
| Total | 97085832 | 8544031  |

***Primary sequences only. Data from April 13, 2007.***

## GenBank: growing exponentially

**Sequence Records**
**(millions)**

**Total Base Pairs**
**(billions)**

- Latest Dataset
- Release 155:    65.1 million records
- 		   65.4 billion nucleotides
- Average doubling time ≈ 14 months*

***(Data from September 2006)***

**Notes:**
Doubling time is currently less than 1 year and still accelerating.

## RefSeq: NCBI’s Derivative Sequence Database

**Curated transcripts and proteins (****NM_, NP_****)**
**reviewed**
**Most model organisms and more**
**Model transcripts and proteins (****XM_, XP_****)**
**Assembled Genomic Regions (contigs) (****NT_, NW_****)**
**higher genomes**
**Chromosome records (****NC_****)**
**Higher genomes**
**Microbial genomes**
**Organelle genomes**

- ftp://ftp.ncbi.nih.gov/refseq/release/

**srcdb_refseq[Properties]**

**Benefits :**
**non-redundant    **
**explicitly linked nucleotide and protein sequences**
**regular update**
**validated data **
**consistent format **
**distinctive accession series **
**stewardship by NCBI staff and collaborators**

**Notes:**
Goal= nonredundant set of genes/proteins for each organism represented
Model= comes from analysis of genomic content from organism assembly
Reannotation of microbial genomes, for example.

## Sequence Record: different formats

**Sequence records are kept in ASN.1 format.**
**They are translated “on the fly” to others upon request.**

** ****GenBank/GenPept****	*****useful for scientists****** ***
** ****FASTA****	****	****	*****the simplest format ***
** ****ASN.1****	****	****	*****useful for programmers***
** ****XML****	****	****	*****useful for programmers***

## Other Entrez Databases

** ****Gene:****	****	****Gene centric records**
** ****PubMed****:****	****	****Biomedical literatures**
** **
** ****OMIM****:**** ****	****	****Genetic disorder/phenotype**
** ****Structure****:**** ****	****Structures (PDB)**
**	****Cn3D viewer, NCBI curation**
** ****CDD:**** ****	****	****Conserved Domain Database**
**	****Protein families (COGs)**
**	****Single domains (PFAM, SMART, CD)**
** ****SNP:****	****	****Nucleotide Polymorphism**

## Using the Entrez System

## Global Entrez: Overview of the database landscape

**Human ****[organism]**

**All**** [filter]**

***As of April 13, 2007***

**Notes:**
Entrez Global.  Number of records present in each one of those databases.  

## Entrez Databases: Search with  Boolean Operator Connected Text Terms

**Entrez Databases:**** *****Search with  Boolean Operator Connected Text Terms***

**Query terms are searched against “All Databases” by default**
**Terms are boolean ****AND****’ed by default**
**Other operators need to be specified explicitly with ****OR****, ****NOT**
**Forced phrase search needs to be quoted**
**Field limiter makes the search more specific**

## Entrez Databases: Literatures 

**PubMed:**** mostly abstracts from over ****50K**** journals**
**PMC:**** full text article, close to ****300**** journals**
**Books:**** indexed book chapters from over ****40**** titles with over ****150K**** entries**
**OMIM:**** over ****17K**** human genetic disorders/phenotypes**
**Suggestions:**
**	****- Get more specific records using limiter such as**
**	****	****[au]****, ****[ptyp]****, ****[mesh]****, ****[pdat]****, and ****[title]**
**	****- Explore the field limiter using “****Preview/Index****” tab**
**	****- Combine different sets of results using “****History****” tab**
**	****- See the term mapping using “****Details****” tab**

***Example: Nematode microarray in pubmed, first hit, book link, RNAi, first book, first section***

## Entrez Literature Databases: Sample search

***PubMed to PMC with Free PDF***
** ****Search with **_[restriction-modification system](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system)_
** ****Refine it by adding  **_[AND](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system+AND+regulation)__[ regulation ](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system+AND+regulation)_
** ****Find specific articles by adding:**** **_[AND](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system+AND+regulation+AND+Blumenthal+RM%5Bau%5D)__[ Blumenthal ](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system+AND+regulation+AND+Blumenthal+RM%5Bau%5D)__[RM[au](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system+AND+regulation+AND+Blumenthal+RM%5Bau%5D)__[]](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=search&term=restriction-modification+system+AND+regulation+AND+Blumenthal+RM%5Bau%5D)_
** ****Click “****Free in PMC”****, what do we get there?**
** ****Click ****“Cited in PMC”**** to see the other papers**

