Lecture, chapter 13 - Cloning and recombinant DNA

A cartoon version of how to ligate DNA into
plasmids as part of the cloning process
click image to see a full size pic
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Today we started covering chapter 13, an introduction to cloning and recombinant DNA technology. We have temporarily skipped the second half of the chapter on mutation, but we will get back to it after finishing the current chapter.

We talked about the definition of cloning, and the basic steps for cloning DNA, including the use of plasmids, YACs, and BACs. We also briefly reviewed the basics of constructing a genomic library and how to probe it when searching for a specific fragment of DNA.

On Thursday: We will talk about in vitro cloning (PCR), southern blots, and automated DNA sequencing.

Tomorrow: Bioethics debates...!!!

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Exam 02

Today we had our second midterm exam, covering materials from chapter 8 (DNA structure and chromosomal organization) to the beginning of chapter 11 (mutation - [mutation rate]).

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Lecture, chapter 11 - Mutation (causes of mutation)

Continuing with the chapter on mutation, today we talked about the main agents that act as mutagens, mainly radiation and chemicals. We discussed some of the different kinds of mutation and how mutagens promote them; also how different categories of chemicals interact with DNA witht he result of causing mutations.

Reminder: Exam 2 is tomorrow!

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Lecture, chapter 11 - Mutation

Today we started chapter 11, on mutation, the source of genetic variation.

We talked about the kind of mutations we are going to be focusing on (those that alter the nucleotidic sequence of genes), and how it is detected in humans when they are reflected in the phenotype.
We also discussed what the rate of mutation is, and how it is calculated in humans, based on the observed number mutant phenotypes in a set of births.

After lecturing we did a quick and dirty overview of a couple of execises in the Drosophila gene mapping lab. A handout in pdf format has been uploaded to both, the p-drive and the WebCT site for the class explaining how to do a three-point testcross.

Note: A three-point testcross exercise will be included in the exam this Friday.

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Lecture, chapter 10 - From proteins to phenotypes: Pharmacogenetics

Today we finished chapter 10, from proteins to genotypes. Specifically we talked about pharmacogenetics

There are phenotypes that become obvious only when people are exposed to chemicals. Whether they are drugs, chemicals in the environment, or chemicals in products we consume (food, clothing, etc.), different allele combinations make us more or less sensitive to exposure.

We talket about the first pharmcogenetic trait, discoverd in the 1930s, the ability or inability to taste PTC. This trait is trivial, but it has implications that have lead research that may find connections between sensitivity to certain tastes, diet, and obesity.
We also talkes about how between 100 and 1000 cel membrane proteins dictate our ability to smell or not smell certain chemicals. So many enzymes, most of which most likely have several alleles, and so many possible allele combinations make us virtually unique in our olfactory capacity.

In terms of sensitivity to chemicals in the environment, especially pesticides, it is ecogenetics the subfield that deals wit our genetic-based differences in sensitivity. Research is being done in many populations to determine safe levels of exposure to different chemicals. Such research involves an important genetic component.

On Monday: We will start chapter 11, on mutation as the source of genetc variation.

Reminder: Next Friday, May 01, we will have our second exam. over chapters 8, 9, 10, and 11, plus elements of our genetic mapping labs (both in human and Drosophila). Bring a calculator!

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Lecture, chapter 10 - From proteins to phenotypes

Today we covered most of chapter 10, from proteins to genotypes.

We talked about how mutations in genes that encode for transport proteins can be reflected in the phenotype. Our main example was hemoglobin. Mutations in the genes thay encode for any of the subunits of the protein can cause a variety of genetic disorders (hemoglobin variants, thalassemias) which most common symptom is anemia.

One of the better known cases is sickle cell anemia, caused by a mutation in the beta globins of hemoglobin, causing them to come become insoluble, resulting in the aggregation of the protein, therefore altering the shape of red blood cells and making them brittle.

Tomorrow: We'll finish chapter 10, covering the section on pharmacogenetics.

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Lab 07 - Human gene mapping

In Drosophila it is easy to find out how linked genes are since that can be determined by doing experimental crosses and measuring phenotypic frequencies in the offspring (see lab 06). In addition to that, we know what genes are found in specific chromosomes (fruit flies have only four pairs of chromosomes).
But in humans it is not that straight forward. Experimental crosses are out of the question, and humans tend to have very few progeny (even large families have very few offspring compared with the potentially thousands of offspring of a couple of fruit flies).

In humans, we have to rely on pedigrees. In this lab we considered three different pedigrees showing linkage between a genetic disorder and another trait. Students learned and practiced how to identify parental and recombinant types in the offpring of each generation, and in the third exercise calculated the odds ratio to determine linkage of traits.

