LectureChapter 10 - From proteins to phenotypesChapter 11 - Mutation

We continued a discussion on pharmacogenetics, or studying phenotypes in terms of how we react to chemicals in our bodies.

We did the popular genetic test on tasting phenylthiocarbamide (PTC), a Mendelian trait easy to diagnose. Some people have the dominant allele that manifests in being able to taste PTC (dubbed "tasters", with the genotype TT or Tt), and some people have only the recessive allele, which prevents them from tasting the chemical compound (dubbed "non-tasters", with genotype tt).  Those who can taste it perceive a bitter flavor.

In our class there were 16 'taster' vs. 6 'non-taster' students.  A fast survey revealed that tasters have a tendency to dislike foods or beverages that have chemicals similar to PTC, like dark beer (question limited to students over 21 years of age), coffee, strong cheeses, artificial sweeteners, and spicy foods. Interestingly enough, most tasters also liked vegetables like broccoli and cabbage, which should be bitter for them.  Non-tasters tended to like such foods and beverages.

We discussed the scope of ecogenetics, the field that studies our responses to chemicals in the environment.

We started the chapter on mutation by providing a definition and outlining the conditions in which a mutation that has a phenotypic effect can be detected.

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Lab 07 - Gene mapping in humans

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

In humans, we must rely on pedigrees. In this lab we considered three different pedigrees showing linkage between a genetic disorder and another trait (easily observable). 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, chapter 10 - From proteins to phenotypes

Today we started chapter 10 on how proteins can affect our phenotype.

We started with a brief discussion of protein function and then ways in which mutations can affect our phenotype by causing changes in the sequence of amino acids of enzymes (which may impact metabolic pathways), receptor proteins and transport proteins.  We provided examples using several diseases caused by such mutations.

We started a discussion on pharmacogenetics, or how we can study phenotypes in terms of how we react to chemicals in our bodies.

Up next:  Can you can you not taste phenylthiocarbamide?

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Lecture, chapter 9 - From genes to proteins

Today we discussed what cytoplasmic components are crucial for the process of translation.  We described the main characteristics of ribosomes, amino acids and tRNA.

We then described the actual process of translation, dividing in its phases of initiation, elongation and termination.  We followed with a discussion of the fate of synthesized polypeptides and the features of protein structure.

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Lab quiz 01

Today we had our first lab quiz.  Stats:

(click on pic for a full size image)

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Lab 06 - Gene mapping - Drosophila

Tuesday, April 12, 2011

Today we did lab 06, on mapping genes in Drosophila.

We discussed concepts like linkage, recombination, crossing over, and as a consequence how phenotypic categories deviate from Mendelian proportions. We mentioned how genes that are in the same chromosome may also be unlinked, if the distance between them (measured in centimorgans (cM) is big enough.

Using DrosophiLab, a crossing-over simulator (from Paul Lewis' lab), and paper and pencil, students learned:

• How to determine the distance between two genes in the same chromosome (measured in cM or map units (M.U.))
• The effect of the distance between genes and the size of a chromosome in the frequency of recombinant chromosomes during meiosis
• How to map genes based on gene distances
• How to map genes and find the distances between them based on phenotypic data (resulting from simulated crosses).  We did this for three genes, using a three-point test cross.

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Chapter 9 - From genes to proteins

Today we discussed the way in which genetic information is coded in DNA.  We introduced the genetic code, some of its properties and some of its implications.

Then we moved on to talk about the transcription process.  We mentioned its steps (initiation, elongation, and termination), and the processing that a mRNA molecule must undergo before being exported to the nucleus (5' capping, polyadenylation, intron splicing).

As an introduction to the process of translation, we explained what amino acids are and how they are linked into polypeptides.  On Wednesday we will talk about other cytoplasmic components important for
translation, and about the translation process itself.

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LectureChapter 8 - DNA structure and chromosomal organizationChapter 9 - From genes to proteins

Today we discussed the basics of RNA structure and pointed out basic differences between it and DNA.  We then had an overview of how DNA is condensed into chromosomes and how it is replicated.

Watch the following video or access this link to understand the main features of the DNA replication process

We also started chapter 9, on how genetic information is transcribed into mRNA and translated into proteins.  We briefly recapped how Beadle and Tatum confirmed that there was a connection between genes and proteins in the 1940sand how their famous quote ("one gene, one enzyme") has been modified, as discoveries have been made, to make it more accurate.

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Chapter 8 - DNA structure and chromosomal organization

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Rosalind Franklin and her "photo 51"
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We continued discussing the history of how the structure of DNA was discovered, including the injustice  (alleged by many) 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.

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Lab 05 - Heritability

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

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/recessiveness, polygenic interactions, and well as maternal and paternal effects.
2. Narrow sense heritability: It quantifies only the proportion of phenotypic variation explained by additive contribution of the genes that control the trait, ignoring all other genetic contributions.