## Entrez Databases: sequence  gene  disease

**Search for sequences:**
** ****Search with **_[phenylalanine ](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=nuccore&cmd=search&term=%22phenylalanine+hydroxylase%22)__[hydroxylase](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=nuccore&cmd=search&term=%22phenylalanine+hydroxylase%22)__[ ](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=nuccore&cmd=search&term=%22phenylalanine+hydroxylase%22)_
** ****click ****RefSeq ****tab and the tack to get only refseq entries**
** ****click ****mRNAs ****tab and the tack to get only mRNA entries**
** ****Use field limit to get only ****human**** entries (*****AND human[orgn]*****)**
** ****Getting the ****Gene**** record through ****Links**
** ****Getting the genetic disorder information in ****OMIM**** through ****Links**** **
** **

## Gene: a much preferred entry point

**Entrez Gene provides:****	**
_**Summary information plus Direct access to**_** ****	**
** ****RefSeq mRNA, Protein, Genomic entries**
** ****Key publications**
** ****Domain, BLink **
** ****OMIM, UniGene, other Linkouts**
_**& access through links**_
**HomoloGene, SNPs, MapViewer, KEGG, and more ...**
**The detour through Gene is an effective short cut even if you are looking for sequences.**

**Gene ****vs**** ****direct search**
**Line**** vs ****network**
**Linear**** vs ****geomtric**
**shotgun**** vs ****rifle**

## NCBI Tools

**BLAST**
**Cn3D**
**Splign, Spidey**
**MapViewer**
**AceView**
**etc**

**BLAST: a sequence comparison tool used to:**
***Identify sequence***
**Cluster sequences from the same gene**
**Find related or similar sequences**
**Map mRNA to its genomic counterpart**
***Verify primer annealing site***
***Identify functional domain***

## BLAST: identify unknown sequence

**AGGTCGGCCACGCCACTCGCGGGTGGGCTCGTGTTACAGCACACCAGCCCGTTCTTTTCCCCCCCTCCCA**
**CCCTTAGTCAGACTCTGTTACTTACCCGTCCGACCACCAACTGCCCCCTTATCTAAGGGCCGGCTGGAAG**
**ACCGCCAGGGGGTCGGCCGGTGTCGCTGTAACCCCCCACGCCAATGACCCACGTACTCCAAGAAGGCATG**
**TGTCCCACCCCGCCTGTGTTTTTGTGCCTGGCTCTCTATGCTTGGGTCTTACTGCCTGGGGGGGGGGAGT**
**GCGGGGGAGGGGGGGTGTGGAAGGAAATGCACGGCGCGTGTGTACCCCCCCTAAAGTTGTTCCTAAAGCG**
**AGGATACGGAGGAGTGGCGGGTGCCGGGGGACCGGGGTGATCTCTGGCACGCGGGGGTGGGAAGGGTCGG**
**GGGAGGGGGGGATGGAGTACCGGCCCACCTGGCCGCGCGGGTGCGCGTGCCTTTGCACACCAACCCCACG**
**TCCCCCGGCGGTCTCTAAGAAGCACCGCCCCCCCTCCTTCATACCACCGAGCATGCCTGGGTGTGGGTTG**
**GTAACCAACACGCCCATCCCCTCGTCTCCTGTGATTCTCTGGCTGCACCGCATTCTTGTTTTCTAACTAT**
**GTTCCTGTTTCTGTCTCCCCCCCCCCCACCCCTCCGCCCCACCCCCCAACACCCACGTCTGTGGTGTGGC**
**CGACCCCCTTTTGGGCGCCCCGTCCCGCCCCGCCACCCCTCCCATCCTTTGTTGCCCTATAGTGTAGTTA**
**ACCCCCCCCGCCCTTTGTGGCGGCCAGAGGCCAGGTCAGTCCGGGCGGGCAGGCGCTCGCGGAAACTTAA**
**CACCCACACCCAACCCACTGTGGTTCTGGCTCCATGCCAGTGGCAGGATGCTTTCGGGGATCGGTGGTCA**
**GGCAGCCCGGGCCGCGGCTCTGTGGTTAACACCAGAGCCTGCCCAACATGGCACCCCCACTCCCACGCAC**
**CCCCACTCCCACGCACCCCCACTCCCACGCACCCCCACTCCCACGCACCCCCACTCCCACGCACCCCCAC**
**TCCCACGCACCCCCACTCCCACGCACCCCCACTCCCACGCACCCCCACTCCCACGCATCCCCGCGATACA**
**TCCAACACAGACAGGGAAAAGATACAAAAGTAAACCTTTATTTCCCAACAGACAGCAAAAATCCCCTGAG**
**TTTTTTTTTATTAGGGCCAACACAAAAGACCCGCTGGTGTGTGGTGCCCGTGTCTTTCACTTTTCCCCTC**
**CCCGACACGGATTGGCTGGTGTAGTGGGCGCGGCCAGAGACCACCCAGCGCCCGACCCCCCCCTCCCCAC**
**AAACACGGGGGGCGTCCCTTATTGTTTTCCCTCGTCCCGGGTCGACGCCCCCTGCTCCCCGGACCACGGG**
**TGCCGAGACCGCAGGCTGCGGAAGTCCAGGGCGCCCACTAGGGTGCCCTGGTCGAACAGCATGTTCCCCA**
**CGGGGGTCATCCAGAGGCTGTTCCACTCCGACGCGGGGGCCGTCGGGTACTCGGGGGGCATCACGTGGTT**
**ACCCGCGGTCTCGGGGAGCAGGGTGCGGCGGCTCCAGCCGGGGACCGCGGCCCGCAGCCGGGTCGCCATG**
**TTTCCCGTCTGGTCCACCAGGACCACGTACGCCCCGATGTTCCCCGTCTCCATGTCCAGGATGGGCAGGC**
**AGTCCCCCGTGATAGTCTTGTTCACGTAAGGCGACAGGGCGACCACGCTAGAGACCCCCGAGATGGGCAG**
**GTAGCGCGTGAGGCCGCCCGCGGGGACGGCCCCGGAAGTCTCCGCGTGGCGCGTCTTCCGGGCACACTTC**

