Documente Academic
Documente Profesional
Documente Cultură
By
Ayman Elsamanoudy
Definition of Genotype This is the "internally coded, inheritable information" carried by all living organisms. This stored information is used as a set of instructions for building and maintaining a living creature. These instructions are found within almost all cells (the "internal" part), they are written in a coded language (the genetic code), they are copied at the time of cell division or reproduction and are passed from one generation to the next ("inheritable"). These instructions are intimately involved with all aspects of the life of a cell or an organism. They control everything from the formation of protein macromolecules, to the regulation of metabolism and synthesis.
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Definition of phenotype
This is the "outward, physical manifestation" of the organism. These are the physical parts, the sum of the atoms, molecules, macromolecules, cells, structures, metabolism, energy utilization, tissues, organs, reflexes and behaviors;>>>>>>anything that is part of the observable structure, function or behavior of a living organism.
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environmental factors
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G E interaction
Environment
Health outcome o r
A trait is a distinct variant of a phenotypic character of an organism that may be inherited, environmentally determined or somewhere in between. For example: eye color: It is the character, which may be blue, brown and hazel >>>>> called traits.
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Genetic code
It is the stored information on one of the two strands of a DNA molecules as a linear, non-overlapping sequence of the nitrogenous bases Adenine (A), Guanine (G), Cytosine (C) and Thymine (T). The genetic code consists of a sequence of three letter "words" (sometimes called 'triplets', sometimes called 'codons'), written one after another along the length of the DNA strand. Each code word is a unique combination of three letters that will eventually be interpreted as a single amino acid in a polypeptide chain. There are 64 code words possible from an 'alphabet' of four letters. One of these code words, the 'start signal' begins all the sequences that code for amino acid chains(AUG). Three of these code words act as 'stop signals' that indicate that the message is over(UGA ,UAG,UAA). 8 All the other sequences code for specific amino acids.
Definition of An allele : It is an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome. These DNA codings determine specific traits that can be passed on from parents to offspring. The process by which alleles are transmitted was discovered by Gregor Mendel and formulated in what is known as Mendel's law of segregation. Sometimes, different alleles can result in different traits, such as color. Or, different alleles will have the same result in the expression of a gene. Most multicellular organisms have two sets of chromosomes (Diploid). Each chromosome has one gene and one allele). If both alleles are the same, they are homozygotes If the 10 alleles are different, they are heterozygotes.
Mutations are permenat changes of base sequence of nucleotides in the genetic code of the DNA genome . Polymorphism: Variation in DNA sequence of allele gene from one individual to another that is common in population ( mostly not associated with impaired protein structure).
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Mutation may be : 1- Germinal mutation :occur in the germ cells and can be passed to the future generation . 2-Somatic mutation :occur in somatic cells and cannot be transmitted to offspring.
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Mutations are changes the DNA sequence of a cell's genome. Effect on structure: I. Small scale: 1. Point mutations exchange a single nucleotide for another. Transition that exchanges a purine for a purine (A G) or a pyrimidine for a pyrimidine, (C T) .OR Tranversion which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T A/G). Effcts : 1. Silent mutations: which code for the same amino acid. 2. Mis-sense mutations: which code for a different amino acid. 3. Non-sense mutations: which code for a stop and can truncate the protein.
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2.
Insertions add one or more extra nucleotides into the DNA. 3. Deletions remove one or more nucleotides from the DNA. Both insertions &deletion alter the reading frame of the gene. So,both of which can significantly alter the gene product. II. Large-scale mutations in chromosomal structure, including: Deletion, translocation.
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Effect on protein sequence: 1. A frame shift mutation is a mutation caused by insertion or deletion. 2. A nonsense mutation:is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and possibly a truncated, and often nonfunctional protein product. 3. Mis-sense mutations:are types of point mutation where a single nucleotide is changed to cause substitution of a different amino acid. This in turn can render the resulting protein nonfunctional. 4. A neutral mutation :is a mutation that occurs in an amino acid codon which results in the use of a different, but chemically similar, amino acid (arginine by lysine) 5. Silent mutations : are mutations that do not result in a change to the amino acid sequence of a protein.
