LectureChapter 10 - From proteins to phenotypesChapter 11 - Mutation

Today we finished chapter 10 by discussing the focus of the field of ecogenetics, an area of genetics concerned with how we react to chemicals in the environment based on our genotypes (how we react is our phenotype).

We then started the chapter on mutation summarizing how mutations that are observable in the phenotype have been traditionally studied, including how their rate has been measured (a task that is easier in the case of autosomal dominant diseases).

We discussed the factors that cause different genes to have different mutation rates and introduced the main agents (mutagens) that cause mutations.

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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 discussed the effects of genotypes on how an individual reacts to chemicals, which is the scope of pharmacogenetics, and how an individual reacts to chemicals in the environment, the scope of ecogenetics.

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Lecture, chapter10 - From proteins to phenotypes

Today we examined the role of different kinds of proteins in determining our phenotype and how mutations may affect it.

We had examples on enzymes, transport proteins and receptor proteins.

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Lab quiz 1

Lab quiz 1 stats:

(click on pic for full size image)

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Lab 06 - Gene mapping in Drosophila

Today we did lab 06: mapping genes in Drosophila.

We discussed concepts like linkage, recombination, crossing over, and how phenotypic categories deviate from Mendelian proportions because of these phenomena. 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)

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Lecture, chapter 9 - From genes to proteins

Today we covered the remaining of chapter 7, mainly focusing on the process of translation.

We discussed the importance of the remaining cytoplasmic components (ribosomes and tRNA), and then we described the actual process of translation, breaking it down in its stages (initiation, elongation, and termination).

We commented on the structure of polypeptides and the events they undergo after translation (folding and different possible types of modification).

Tomorrow

• Lab 6: Gene mapping in Drosophila (computer lab)
• Lab quiz 1 (bring a calculator)

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Lecture, chapter 9 - From genes to proteins

Today we started our chapter on how genetic information is transferred into entities that affect, or in some cases are, our phenotype: Proteins.

We discussed a little bit of the history of how the link between genes and proteins was discovered, the basics of protein structure and the genetic code, and did an overview of transcription and mRNA processing.

In the next lecture we will discuss the process of translation.

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Lab 05 - Heritability and quantitative traits

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/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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Lecture, chapter 8 - Nucleic acids

Today we finished the chapter we started yesterday, on nucleic acids.

Yesterday we talked briefly about the history of the study of nucleic acids and some of the basic structure and functions of nucleic acids , including a comparison of the characteristics of DNA and RNA.

Today we talked about the implications, for the understanding of genetics, of the discovery of the structure of DNA in the 1950s, the process of DNA replication, the mechanism in which DNA is compacted into chromosomes.

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Exam 1

Stats:

(click on pic for full size image)

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Lab 04 - Inheritance of complex traits

Today we practiced pedigree analysis when a trait is controlled by 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

Today we finished the chapter on cytogenetics with a discussion of the effects of abnormalities on the structure of chromosomes, rather than in the number of them.

Among structural abnormalities we focused on translocations (reciprocal and Robertsonian). We also discussed uniparental disomy (UPD) and the presence of fragile sites.

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LectureChapter 5 - Polygenic and multifactorial inheritanceChapter 6 - Cytogenetics

We finished the chapter on polygenic and multifactorial inheritance with a discussion of the importance of twin studies in studying heritability and on some human complex traits whose relative importance of genetic and environmental factors is still not completely understood: skin color, IQ, and propensity to obesity

We started the chapter on cytogenetics, with an overview of chromosome structure and nomenclature, and the process of making a human karyotype. We followed by discussing abnormalities in chromosome number: polyploidy and aneuploidy (we described some specific cases).

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Lab 03 - Epistasis and hypothesis testing

Genetic corn

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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.

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Lecture, chapter 5 - Polygenic and multifactorial inheritance

We continued the lecture we started yesterday, on polygenic and multifactorial inheritance, a field of genetics that departs from the Mendelian approach. Although individual genes behave according to Mendel's principles, traits that are controlled my more than one gene or are affected by the environment don't show Mendelian proportions in the phenotype of offspring generations.

We defined complex traits, including polygenic and multifactorial, and we introduced the concept of quantitative genetics. We discussed some concepts that are important in the field, like phenotypic distribution, distribution of environments, norm of reaction, and heritability.

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Lecture, chapter 4 - Pedigree analysis in human genetics

Today we finished chapter 4.

We covered the remaining modes of inheritance in human mendelian genetics: X-linked recessive, Y-linked, and mitochondrial. We studied examples of some of those.

We than discussed variations in phenotypic expression, mainly age-related phenotypic expression, penetrance, and expressivity, and provided a few examples, including , interestingly enough, one of the students! (good times!)

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Lab 02 - Mendelian genetics

Today we completed lab 2, in which principles of mendelian genetics were studied through computer simulations of fruit fly (Drosophila melanogaster) crosses.

We used DrosophiLab to simulate crosses between wild type flies and mutants for the autosomal genes vestigial wings and sepia eyes, and the X-linked gene white eyes. By doing so students were able to demonstrate the principles of segregation and independent assortment.

• Video on how to use DrosophiLab

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Lecture, chapter 4 - Pedigree analysis

Following on the pedigree analysis chapter, we discussed the advantages of using a catalog of human Mendelian traits: The Online Mendelian Inheritance In Man (OMIM) catalog, hosted by the NCBI website. In OMIM you can find a wealth of information on human traits that are inherited in a Mendelian fashion, from the symptoms of a genetic disorder and how to diagnose it, to details in the molecular genetics and published papers on the trait or disease.

Then we introduced the several modes of inheritance of human Mendelian traits.

• Autosomal - dominant and recessive
• X-linked - dominant and recessive
• Y-linked
• Mitochondrial

We described the characteristics of the autosomal and X-linked dominant modes of inheritance.

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LectureChapter 3 - Mendelian geneticsChapter 4 - Pedigree analysis

Yesterday we finished chapter 3, on Mendelian genetics.

We discussed more complex phenotypes that made Mendel's principles harder to study in many organisms, and how they do not conflict with them when considering the genotypes. Such phenotypic variations to Mendel's theme are:

• Incomplete dominance
• Codominance
• Multiple alleles
• Gene interactions (mainly epistasis)

We also started chapter 4, on pedigree analysis.

We briefly revisited the reasons for which human genetics cannot be studied experimentally and introduced the modes of inheritance of human Mendelian traits.

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