**BLAST: ****identify unknown sequence**

***Source sequence: >gi|9629378:c6907-4953***

**PCR fragment amplified from a clinical sample**
**Search:**
**Copy the sequence**
**Go to **_[www.ncbi.nih.gov/BLAST/](http://www.ncbi.nih.gov/BLAST/)_
**Select “blastn” **
**Paste the sequence in the first large input box**
**Change database to nt by clicking “others”**
**Click “BLAST!” button to search**
**Get Result:**
**The page will automatically check for result**
**Analyze:**
**See the matching sequences returned to **
**determined the identification/source**
**Preserved search result under: **
**1158860095-5488-172146079962.BLASTQ1**** **

## BLAST: search steps  

***Source sequence: >gi|9629378:c6907-4953***

## BLAST: Search results

## BLAST: interpreting the result

**The matches are all from *****Herpes Simplex Virus, *****strongly indicating query’s viral origin.**
**The patient will be diagnosed as HSV infected, even though he/she shows no sign of infection.**
***Biology:***
***	******Once infected, the virus stays with host for life and periodically reemerge (cold sore). During latent stage, the viral genome is kept as an episome.  The LAT region of the genome is transcribed during this stage. The presence of this transcript indicates HSV infection.***

## BLAST: mapping primer to the human genome

**Go to this page:**
- _[http://www.ncbi.nlm.nih.gov/genome/seq/BlastGen/BlastGen.cgi?taxid](http://www.ncbi.nlm.nih.gov/genome/seq/BlastGen/BlastGen.cgi?taxid=9606)__[=9606](http://www.ncbi.nlm.nih.gov/genome/seq/BlastGen/BlastGen.cgi?taxid=9606)_

**Upstream primer       5 ́-CCATGGCGACCCTGGAAAAGC-3 ́****Downstream primer     5 ́-CAGCAGCGGCTGTGCCTGCGG-3 ́ **

**Adjustments needed:**
** ****Paste in converted primers**
** ****Change database to: genome (reference only)**
** ****Change program to blastn**
** ****Change filter to “None”**
** ****Increase Expect to 10**
** ****Hit submit to search**
**Information from such a search:**
** ****- Find the genomic location**
** ****- Check for secondary annealing sites**
** ****- Identify target gene**
** ****- See amplicon sequence and feature**
** ****- Link to other resources with additional info **

**See the adjusted page with input**
**saved **_[result](http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?CMD=Get&RID=1158868277-7114-15686947375.BLASTQ1)__ for this search._

