single nucleotide polymorphisms (snps)

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Single Nucleotide Polymorphisms (SNPs)

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Single Nucleotide Polymorphisms (SNPs). DNA fragment. Nitrogenous bases: A, T, G e C. In a eukaryotic cell, the DNA is localized inside of the nucleus, compacted and organized in a structure called cromosome. - PowerPoint PPT Presentation

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Page 1: Single Nucleotide Polymorphisms (SNPs)

Single Nucleotide Polymorphisms (SNPs)

Page 2: Single Nucleotide Polymorphisms (SNPs)

DNA fragment

Nitrogenous bases: A, T, G e C.

In a eukaryotic cell, the DNA is localized inside of the nucleus, compacted and organized in a structure called cromosome.

Page 3: Single Nucleotide Polymorphisms (SNPs)

Chromosome and Genotype

In diploid species, like humans, having 2n pairs of chromosome, where n is the number of differentes chromosomes.

The genotype is the set of all chromosomes. (in humans are 46).

Page 4: Single Nucleotide Polymorphisms (SNPs)

Haplotype

In haplotypes species, have n chromosomes, only one copy.

In humans the genotype is the set of 23 chromosomes from the father and another 23 from the mother.

Page 5: Single Nucleotide Polymorphisms (SNPs)

Evolution

These chromosomes are passed with very great fidelity from one generation to the next. However, occasionally a mutation has occurred and effectively changed one base to another.

The variation occurred in genetics sequences are many types, but the main are mutations and polymorphisms.

Page 6: Single Nucleotide Polymorphisms (SNPs)

Polymorphism

When several chromosomes from a population are compared, a site where a mutation occurred in the past may be found, and some chromosomes will have the original base and others will have the new base, i.e. the population will be polymorphic.

The variation of DNA sequences inside of the same species and have at least two types, is called alleles.

Traça (Biston betularia) branca

Variante preta da traça

Page 7: Single Nucleotide Polymorphisms (SNPs)

Polymorphism

A special kind of polymorphism is the target of many researchs, because of the major variation frequence in DNA humans.

This kind of ploymorphism is called: Single Nucleotideo Polymorphism ou SNP.

Page 8: Single Nucleotide Polymorphisms (SNPs)

What are SNPs ?(Single Nucleotide Polymorphisms)

Common DNA sequence variations among individuals in genome wherein the least frequent allele has an abundance of 1% or greater.

Make up about 90% of all human genetic variation.

Some SNPs are reported to be highly related to diseases or influence cells response to a drug.

Page 9: Single Nucleotide Polymorphisms (SNPs)

What are SNPs?

SNPs are DNA sequence variations that occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered.

Example: A SNP might change the DNA sequence

AAGGCTAA to ATGGCTAA.

For a variation to be considered a SNP it must occur in at least 1% of the population.

SNPs make up about 90% of all human genetic variation.

Page 10: Single Nucleotide Polymorphisms (SNPs)

Schematic representation

Page 11: Single Nucleotide Polymorphisms (SNPs)

Recall process to construct proteins

Page 12: Single Nucleotide Polymorphisms (SNPs)

If there is a change in the DNA…

Page 13: Single Nucleotide Polymorphisms (SNPs)

SNPs with no change

Page 14: Single Nucleotide Polymorphisms (SNPs)

SNPs with small changes

Page 15: Single Nucleotide Polymorphisms (SNPs)

SNPs causing changes in shape

Page 16: Single Nucleotide Polymorphisms (SNPs)

Some protein changes are eventual

Page 17: Single Nucleotide Polymorphisms (SNPs)

But when they happen, they can lead to diseases

Page 18: Single Nucleotide Polymorphisms (SNPs)

Another disease

Sickle-cell disease

Glu -> GTG

Val -> GAG

Page 19: Single Nucleotide Polymorphisms (SNPs)
Page 20: Single Nucleotide Polymorphisms (SNPs)

What are SNPs?

SNPs occur every 100 to 300 bases along the 3-billion-base human genome.

Two of every three SNPs involve the replacement of cytosine (C) with thymine (T).

SNPs can occur in both coding (gene) and noncoding regions of the genome.

Many SNPs have no effect on cell function, butscientists believe others could predispose people to disease or influence their response to a drug.

