Prion Protein

Group Members

• Bilal• Azraar• Kosala• Menaka• Milan

Retrieve human entries related to "prion protein" in Entrez Gene.

Identify the gene for prion protein

• PRNP

Name the map location of this gene on the human genome.

The human PRNP gene is located on the short (p) arm of chromosome 20 between the end (terminus) of the arm and position 12, from base pair 4,615,068 to base pair 4,630,233.

As given in ENTREZ database: NC_000020.11 (4686151..4701588)

What is the function of this protein?

• PRNP gives instructions to make prion protein (PrP), which is active in the brain and several other tissues.

• Can occur in two forms called PrP-sen and PrP-res.

• Exact function these is not defined, but believed its involved in communication between neurons, cell death, and controlling sleep patterns.

• Includes the transport of copper into cells and protection of brain cells (neurons) from injury (neuroprotection)

http://ghr.nlm.nih.gov/gene/PRNP

Few functions as defined in NCBI

• ATP-dependent protein binding • chaperone binding • copper ion binding • copper ion binding• identical protein binding• microtubule binding• protein binding• tubulin binding

http://www.ncbi.nlm.nih.gov/gene/5621

Phenotypes associated with the mutations in this gene.

• Kuru• Fatal familial insomnia• Creutzfeldt–Jakob disease (CJD)• Iatrogenic Creutzfeldt–Jakob disease (iCJD)• Variant Creutzfeldt–Jakob disease (vCJD)• Familial Creutzfeldt–Jakob disease (fCJD)• Sporadic Creutzfeldt–Jakob disease (sCJD)• Gerstmann–Sträussler–Scheinker syndrome (GSS)

Kuru• The name kuru translates to “shiver” or “trembling in fear.” Kuru has no

known cure and is generally fatal within one year.

• Kuru is an extremely rare and fatal nervous system disease. The disease started during the 1950s and 1960s among the people in New Guinea (world's second-largest island).

• Symptoms of the disease are difficulty walking, swallowing, and chewing. Symptoms also include loss of coordination and muscle twitching.

• Disease can be caused by eating an infected brain or coming into contact with open wounds or sores.

Kuru: Diagnosis and Treatment

• Can be confirmed by a neurological exam which is a comprehensive medical examination (medical history, neurological function, and blood tests).

• No treatment is available.

Fatal insomnia Has two forms:1. Familial: • Called as fatal familial insomnia.• Inherited. • Occurs due to a mutation in the gene for a normal protein called cellular

prion protein (PrPC).

2. Sporadic:• Occurs spontaneously, without a genetic mutation.• Differ from other prion diseases because they affect one area of the brain,

the thalamus, which influences sleep.• Causes After a person's 30s. • Symptoms: Patients will have minor difficulties falling asleep and

occasional muscle twitching, spasms, and stiffness. Eventually, they cannot sleep at all.

Fatal insomnia : Diagnosis and Treatment

• Can be confirmed by a genetic testing.

• No treatment is available.

Is the RefSeq mRNA record reviewed?

How many alternatively spliced products have been annotated for the gene

• Click on the Homologene link to obtain information about the Homologs from other eukaryotes.

• Change the Display option to "Alignment Scores". How great is the percent identity between the human and mouse proteins?

• View the alignment by clicking on the "Blast" link.

Homologs

1.P.Troglodytes (Common chimpanzee)

2.M.Mulatta (Rhesus macaque)

3.B.Taurus (Cattle)

4.M.Musculus (House mouse)

5.R.Norvegicus (Brown rat)

Go back to the Entrez Gene report.

i.Identify the clinically-associated variations annotated on this gene by clicking on the SNP link.

ii.Next, Select the “Clinical/LSDB” tab.

iii.How many of them are missense (nonsynonymous) changes?

iv.To determine whether known SNPs in the coding region of a gene are associated with any phenotype, access the OMIM record by clicking on the icon.

SNP - Single Nucleotide Polymorphism

• DNA sequence variation occurring within a population in which a Single Nucleotide — A, T, C or G — in the genome shared, differs between members of a biological species or paired chromosomes.

missense (nonsynonymous) changes

• This image shows an example of missense mutation. One of the nucleotides (adenine) is replaced by another nucleotide (cytosine) in the DNA sequence.

• This results in an incorrect amino acid (here, proline) being incorporated into the protein sequence.

Phenotype• In micro level,

– organism's actual observed properties, such as morphology, development, or behavior based on genes

• In Macro level– it determines the observerble nature of a living beingsuch as,

• appearence• behaviors• attitudes• personalty

Online Mendelian Inheritance in Man - OMIM

• A database that catalogues all the known diseases with a genetic component,

What is OMIM?• Online Mendelian Inheritance in Man (OMIM®) is a

continuously updated catalog of human genes and genetic disorders and traits, with particular focus on the molecular relationship between genetic variation and phenotypic expression. It is thus considered to be a phenotypic companion to the Human Genome Project. OMIM is a continuation of Dr. Victor A. McKusick's Mendelian Inheritance in Man, which was published through 12 editions, the last in 1998. OMIM is currently biocurated at the McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine

Continue of OMIMEach OMIM entry is given a unique six-digit number as summarized below:

• 1----- (100000- ) 2----- (200000- ) Autosomal loci or phenotypes (entries created before May 15, 1994)

• • 3----- (300000- ) X-linked loci or phenotypes• • 4----- (400000- ) Y-linked loci or phenotypes• • 5----- (500000- ) Mitochondrial loci or phenotypes• • 6----- (600000- ) Autosomal loci or phenotypes (entries created after May 15,

1994)

What is Allelic Variants?

• Allelic variants (mutations; see 1.4) are designated by the MIM number of the entry, followed by a decimal point and a unique 4-digit variant number. For example, allelic variants in the factor IX gene (300746) are numbered 300746.0001 through 300746.0101

Compare the missense changes from the SNP report with the "ALLELIC

VARIANTS" in the OMIM record• http://www.ncbi.nlm.nih.gov/gene/5621

Snp record viewhttp://www.ncbi.nlm.nih.gov/snp?LinkName=gene_snp&from_uid=5621