The ABC's of DNA sequencing...(ish)

Want to hear a (anti) joke?   Ok, here goes: "Abby, Bob, and Carol walk into a hospital.......and get their DNA tested for a horrible disease." Because the hospital that they walked into a hospital stuck in the 1980's they are using the Sanger method of sequencing to examine the DNA. To make a complex process rather simple, the Sanger method takes a sample of DNA from a subject, each base (A,T,G, C) is radioactively labeled (for detection later in a sequencing machine) and synthesized (copied). The newly synthesized DNA is then put through gel electrophoresis, which uses electricity and gel to sort the DNA Molecules by size and creates a visual representation on X-Ray fil, or the gel itself. (Figure 1)

(Fig. 1)

So, Abby, Bob, and Carol all had their DNA run through the Sanger process. The next step to get their results was for a "skilled" technician to write out the DNA sequence out. To write out the sequence you start at the bottom and write down the the letter that each mark represents. (the above sequence would be CGA GAT ATA etc...) Each letter represents a base, and he three letter sorting is important later on to determine the proteins that the sequence represents.

Abby's Sequence went:  ATG GTG CAC CTG ACT CCT GTG GAG AAG TCT GCC

Bob's Sequence went:    ATG GTG CAC CTG ACT CCT GTG GAG TAG TCT GCC

Carol's Sequence went:  ATG GTG CAC CTG ACC CTG AGG AGA AGT CTG CCC

In order to determine if they had the "life ending disease" their DNA sequences were compared to that a control subject (Norm) who did not have the disease.

Norm's Sequence was:   ATG GTG CAC CTG ACT CCT GAG GAG AAG TCT GCC

To determine the likely hood of having the disease the hospital needs to create a quantitative representation of what all those letters mean, so the create a number called the percent similarity. To do this the put the number of bases that are simular to "Norms" over the total number of bases in the sequence. I took the liberty of putting the results into a pretty little graph to show how each of the patients compares to the control (Norm.).

As you can very clearly see, Bob and Abby have a very simular (96.45%) DNA sequence to the control, which would lead me to assume that they would not have the horrible disease. Carol on the other hand was not that simular to Norm, therefore I would assume that she has the disease. 

One Last Note: (for content stuffs) 

The reason that DNA is sequenced in chunks of three (called codons) because the proteins that are formed based on the DNA are created from the three letter sequences. Each set of three letters, in other words, represents a protein. To determine what proteins are made by what sequence, one has to look at a magical "decoder table." The nice thing about proteins and DNA sequences, is that the same protein can usually be made a number of different sequences, so long as the first and second letters of the sequence are the same. For example, the sequences CCU CCC CCA and CCG all make "pro" (Proline.) Which means that if a sequence is off, the proteins won't always be off. Which is the important part...

Eugenics. Post (3 Pages? Psh....)

So, this week (ok maybe six weeks ago) we started a project on Eugenics (which was a minor factor in the delay of my last blog post). Eugenics is "the applied science or biosocial movement which advocates the use of practices aimed at improving the genetic composition of a population," at least according to wikipedia. In much simpler terms it's all about controlling the population's genetic makeup in order to ensure a "perfect" population. So, Lets look at the essential questions of this rather unsavory "biological science":


What were the social origins of eugenics?
 Eugenics developed in the wake of economic and social problems following the civil war. Depressions occurred every decade from 1876 to the beginnings of the 20th century. These depressions fueled a labor unrest, caused by militant labor unions and the rapid growth of american industry. Social Darwinism had attempted to explain the inequalities experienced by the lower class as "survival of the fittest", but by the the beginning of th 20th century that idea had been flipped.  Those people who sat at the top of the economy in the upper class had a declining birthrate. Meaning that they were in fact losing the struggle for existence. Not only were the working  class working and organizing against them, but they were also out-reproducing them. To solve all the new problems that came with industrialization, a new philosophy called progressivism emerged. Progressivism was all about managed capitalism- letting the government and planning have an increased role in the market. The biggest component of this was the idea of scientific management: long-term planning by specially trained university experts. This new "managerial" class would soon become important to the managerial process, science was seen as the new "cure-all" that would bring in a new era of control to nature and human society. Suddenly, the the idea that genetics explained the underlined causes of human social problems (feeble-mindedness, alcoholism, etc...) came about. These issues were said to be caused by "the inheritance of defective germ plasm", believers argued that society paid a very high price by allowing those people (who would eventually be cared for by the state) to be born. Their solution? Sterilize that "defective" adult. By doing this, eugenicists claimed that future generations could save thousands of dollars. Another problem that eugenics solved was the mutual antipathy, shared by eugenicists and their wealthy supporters, towards militant labor unions and political revolution. Both of which were seen to be caused by the large influx of immigrants from southern Europe. Eugenicists then claimed to have data that showed the problem was in their genes, effectively placing the blame in "germ plasm" and ethnic groups, rather than in the structure of society its self. In essence, they managed to use science as an excuse to blame victims for their own problems. Basically, eugenics offered the prospect of a smooth transition to a better future, and a method to attack social problems at their roots.

