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.

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).

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.

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.

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

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.

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.

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.

Schematic representation

Recall process to construct proteins

If there is a change in the DNA…

SNPs with no change

SNPs with small changes

SNPs causing changes in shape

Some protein changes are eventual

But when they happen, they can lead to diseases

Another disease

Sickle-cell disease

Glu -> GTG

Val -> GAG

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.

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

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/

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.

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.

Árvores Filogenéticas

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.

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

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.

Phylogeny

Orangutan Gorilla Chimpanzee Human

From the Tree of the Life Website,University of Arizona

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

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.

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

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

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)