Page 21: Single Nucleotide Polymorphisms (SNPs)

atggacgtactggtg

5’UTRTFBS

promoter

tctgagtgctccgcg

GU AG3’UTR

Type 1 transcript

M D V L V S E C S AType 1 protein

M D V L V S E S S AType 2 protein

1. Altering the encoded protein

2. Alternative splicing

3. Premature termination

4. Transcription regulation

Type 2 transcript

Type 3 protein

Type 3 transcript

G/CG/TG/T

G/TA/G

Transcrip. Factor Binding Sites

SNPs have various functions

Page 22: Single Nucleotide Polymorphisms (SNPs)

Important SNP Resource

SNP@Domain: a web resource of single nucleotide polymorphisms (SNPs) within protein domain structures and sequences

Areum Han, Hyo Jin Kang, Yoobok Cho, Sunghoon Lee, Young Joo Kim and Sungsam Gong

NAR 2006 34(Web Server issue):W642-W644doi: http://nar.oxfordjournals.org/cgi/content/full/34/suppl_2/W642

SNP@Domain Site: http://snpnavigator.net/

Page 23: Single Nucleotide Polymorphisms (SNPs)

dbSNP: the NCBI database of genetic variationSherry ST, Ward MH, Kholodov M, Baker J, Phan L,

Smigielski EM, Sirotkin K.Nucleic Acids Research (NAR) 2001; 29:308-311.

Page 24: Single Nucleotide Polymorphisms (SNPs)

Recent SNPs Sites and BDs

Uzun, C. M. Leslin, A. Abyzov, and V. IlyinStructure SNP (StSNP): a web server for mapping and modeling nsSNPs on protein structures with linkage to metabolic pathwaysNAR, July 13, 2007; 35(suppl_2): W384 - W392.

J. Park, S. Hwang, Y. S. Lee, S.-C. Kim, and D. LeeSNP@Ethnos: a database of ethnically variant single-nucleotide polymorphismsNAR, January 12, 2007; 35(suppl_1): D711 - D715.

Page 25: Single Nucleotide Polymorphisms (SNPs)

Árvores Filogenéticas

Page 26: Single Nucleotide Polymorphisms (SNPs)

Árvores Filogenéticas

Árvores filogenéticas são árvores que representam as relações evolucionárias entre as diferentes espécies.

Cada nó com descendentes é considerado o ancestral comum mais recente destes descendentes.

Muitas vezes o comprimento das arestas representa a distância em tempo de evolução.

Há várias formas de representação.

Page 27: Single Nucleotide Polymorphisms (SNPs)
Page 28: Single Nucleotide Polymorphisms (SNPs)

Árvore Filogenética

Phylogenetic tree showing the relationship between the archaea and other forms of life. Eukaryotes are colored red, archaea green and bacteria blue. Adapted from Ciccarelli et al. 2006

Page 29: Single Nucleotide Polymorphisms (SNPs)

Árvores FilogenéticasSão construídas - Com base em distâncias (diferenças) entre seqüências de DNA das espécies envolvidas. - Sob a hipótese de que todas evoluíram de um ancestral comum.

Muitas vezes são representadas através de dendogramas.

Page 30: Single Nucleotide Polymorphisms (SNPs)

Phylogeny

Orangutan Gorilla Chimpanzee Human

From the Tree of the Life Website,University of Arizona

Page 31: Single Nucleotide Polymorphisms (SNPs)

A Árvore da Vida da SCIENCE

A revista Science tem uma Árvore da Vida on-line:

ttp:::www:s m :oh cie ce ag

r : tur : t: : tol:gfeae daa

Page 32: Single Nucleotide Polymorphisms (SNPs)

Evolução Convergente e Divergente

Evolução é dita convergenteconvergente quando organismos que não são fortemente relacionados desenvolvem características similares de forma independente.

Ex: Asas de insetos, aves e morcego.

Evolução é dita divergentedivergente quando organismos que são fortemente relacionados desenvolvem características diferentes.

Page 33: Single Nucleotide Polymorphisms (SNPs)

0 0 1 1

0

0

0

0 1 1 0 0

0

1

1

0 1 0 0 1

0

1

0

1

1 0 0

no homoplasy back-mutation parallel evolution

Terminologia

Page 34: Single Nucleotide Polymorphisms (SNPs)

Um conjunto de seqüências S tem uma filogenia perfeita se existe uma árvore filogenética sobre S tal que:

- Cada estado de cada caracter ocupa uma sub-árvore, ou

- Nenhum caracter tem back-mutation ou evolução paralela.

Filogenia Perfeita

Page 35: Single Nucleotide Polymorphisms (SNPs)

Exemplo A=(0,0), B=(0,1), C=(1,0), D=(1,1)

não tem uma filogenia perfeita.

Intuitivamente,

- O 1o. elemento associa (A, B) e (C,D)

- O 2o. elemento associa (A, C) e (B, D)