What were the scientific origins of eugenics?
In 1883 Francis Galton coined the term eugenics as a moral philosophy to encourage the healthiest, and most able people to have more children. His version is known as "positive eugenics". Negative eugenics supported the removal of the weakest members from a population. Needless to say the negative version was favored more...The idea of segregating people deemed unfit to reproduce dates back to antiquity. Concerns about environmental influences that could damage heredity were formalized in the 1700's as "degeneracy theory". It would maintain a strong following up until the 19th century. Onanism was presented as the first cause of degeneracy in medical schools. This fear of degeneracy through onanism prompted prison doctor Henry Clay Sharp to carry out vasectomies on prisoners beginning in 1899, later resulting a law that would make it mandatory in Indiana. Benedict Morel's work extended the causes of degeneracy to include poisoning by toxic substances. Richard Dugale believed that  good environments could turn a degenerate into a worthy citizen through three generations. He conducted a study (The Jukes, 1877) to prove this. In the 1880's August Wiseman's theory on germ plasm managed to convince most people that changes to the body tissues (the soma) had no effect on the reproductive tissues (the germ plasm). So, naturally this theory was favored by negative eugenics. Go figure..  Most basic scientists would shun eugenics as vulgar, but their contributions to the field of genetics would be absorbed by eugenicists. Eventually, Mendelian analysis would be part of most eugenicists backgrounds, as would agriculture where most eugenicists were present [like the american breeders ass. (ABA)]. Evolutionary models would also contribute to eugenic theory, with fears that the smarter families would have less kids than the degenerate families due to welfare supporting these people, which upset the role of natural selection. Soon even medicine hopped on the bandwagon, with doctors advocating medicine and programs to deal with degenerates. Most would argue that sterilization was the best plan for dealing with degenerates. With vasectomies and tubal litigation as the preferred methods because they did not alter the physical or psychological contributions of reproductive organs as well as saving the state money by not having to institutionalize them.

What research methods were used to study eugenics and what were their flaws?
At the core of eugenics was the was a research effort to apply Mendel's laws to the inheritance of human traits. Eugenicists examined family pedigrees to determine the inheritance pattern of a trait, and then score family members for the presence or absence of that trait. They succeeded quite well on the first half, as large families were easy to spot patterns in, but scoring members was especially difficult due to the complexity of most traits. The main problem here was that researchers were lax in defining the traits they were studying. Most of the traits (mental and behavioral) they were looking for were subjective, so the diagnosis was often mishandled, corrupting their data. The second issue with their research was that they often treated large complex issues as if they were caused by one thing, and not multiple variables combining into one issue. Data was also affected by poor survey and statistical methods. Most researchers got their information from second had sources and heresy, due to to a lack of good medical records. Also, when presenting results, eugenicists were VERY biased, using their data to falsely exaggerate claims. False quantification also plagued researchers. For example IQ tests that were dependent on cultural knowledge were given to immigrants under a wide variety of conditions, and were counted as official evidence that immigrants were feeble minded.  To simplify it all, the research that was done was biased, not properly administrated, and to many variables were left open.

How did eugenics research impact American society?
Eugenics had a very large negative impact on American society. In a period of changing times, marked by industrial revolutions, and an influx of immigration. Eugenics promoted racial in equality, social inequality, and a sense of hatred against the lower class in America. Numerous rights of people were violated with the passing of marriage laws (preventing people from marrying outside their race), sterilization laws (forcibly sterilizing those with "bad" germ plasm), and the immigration restriction that would result from studies showing that they were bad for the population. The affects of American eugenics could also be felt across the world, with German leaders (on trial for war crimes Nuremberg) citing American eugenicists as the inspiration behind Hitlers purification laws, and the eventual genocide of the Holocaust.

DNA-My Model, and an gentle explanation

Recently in Biology we have been working on a rather fun concept: DeoxyRibonucleic Acid otherwise known as DNA. So, I made a model of it on Google Docs (*cough* tech savvy 4 *cough*) in order to study for the DNA quiz last week.  So here goes my explanation of DNA's structure, and what it all means...

Double Helix (Fig. 1)

At the base of DNA are little cornerstones known as nucleotides. A nucleotide is made up of three pieces a phosphate (the white circle), a five carbon sugar (deoxyribose, the black pentagon) and a nitrogenous base (one of the colorful weird pieces in the middle). Nucleotides first join together by connecting together the front pieces sugar with the second pieces phosphate creating a single chain. The second place that nucleotides link together, to create a double chain (Kiel's brand new descriptive word of the day) is in the middle linking two nitrogenous bases together. The only condition with nitrogenous bases connecting together is that A (Adenine) bases can only link with T (Thymine) bases and C (Cytosine) bases must link with G (Guanine) bases. It is that pattern of bases (read three at a time) that are the genetic instructions used in the development functioning of all living organisms. The flat structure shown above, in real life, is twisted into a double helix (fig. 1) and get wrapped around a protein in the cell (but, thats way above the scope of this post). (fig. 2).

DNA wrapped around a DNA-Binding Protein (Fig. 2)