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

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LectureChapter 6 - CytogeneticsChapter 8 - DNA structure and chromosomal organization

Today we finished the cytogenetics chapter, with a discussion on uniparental disomy (UPD) and fragile sites, the remaining chromosomal abnormalities.

And we started on chapter 8, on DNA structure and chromosomal organization, with a brief discussion on some science history events that led to the discovery of the structure of DNA.  On Wednesday we'll pick up on  the drama that unfolded around Rosalind Franklin's (involuntary? not-acknowledged?) involvement in the process of deciphering the structure of the now famous double helix.

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Exam 1

Friday, April 1, 2011

Stats on exam 1:

(clic pic for full size image)

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Lecture, chapter 6 - Cytogenetics

Today we discussed the several cases of autosomal and sex chromosome aneuploidies:  Their frequency, symptoms, and consequences for an individual's life.  Polyploidies and aneuploidies are cases of alterations in chromosome number.

We also introduced the concept of chromosomal structural alterations.  We mentioned the various categories (deletions, duplications, inversions and translocations) and started discussing them.

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Lab 04 - Inheritance of complex traits

Today we practiced pedigree analysis when a trait is controlled by one or several genes and environmental factors. Students learned how to identify a complex trait on a pedigree and to estimate the most plausible mechanism explaining the pattern of inheritance observed in a pedigree.

We introduced the concepts of threshold traits and genetic liability, and used them to calculate the risk of parents conceiving a child affected by a multifactorial disease (an example of a threshold trait)

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Lecture, chapter 6 - Cytogenetics

A human karyotype
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Following with the chapter on cytogenetics we discussed the nomenclature of chromosomes, how to produce a human karyotype, including the different chromosome banding and painting techniques, and methods to obtain cells from fetuses and adults to produce a karyotype.

We introduced the topic of variations in chromosome number, including polyploidy and aneuploidy;  we discussed the most common causes for each abnormality.

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LectureChapter 5 - Polygenic and multifactorial inheritanceChapter 6 - Cytogenetics

Today we discussed one of the most important concepts in quantitative genetics.

We defined heritability and talked about some of its implications. We discussed the use of twin studies as tools the estimate heritability of different traits, and the importance of using both, monozygotic (MZ) and dizygotic (DZ) twin studies.

We discussed a few examples of multifactorial traits in humans: Skin color, IQ, and obesity.

Then we started discussing the chapter on cytogenetics, a field that focuses on studying chromosomes, using karyotypes as the main tool.

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Lecture, chapter 5 - Polygenic and multifactorial inheritance

We started covering quantitative genetics, the subfield of genetics that studies polygenic and multifactorial inheritance based on observations on phenotypic variation.

We discussed the principle of regression to the mean and how statistics is used as an important tool in quantitative genetics. We focused on concepts that are specific to quantitative genetics, such as phenotypic distribution and distribution of environments.

We mentioned features of the interaction of genes and environment as preparation to discuss the concept of heritability.

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Lab 03 - Epistasis and hypothesis testing

Genetic corn

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Yesterday 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 kernels, students were able to predict the phenotypic proportions of purple and yellow kernels. The predictions were compared to the observations and tested using a chi-square test, with a significance level of 5% (0.05, numerically, but not conceptually equal to α).

When the hypothesis (observed counts = expected counts) was rejected (if it 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.

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Lecture, chapter 5 - Polygenic and multifactorial inheritance

After finishing chapter 4 on pedigree analysis (discussing age-related phenotypic expression, penetrance, and expressivity), we started chapter 5, on multifactorial and polygenic inheritance.

We discussed the differences between continuous and discontinuous traits, and how they are related to the number of genes that affect them. Discontinuous traits must be described in terms of measurements taken in a population rather than qualitatively describing individuals. We defined complex, multifactorial, and polygenic traits.

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Why are fruit flies important for us?

Audio slideshow screenshots
Clockwise: A normal fruit fly next to another with a liver disease, white-eyed mutant flies feeding, a collage of epifluorescence images of flies internal organs or systems, and a fruit fly brain with neurons that control mating, fluorescing in green

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Research in fruit flies, Drosophila, specially D. melanogaster, has been fundamental for enhancing our knowledge of genetics as a whole and of human genetics in particular, since we share about 60% of our genes with them. In lab we have used software that simulates controlled crosses of fruit flies with specific mutations, and in the next few weeks we will perform more complex simulations.

But fruit flies are also used in other areas of research. Check out this audio slideshow, produced by the BBC, on the use of fruit flies in neurophysiology research. Some of the general principles outlined by the researcher apply to genetics research too. The system to breed the flies (jars with growth media, covered with cotton or gauze) is the same as in genetics research.

BBC Audio slideshow: Fruit flies - up close

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