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.

Make up about 90% of all human genetic variation. 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.

A SNP might change the DNA sequence 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, but scientists believe others could predispose people to disease or influence their response to a drug.

SNPs have various functions G/T promoter G/T G/C GU AG TFBS 5’UTR atggacgtactggtg tctgagtgctccgcg 3’UTR A/G G/T Type 1 transcript Transcrip. Factor Binding Sites Type 2 transcript Type 3 transcript Altering the encoded protein Alternative splicing Premature termination Transcription regulation Type 1 protein M D V L V S E C S A M D V L V S E S S A Type 2 protein Type 3 protein

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-W644 doi: http://nar.oxfordjournals.org/cgi/content/full/34/suppl_2/W642 SNP@Domain Site: http://snpnavigator.net/

dbSNP: the NCBI database of genetic variation Sherry 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. Ilyin Structure SNP (StSNP): a web server for mapping and modeling nsSNPs on protein structures with linkage to metabolic pathways NAR, July 13, 2007; 35(suppl_2): W384 - W392. J. Park, S. Hwang, Y. S. Lee, S.-C. Kim, and D. Lee SNP@Ethnos: a database of ethnically variant single-nucleotide polymorphisms NAR, 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 Filogenéticas São 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 Orangutan Gorilla Chimpanzee Human

A Árvore da Vida da SCIENCE A revista Science tem uma Árvore da Vida on-line: http://www.sciencemag.org/feature/data/tol/

Evolução Convergente e Divergente Evolução é dita convergente quando organismos que não são fortemente relacionados desenvolvem características similares de forma independente. Ex: Asas de insetos, aves e morcego. Evolução é dita divergente quando organismos que são fortemente relacionados desenvolvem características diferentes.

Terminologia 1 1 1 1 1 1 1 1 1 1 1 no homoplasy back-mutation 1 1 1 1 1 1 1 1 1 1 1 no homoplasy back-mutation parallel evolution

Filogenia Perfeita 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.

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)