Lecture, chapter 04 - Pedigree analysis in human genetics

Pedigree showing inheritance of an autosomal dominant trait
___________________________________________

We covered most of chapter 4, on pedigree analysis.

We discussed the several inheritance modes that can be studied by pedigree analyses (autosomal dominant and recessive, X-linked dominant and recessive, Y-linked, and mitochondrial), and we introduced the concepts of penetrance and expressivity.

----------------------

Lab 03 - Epistasis and hypothesis testing

Wednesday, December 09, 2009

Genetic corn

____________________________________________________

In this lab we used genetic corn to test a prediction based on Mendelian principles, about the inheritance of two genes.

The color of corn kernels, although just one trait, is controlled by two separate genes (R and C) that affect pigmentation in the aleurone, which may or may not be pigmented. If transparent the color of the kernel will be yellow or white, and when pigmented it will be purple or red. In our case we only had purple and yellow kernels in cobs that were obtained as the F2 generation from a cross from double homozygote parent plants (RRCC x rrcc).

By doing a count of purple and yellow kernels, students were able to predict the phenotypic proportions of yellow and purple kernels. The predictions were compared to the observations and tested using a chi-square test, with a significance level of 5% (α=0.05).

When the hypothesis (observed values = expected values) was rejected, results were explained as the consequence of an epistatic interaction that prevented the R and C genes of showing the phenotypic proportions predicted by Mendelian inheritance.

_______________

Tissue layers on a corn kernel. When the aleurone

is transparent the kernel will show the color of

the endosperm (white or yellow)

----------------------

Lecture, chapter 3 - Mendelian genetics

Today we talked about Mendel's principles, the principle of segregation and the principle of independent assortment. We discussed how Mendel performed the experiments that lead him to formulate his principles and the implications of doing so at the time he did it. We also talked about the re-discovery of his work in the early 1900s, the connection of his findings with the discovery of chromosomes, mitosis, and meiosis, and finally set the stage to discuss some of the variations on Mendel's principles (cases other than complete dominance, multiple alleles, etc.)

----------------------

Lecture, chapter 01 - A perspective on human geneticsLecture, chapter 03 - Mendelian genetics

Today we finished chapter 01, with a discussion of the impact genetics has had and has in society, from eugenics, to biotechnology and the development of the Human Genome Project (HGP).

We started chapter 03, on inheritance of genes (transmission genetics or Mendelian genetics), with a brief discussion of the characteristics Mendel was looking for in the plants he would use for his studies. We, briefly and informally, stated the first of Mendel's principles, and set the stage to discuss the second principle.

----------------------

Lab 01 - Human genetics

Students formed groups of four people to work in the bioethics projects that we will develop during the quarter. Each group proposed one or more topics that are controversial and have a genetic basis. Topics were assigned to groups that proposed them, and in a few cases groups decided to choose a topic suggested by the instructor.

We also did exercise 01, on the basics of studying human genetics by using pedigree analyses. Students did a little mini-survey in their families to find out who had one of the alternative forms of expression of the following traits:

• Hitchhiker's thumb
• Tongue rolling
• Free/attached ear lobe
• Hand folding

Each student learned how to draw and interpret a basic pedigree using such traits in their families, and learned how to figure out the genotypes of each individual in the pedigree.

----------------------

WINTER QUARTER 2009-10Chapter 01 - A perspective on human genetics

We officially started the winter quarter today.

We went over the lecture syllabus and started covering chapter 1 in the book, 'A perspective on human genetics' (or 'a human perspective on genetics'; your choice). We talked about the very basics of what a gene is, what it does and how it is transmitted, and the different approaches to the study of genetics. All these pointing out to how important the study of genetics is in every day's life.

----------------------

Last lecture, chapters 14 and 12 - Biotechnology + Genes and cancer

We met outdoors to enjoy the weather...

We closed the chapter on biotechnology by discussing the use of short tandem repeats (STRs) in gene profiling or fingerprinting.

Then we discussed the first part of the chapter on genes and cancer. We talked about the link between cancer and mutation, the role of mechanisms that control de cell cycle, and cancer originated from mutations in genes related to DNA repair.

Tuesday, May 19: Final exam. Meyer 114, 4-6 pm.

----------------------

Lecture, chapter 14 - Biotechnology

Thursday, May 14, 2009

A gene "chip", a microarray containing an emtire human genome,
used for genetic testing
_____________________________________________________

We continued with the chapter on biotechnology.

We talked about the process of making transgenic mice to use as models of human diseases, the differences between genetic screening and genetic testing, and the main techniques of genetic testing, including those involved in what it is known as pre-implantation genetic diagnosis (PGD).

We finished discussing the possibilities to do genetic testing on an entire genome using microarrays, specifically gene "chips".

---------------------

Lecture, chapter 14 - Biotechnology

Today we started chapter 14 on biotechnology.

We discussed the most basic applications of biotechnology and how it has bben applied to replace older methodologies to produce proteins to treat human diseases (biopharming).

We also discussed the goals of genetically modifying crops, and some of the main concerns that people have about them. We also started discussing how recombinant DNA technology has been used to create transgenic animal model organisms, mainly mice, to study the development of human diseases and test possible treatments to cure them.

----------------------

Lecture, chapter 13 - Mutation

Child with xeroderma pigmentosum a disorder caused by mutations
on genes involved in DNA repair mechanisms
_____________________________________________________

Today we finished the chapter on mutation.

We talked about how insertions and deletions (indels) can affect a nucleotidic sequence depending on how many nucleotides are inserted and whether or not they change the reading frame of the sequence.

Then we discussed the basics of the proofreading and DNA repair mechanisms that cells have in place to fix DNA changes, which happen at a much greater rate than the rate of mutation (reminder: a mutation is a DNA change that gets passed to subsequent generations of cells and/or organisms; it's a DNA change that doesn't get repaired).

We also considered a third category of mutations: allelic expansions, which interestingly enough happen in only one of the alleles in a gene pair. Genes that have trinucleotide repeats undergo mutations in which the number of repeats increase to the point in which the protein they encode for is not functional any more.
We mentioned anticipation, the phenomenon in which a genetic disorder caused by an allelic expansion is expressed in a more severe way, and at earlier ages, generation after generation.

----------------------

Lecture, chapter 13 - Intro to cloning and recombinant DNA technology

Today we finished chapter 13, an introduction to the use of recombinant DNA technology.

We talked about how to clone DNA in vitro, through PCR, and how to analyze DNA that has been cloned, mainly with the techniques Southern blotting and automated DNA sequencing.

Tomorrow: We will finish the chapter on mutation (ch 11).

And now, honoring Kyle and Jackie's request, I introduce you to the cheesiest, geekiest, funniest, and learnyousomethingest song: The PCR song...!

----------------------

Lab 09 - Bioethics debates/presentations

Yesterday, Tuesday May 5, we had our 5 bioethics debates/presentations on the following topics:

• Prenatal diagnosis or screening
• Designer babies
• Genetic privacy
• Emryonic stem cell research
• Gene therapy

The style of the presentation portion ranged from a U.S. Senate hearing to a trial (including witnesses, a jury, and even a really ugly bailiff...). Students engaged in relatively gentle, but still interesting debates on different issues. They were able to express their views and opinions, but also showed to be knowledgeable in the topics they decided to research.

On Thursday: More on chapters 11 (mutation) and 13 (intro to cloning and recombinant DNA)

----------------------

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
_____________________________________________________

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...!!!

----------------------

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]).

----------------------

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!

----------------------

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.

----------------------

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!

----------------------

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.

----------------------

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.

----------------------

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.

----------------------