## BLAST : sample domain search

**>Transmembrane Protein**
**MLKIITRQLFARLNRHLPYRLVHRDPLPGAQTAVNATIPPSLSERCLKVAAMEQETLWRVFDTHPEGLNA**
**AEVTRAREKHGENRLPAQKPSPWWVHLWVCYRNPFNILLTILGGISYATEDLFAAGVIALMVGISTLLNF**
**VQEARSTKAADALKAMVSNTATVLRVINENGENAWLELPIDQLVPGDIIKLAAGDMIPADLRIIQARDLF**
**VAQASLTGESLPVEKVAATREPRQNNPLECDTLCFMGTNVVSGTAQAVVMATGAGTWFGQLAGRVSEQDN**
**EQNAFQKGISRVSMLLIRFMLVMAPVVLIINGYTKGDWWEAALFALSVAVGLTPEMLPMIVTSTLARGAV**
**KLSKQKVIVKHLDAIQNFGAMDILCTDKTGTLTQDKIVLENHTDISGKPSEHVLHCAWLNSHYQTGLKNL**
**LDTAVLEGVDETAARQLSGRWQKIDEIPFDFERRRMSVVVAEDSNVHQLVCKGALQEILNVCTQVRHNGD**
**IVPLDDNMLRRVKRVTDTLNRQGLRVVAVATKYLPAREGDYQRIDESDLILEGYIAFLDPPKETTAPALK**
**ALKASGITVKILTGDSELVAAKVCHEVGLDAGDVIIGSDIEGLSDDALAALAARTTLFARLTPMHKERIV**
**TLLKREGHVVGFMGDGINDAPALRAADIGISVDGAVDIAREAADIILLEKSLMVLEEGVIEGRRTFSNML**
**KYIKMTASSNFGNVFSVLVASAFLPFLPMLPLHLLIQNLLYDVSQVAIPFDNVDEEQIQKPQRWNPADLG**
**RFMVFFGPISSIFDILTFCLMWWVFHANTPETQTLFQSGWFVVGLLSQTLIVHMIRTRRLPFIQSRAAWP**
**LMAMTLLVMVVGVSLPFSPLASYLQLQALPLSYFPWLIAILVGYMTLTQLVKGFYSRRYGWQ**

***gi|543864|sp|P36640|ATMA_SALTY***

**Search:**
**Copy the sequence**
**Go to **_[http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi](http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi)_
**Paste the sequence in “Query” box**
**Click “Submit Query” button to get the result**
**Analysis:**
**See the cartoon to get the summary**
**Click on cartoon of interest to see details**

## BLAST: CDD search result analysis

**BLAST: ****CDD search result analysis**

***Hydrolase domain (partial match)***
**Click the cartoon to go to domain record**
**Click on “Show Structure” **
**This launches ****Cn3D**** to display the structure with sequence alignment**
***MgtA Domain (first match to the “whole” query)***
**Covering the whole domain**
**Highly conserved, broken into segments (with 10-membrane domains)**

**It is important to master the power of this interlinked collection of resources, which may allow you to see that hidden pot of *****virtual***** ****gold ...**

**See the actual **_[result](http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?seqinput=P36640&Database=cdd)__._

## Other Databases & Tools

**Databases:**
**Small molecules: ****PubChem**** Compound, Substance, BioAssey**
**Expression: ****GEO**** dataset, GEO profile**
**Large Scale genetic study: ****dbGAP**
**SNP****: single nucleotide polymorphism, haplotype, gentype**
**Probe****: Probes, RNAi, primers**
**Tools:**
**Splign**** (exon/intron boundary mapping)**
**Genome Workbench**

## Outside Tools: complementing NCBI Resources

**Tools for membrane domain, signal peptide prediction:**
- _[http://www.ch.embnet.org/software/TMPRED_form.html](http://www.ch.embnet.org/software/TMPRED_form.html)_
- _[http://www.cbs.dtu.dk/services/SignalP/](http://www.cbs.dtu.dk/services/SignalP/)_
**Tools for multiple sequence alignment:**
- _[http://bioinfo.genopole-toulouse.prd.fr/multalin/multalin.html](http://bioinfo.genopole-toulouse.prd.fr/multalin/multalin.html)_
**http://www.drive5.com/muscle/**
**http://www.ebi.ac.uk/clustalw/ **
**Tools for transcriptional factor binding sites identification:**
- _[http://](http://www.cbil.upenn.edu/tess/)__[www.cbil.upenn.edu/tess](http://www.cbil.upenn.edu/tess/)__[/](http://www.cbil.upenn.edu/tess/)_
- _[http://motif.genome.jp/](http://motif.genome.jp/)_
**Tools for transcriptional factor binding sites identification:**
- _[http://bioinformatics.org/sms2/](http://bioinformatics.org/sms2/)_
**Tools for restriction mapping:**
- _[http://rna.lundberg.gu.se/cutter2/](http://rna.lundberg.gu.se/cutter2/)_
- _[http://tools.neb.com/NEBcutter2/index.php](http://tools.neb.com/NEBcutter2/index.php)_** **

## Examples To Try on Your Own

***As self-paced exercises, students can try:***
***hexosaminidase A***** : **
**absent in children with Tay-Sachs disease**
***peroxisomal targeting signal import receptor (PXR1)*****: **
**absent in *****Zellweger***** syndrome**** **
***Glucocerebrosidase:***** **
**not made in patients with Gaucher disease**
***HBB*****: **
**certain mutation results in Sickle Cell Anemia**
***PRNP*****: **
**Prion gene implicated in “mad cow” like brain disorder in human**

## Source Of Help When Needed

- NCBI User Service
- 	info@ncbi.nlm.nih.gov
- 	blast-help@ncbi.nlm.nih.gov
- 	(301)496-2475
- Help Session for NIH staff
- 	http://www.ncbi.nlm.nih.gov/staff/tao/