SNPs and CNPsBy: 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?• 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

1. Select genes known in a process

2. Examine the genes in people with and without a disease

3. 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

o What the variants areo Where the variants occur in our DNAo How they are distributed among populations

• Able to see how SNPs are organized on chromosomes • Construction of Hapmap occurs in three steps:

1. Single Nucleotide Polymorphisms 2. Adjacent SNPs inherited together compiled into

haplotypes 3. “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