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Promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are located near the genes they regulate, on the same strand and typically upstream (towards the 5 region of the sense strand). Enhancer is a short region of DNA that can be bound with proteins (transcription factors) to enhance transcription levels of genes (hence the name).
Gene Enhancer SNPs 1
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Gene
Enhancer SNPs 1 2 factor 3 4 that5 Transcription is a protein binds to specific DNA sequence, controlling the transcription of genetic information from DNA to mRNA. Promoter Start Exon Intro n Exon Termination
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SNPs
Most of the population At least 1 percent of the population
G to C
Common sequence
Variant sequence
SNP site
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SNP genotype
We inherit two copies of each chromosome (one from each parent) For a given SNP the genotype defines the type of alleles we carry Example: for the SNP A/G ones genotype may be:
AA if both copies of the chromosome have A GG if both copies of the chromosome have G AG or GA if one copy has A and the other has G The first two cases are called homozygous and latter two are heterozygous
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Types of SNPs
Noncoding SNPs 5 UTR 3 UTR Introns Intergenic Regions Regulatory Splicing Transcriptional regulation (promoter & TF binding sites) Translational regulation (initiation or termination) Coding SNPs Synonymous SNPs (third position variation) Replacement SNPs (change Amino acid) Functional SNPs (acceptable amino acid replacement) Non-functional SNPs (traits & diseases)
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SNP1. This SNP could affect the binding of transcription factors to the enhancer and thus the expression of the gene. !!! !!! SNP2. This SNP lies in a non-functional region and will probably have no effect. It could affect histone binding. !!! !!! SNP3. This SNP could affect the binding of the transcriptional machinery (esp. RNA polymerase II) to the promoter !!! !!! SNP4. This SNP is in an exon and will code an amino acid. However, it will only have an effect if the change triplet will encode a different amino acid (e.g. AGA and AGG both encode arginine). SNP5. This SNP will be spliced out and therefore it will not have an effect. !!! !!!
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DNA SNP A to C
CTC
mRNA
GAU
GAG
Aspartic acid
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DNA SNP T to A
C A A
mRNA
SNPs can alter the function of the protein 1. Directly : alter an amino acid sequence
GAU
GUU
Aspartic acid
Valine
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Change in shape
Nomenclature
Nucleotide substitution (e.g. 76A>T) The number is the position of the nucleotide from the 5' end. The first letter represents the wild type nucleotide The second letter represents the nucleotide which replaced the wild type. So, the adenine at the 76th position was replaced by a thymine.
If it becomes necessary to differentiate between mutations in genomic DNA, mitochondrial DNA, and RNA, a simple convention is used. g.100G>C if the mutation occurred in genomic DNA, m.100G>C if the mutation occurred in mitochondrial, r.100g>c if the mutation occurred in RNA. Note that for mutations in RNA, the nucleotide code is written in lower case.
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Nomenclature
Amino acid substitution (e.g. D111E) The first letter is the one letter code of the wild type amino acid The number is the position of the amino acid from the N terminus The second letter is the one letter code of the amino acid present in the mutation. Nonsense mutations are represented with an X for the second amino acid (e.g. D111X). Amino acid deletion (e.g. F508) The Greek letter (delta) indicates a deletion. The letter refers to the amino acid present in the wild type The number is the position from the N terminus of the amino acid were it to be present as in the wild type.
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Nomenclature
There is no nucleotide 0 Nucleotide 1 is the A of the ATG-translation initiation codon The nucleotide 5' of the ATG-translation initiation codon is -1, the previous 2,etc. The nucleotide 3' of the translation stop codon is *1, the next *2, etc. Beginning of the intron: the number of the last nucleotide of the previous exon, a plus sign and the position in the intron, like c.77+1G, c.77+2T, etc. End of the intron; the number of the first nucleotide of the following exon, a minus 32 sign and the position upstream in the intron, like c.78-1G.
= Variations in DNA that cause latent effects Many years later Many years later
Disease predisposition: The Genetic differences between human populations 34 make one population more susceptible to particular disease.
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understanding why individuals differ in their abilities to absorb or clear certain drugs. determining why an individual may experience an adverse side effect to a particular drug (i.e Adverse Drug reaction).
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