SNPs and CNPs By: David Wendel

What are SNPs? (“snips”) Single Nucleotide Polymorphisms or (SNV) Occurs when one nucleotide is altered in a genome Four versions- one for each nucleotide Similar to mutations Two or more versions of a sequence must each be present in at least one percent of the general population

What are SNPs? (cont.) Many have no effect on cell function Do not directly cause disease Most found outside of protein sequences Likely to alter protein functions if inside Help pinpoint disease on human genome map Evolutionarily stable

What are CNPs (“cnips”) Copy Number Polymorphisms or (CNV) Alterations in DNA Affect sections of DNA Different number of copies of sections Thousands to millions Occurs in over 1% of population - polymorphism Considered normal variations

SNPs and CNPs in Humans Human DNA is very similar 99.6% of human DNA is identical to all other humans Other 0.4% is made up of CNPs and SNPs SNPs- 80% of the 0.4% Small scale variant CNPs- 20% of the 0.4% Large scale variant

How do we find SNPs? Genomic Approaches Functional Approaches Two main ways scientists identify, categorize, and catalog SNPs Genomic Approaches Functional Approaches Primer Extension is also used

Genomic Approaches Scientists who want to see the big picture Hundreds of scientists involved Genomes of numerous individuals are compared Computer-powered data analysis Results available to anyone on internet

Functional Approaches Scientists interested in particular diseases or drug responses Select genes known in a process Examine the genes in people with and without a disease Identify SNPs that correspond with particular response

Primer Extension Less expensive Alternative method

Haplotypes A set of single nucleotide polymorphisms Set is on a single chromosome of a chromosome pair that is statistically associated Associations can identify other polymorphic sites in the region SNPs close together on the chromosome Valuable for investigating genetics behind diseases

HAPMAP (Haplotype Map)

HAPMAP (Haplotype Map) cont. Hapmap- a catalog of common genetic variants that occur in human beings What the variants are Where the variants occur in our DNA How they are distributed among populations Able to see how SNPs are organized on chromosomes Construction of Hapmap occurs in three steps: Single Nucleotide Polymorphisms Adjacent SNPs inherited together compiled into haplotypes “Tag” SNPs in haplotypes identified that uniquely identify those haplotypes.

Hapmap I 2005 This was the first phase of the project The project was launched in October 2002 Original goal to be finished was September 2005 Finished first draft in February 2005 Contained 1,000,000 most common SNPs

Hapmap II 2006 Results from Phase II were released in August 2006 These results were published in February 2007 10,000,000 SNPs were included in this Hapmap

Hapmap III 2010 The third phase was published in 2010 Data from 1,184 individuals 11 global populations 1,410,616 SNPs were released for detailed studies Ten 100-kilobase ENCODE regions were sequenced in 692 of these individuals Allowed integration of SNPs and CNPs

Average Person and SNPs Density of SNPs per base pair varies with every person SNPs occur about one in every 500- 1000 base pairs About 3,750,000 total