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Lecture, chapters 9 and 10 - From genes to proteins, and from proteins to phenotypes

Today we finished chapter 9, on how genetic information is used to synthesize proteins, and started chapter 10, on how proteins are, or influence, the phenotype.

We talked about the possibilities of changing a polypeptide after it has been synthesized, thus accounting fopr the more than 100,000 enzymes in the human organism, which has just about 25,000 genes in its genome. We defined the difference between a polypeptide and a protein (hint: every protein is a polypeptide or a group of polypeptides, but not every polypeptide is a protein).
Then we talked about the levels of structure that proteins can have: Primary, secondary, tertiary, and, in some cases, quaternary. We finished the chapter by discussing some of the consequences of a mutation that alters the amino acid sequence of a protein.

We also started chapter 10, and discussed how certain mutations in the sequence of amino acids of enzymes and receptor proteins affect the phenotype of the person who bearing them.

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Lecture, chapter 9 - From genes to proteins

Today we continued covering chapter 9, on how the information stored in the genetic code gets reflected on a phenotype, specifically in proteins.

We talked about the processes of translation transcription, including the stages that each one has (initiation, elongation, and termination in both cases).

In the case of trascription we talked about the elements that are found in a gene, and how they get trnascribed into a pre-mRNA transcript, which gets modified into a mature mRNA transcript. We also discussed the different elements that make a mRNA molecule, including a 5' cap and a Poly-A tail.

In the case of translation we covered the cytoplasmatic elements that play a role in it: amino acids, ribosomes, and tRNA. We also discussed the chemical make up of amino acids, an amino, a carboxyl, and an 'R' groups, and a few of their characeristics.

On Monday: We'll finish chapter 9 and begin chapter 10.

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Lecture, chapters 8 and 9 - RNA, chromosome structure, and gene expression

Today we finished the chapter on DNA and chromosome structure. It should have been "nucleic acid and chromosome structure".

We discussed the primary and secondary structure of RNA, how DNA is coiled (and supercoiled) to from chromosomes, and then we started the next chapter in the text book, on how the information stored in DNA is used to form proteins.

Note: The draft papers on bioethical issues were returned with recommendations to improve what you have so far. Tomorrow I'll provide a handout with indications of how to cite and reference papers in a scientific fashion.

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Lab 06 - Mapping genes in Drosophila

http://www.drosophilab.com
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Although the actual lab will be a take-home lab, we set the stage to do the work we need to do in the couple of mapping genes labs we will have.

We covered concepts like gene mapping, genetic linkage, and genetic distance within a chromosome, and how they are correlated. We also introduced the concept of CentiMorgan (cM), a.k.a. Map Unit (m.u.), and how it is useful to map genes, based on the results of experimental crosses.

We also used a little applet developed by Paul Lewis, from the University of Connecticut, called demonstration of crossing over. With this application we did simulations on recombination events affecting two loci separated by variable genetic distances. We then introduced the concepts of parental haplotypes/gametes and recombinant haplotypes/gametes, as part of the more practical explanation of genetic linkage.

We also did a quick demo of the software to be used in this lab: DrosophiLab. Students will download this Windows-based free software to simulate experimental crosses in Drosophila melanogaster, and calculate genetic distances between different genes. The labguide is being written and will be posted soon.

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Lecture, chapter 8 - DNA structure

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Rosalind Franklin and her "photo 51"
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Today we started covering chapter 8, on the structure of DNA and chromosomes.

We talked about a little bit of the history of how the structure of DNA was discovered, including the injustice commited towards Rosalind Franklin, who took the X-ray diffraction image known as "photo 51", which was key for Watson and Crick to resolve the structure of the double helix. Her collaborator, Maurice Wilkins showed Watson the picture, without Franklin's knowledge, and the latter failed to acknowledge the fact that HER image put him and Crick on the road to become the icons they officially are today.

Then we talked about the structure of nucleotides and how they are assembled to form the famous DNA double helix.

On Thursday: We will talk about the similarities and differences between DNA and RNA, and will cover the basics of chromosome structure.

Congratulations to Brittany Simmons, the winner of the heritability challenge...!

Have a happy Easter break!

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Lab 05 - Heritability

In today's lab we focused in calculating heritability, the proportion of phenotypic variance explained by genetic differences.

We covered two approaches to calculating heritability:

1. Broad sense heritability: It reflects all possible genetic contributions to a population's phenotypic variance like effects due to allelic variation (additive variance), dominance, or polygenic interactions, as well as matrenal and paternal effects.
2. Narrow sense heritability: It quantifies the proportion of phenotypic variation explained by allelic variation.

We calculated broad sense heritability with data collected from student's fingerprints, specifically total ridge count. And narrow sense heritability will be calculated based on students' heights in inches, as well as the heights of their siblings, parents, and parents siblings.

