Wednesday, January 11, 2012

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I thought pedigree was for dogs…
            Genetic pedigrees are used to trace a family’s genetic history. This allows people to deduce most- if not all- of their ancestors’ genotypes for particular traits based on; those who expressed the trait in their phenotype, those who did not, and whether or not their children expressed the trait as well.


How it works:
Knowing that a person who expressed a recessive trait (rr) married someone who didn’t express that trait (R?) and had a child who also expressed the recessive trait (rr) you can figure out that the father must have been heterozygous (Rr) or their child could not have been homozygous recessive.
                                                                                                   What else do Pedigrees do?
            Using family pedigrees spouses can find the probabilities of their children getting a certain trait. A pedigree doubles as a family tree which is great for looking at one’s ancestry. A drawback to pedigrees is that it can be impossible to know a person’s genotype if there isn’t enough information to know for sure. Pedigrees do however give insight to whether or not a disorder is recessive or dominant based on the  inheritance patterns shown throughout a family's history.




http://www.uic.edu/classes/bms/bms655/gfx/pedigree1.gif





                                           What’s New?
Modern tools used for DNA and RNA processing (described below) serve a different function than pedigrees. These tools allow scientists to discover the specific genes that are actually causing the disorder; thus making it possible to make treatments specific to the genes that are causing the problem. These modern tools however are more expensive than pedigree analysis.DNA and RNA processing show you the genes where problems are arising, and using these tools scientists can find cures to cancers and disorders. Both pedigrees and modern tools show genotypes, but only modern tools can show what every gene’s role is.

Introduction to DNA and RNA analysis
     DNA and RNA analysis can be used to test groups of people with a disorder or cancer to see if they have certain mutated genes in common.  Pin pointing these genes can open the doors to treatments that can cure or slow down the disorder.
                                                                                What’s the difference?
http://3.bp.blogspot.com/
Using the analogy of a car; DNA analysis allows you to put your ear up against its hood to hear what is happening in the engine, and RNA processing is like opening the hood and being able to see the engine itself.

A bit on DNA analysis
Using DNA processing one can know the location of genes that cause disorders based on mutated genes people with the disorder have in common. A person has 3 billion bases from their mother, and three billion bases from their father. 99.9% of these bases are the same, and where these letters don't match up, there lies a mutation. A mutation only arises about one letter every 1000 nucleotide bases (this is called single nucleotide polymorphism), and most of the time mutations occur in DNA that doesn't code for anything (only about 1.5% of DNA actually codes for proteins). DNA analysis is looking at the tiny base changes someone has and comparing that information with other people with the same disorder in order to find out which gene is mutated.

DNA analysis in use
For instance, on the X chromosome there is a particular DNA polymorphism with two sites of spelling differences that differ in thymine and cytosine. These sites happen to lie on the gene that codes for a particular protein called apolipoprotein e on chromosome 19.There are three different spellings that these two sites can have: CC, CT, and TC. If you happen to be homozygous for the CC spelling (meaning that both the chromosome from your mom and dad have this alternate spelling) then you have a 60 or 70% lifetime risk of contracting Alzheimer's disease.  About 3% of people are homozygous for the CC spelling. Using DNA analysis you could find out whether or not you have that spelling. Knowing that the apolipoprotein e is part of the biological process that causes Alzheimer’s, scientists are making drugs that can slow down the production of that protein which in turn will delay Alzheimer's disease from your 60's to 70's into your 120's and 130's.
RNA analysis
       As DNA analysis is used to locate genes that cause disorders, RNA analysis is used to look at what every gene’s specific job is (looking under the hood of the car). Before RNA analysis was possible, scientists looked at multiple patients' leukemia under a microscope and concluded that only one type of leukemia existed. This didn't explain how some people did better on the medications than others. As new technology arose (enzyme testing, cytology, etc.), more evidence proved that there were indeed two different types of leukemia. It took 40 years for scientists to declare that there were two kinds. Today they are called AML and ALL, and they both have different treatments. Scientists needed a faster and more efficient way of figuring this out so they could discover more cancers that have multiple types and be able to treat them with medications specific to their type. Using DNA microarrays scientists can pop open the hood of the car and monitor every gene and its function instead of just guessing.
So how do they do that?
http://www.columbia.edu/~bo8/undergraduate_research/projects/sahil_mehta_project/images/cDNA-array.jpg
 
                                                          As if it wasn't complicated enough...

          These DNA microarray chips consist of a little sliver of glass on which there are little squares where 25 letter DNA sequences can be washed onto. To get the DNA sequences on the chip they have a mask that covers all of the squares except the ones you want to add a sequence to and they shine a light on it. This makes the surface unprotected and makes it possible to wash on the DNA sequence. Then you protect the surface and do the same to different squares and wash DNA sequences on them until you have the DNA sequence you want in each spot.

                                                                       What can you do whith that?
        
        The first spot could possibly have the complementary strand to the first gene in the human genome, and the second spot the second gene and so on. These would then be detectors to certain genes. After you could take some RNA from a tumor and inject it into the chip. Each sequence of RNA will find its detector or complementary strand of DNA that was laid out before. Then a scanner on the chip will detect how much each gene is turned on and off based on the intensity of that particular spot.

              This information allows you to look at a tumor and find out which genes are turned on in a group of test subjects who have a disorder, and therefore which genes are responsible for that cancer or disorder. Back to Leukemia, the ALL tumors have some specific genes that are turned on, and the AML tumors will have different genes turned on. These differences clearly show a distinction between the two types of Leukemia. Using these gene chips and the computer program that can classify the types of leukemia based on genes that are turned on and off, the ALL type of leukemia was further classified. It was discovered that there are 3 types of leukemia: ALL1, ALL2, and AML. Using RNA analysis like this, scientists can make a molecular taxonomy of all the tumors and how they can be split into different types and how they differ and are the same to each other.