The heritability challenge (Thursday):

During the exercise I made a mistake when calculating broad sense heritability. Apparently no body caught it. If you can find the mistake and explain the whole exercise correctly to the rest of the class, you will have the chance to earn 5 bonus points. Be prepared, and among those who have the answer I will randomly chose some one to try to get the bonus points.

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Friday, April 3, 2009

EXAM 1

We had our first exam, covering chapters 1 through 6 in the book.

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Lab 04 - Complex patterns of inheritance

In lab 4 students analyzed pedigrees that showed patterns of inheritance that could not be explained by any one of the six modes of Mendelian inheritance covered in class. As part of the pedigree analyses they observed the incidence of incomplete penetrance and variable expressivity of traits.

Students also became familiar with concepts like genetic liability and recurrence risk, and were able to calculate the latter using specific methods that make use of the standard deviation of the population as a tool to infer such information.

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Lecture, chapter 6 - Cytogenetics

From The Cartoon Guide to Genetics
Larry Gonick & Mark Wheelis
© Harper Perennial, 1983 & 1991
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We finished chapter 6, on cytogenetics.

We covered the main cases of autosomal and sex chromosome aneuploidy: Down syndrome (trisomy 21), Turner syndrome (trisomy 18), Patau symdrome (trisomy 13), Klinefelter's syndrome (XXY), and "supermale" syndrome (XYY).
We also discussed structural abnormalities in chromosomes, like deletions, additions, inversions, and translocations.

On Friday: Exam 01
On Monday: Chapter 8, on chromosomes and DNA

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Lecture, chapter 6 - Cytogenetics

A human karyotype
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Today we started chapter 6 on cytogenetics.

We covered karyotypes, chromosome nomenclature, and classification of variation in chromosome number: Polyploidy and aneuploidy. We discussed triploidy and tetraploidy and on Monday we'll start discussing cases of aneuploidy.

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Our "Genetics News Friday" discussion was a failure and a dissapointment. In spite of having tools to acquire information easier than ever before, nobody brought an idea to discuss, and you can find them everywhere!
Remember, genetics is not just a class to get out of the way. It is a field that has plenty of applications and implications in the real world! Reading or listening to genetics-related news is a good exercise, for this class and for life in general.

Again: Other than the traditional sources of information you can also get information from RSS feeds (the news come TO you), and podcasts (some are literally 1 min 20 secs long...! Can it get any easier?). See Monday's entry (March 23) for some extra details.

No discussion may mean questions about genetic-related news in the quizzes. You pick.

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An RSS Feed looks like this (click for full size image)

And the link will take you to something like this (click for full size image)

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Lecture, chapter 5 - Polygenic inheritance

A gradient of skin tones
click on image for a full size pic
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Today we finished covering chapter 5, on polygenic inheritance.

We discussed concepts like distribution of environmental factors, norm of reaction, and heritability. We also discussed the importance of twin studies in complex traits research, and talked about a couple of examples of polygenic traits in humans: skin color and intelligence.

Tomorrow: Chapter 6, on cytogenetics.

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Lab 03 - Epistasis and hypothesis testing

Tuesday, March 24, 2009

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We did our "corny genetics" lab. Students, working in pairs, analized the expected and observed phenotypic proportions of the F2 generation from a dihybrid cross in genetic corn. They used their expectations and their observations to perchorm a chi-sqare test and relate the results to a potentially epistatic interaction.

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Lecture, chapter 5 - Polygenic inheritance

Today we started covering chapter 5, on polygenic inheritance and interaction with the environment.

We discussed the differences between continuous and discontinuous characters, the definitions of polygenic, multifactorial, and complex traits, and the most common approach to studying the inheritance of continuous variation: Quantitative genetics. Quantitative genetics uses many statistical tools as well as some concepts inherent to it, like the genetic version of regression to the mean, phenotypic distribution, norm of reaction, genetic variance, phenotypic variance, and heritability.

Tomorrow: Lab 3, on Epistasis and hypothesis testing.

On Thursday: More about chapter 5.


Note:

Given the success of the end-of-class discussion on Friday, we will continue having "genetics on the news" discussions in the future, with the possibility of including questions in quizzes. I encourage you to use on-line resources to find genetics news, or let them find you. The main sources would be RSS feeds of publications like Nature, Science, or Scientific American (among MANY others), and scientific podcasts.

Some podcasts have been uploaded to the p-drive and the WebCT site (check them out!), but you can find many more on genetics-related sites. You can get them wherever you want to.
If you don't know were to begin just use iTunes (freeware, availale in Windows and Mac OS X versions) to access the iTunes store and download/subscribe to any of the FREE scientific podcasts available.

Remember, you can find the news, and with RSS feeds and podcast subscriptions the news will find you.

Examples of sites with RSS feeds:

• Scientific American
• Nature
• Science Magazine

If you find any other interesting site, let me know.

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