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Re: [SACC-L] cis-regulation and genetics (long)

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  • Mark Lewine
    Andrew, thank you! Your explanations were clear and almost understandable to an ancient like me who never had microbiology because there was little or no
    Message 1 of 34 , Oct 4, 2009
      Andrew, thank you! Your explanations were clear and almost understandable to an ancient like me who never had microbiology because there was little or no information when I was in school. PLEASE consider doing a presentation/panel or just teach-in on the genetics of human evolution needed to teach anthropology...so many of us would benefit...(and please others respond who understand all or most of what he explained about the chemistry of human microbiology)
      Also, let us consider having a SACC meeting soon in the Midwest or East as we have not done so for a while. Remember Akron drew a large meeting years ago, and, with enough warning, if we did Cleveland in a few years, some of us could help bring in some of the key figures for 'Ardi', re-visit the Amish, visit Shaker sites and Museum, take a field trip to a large Hopewell earthwork nearby in Newark...
      ----- Original Message -----
      From: Andrew Petto
      To: SACC-L@yahoogroups.com
      Sent: Sunday, October 04, 2009 12:56 PM
      Subject: [SACC-L] cis-regulation and genetics (long)


      Folks:

      Sorry this is going to take a little explanation. The first part is
      about cis-regulation; it has a link to a free chapter online. The second
      part has a couple of examples of things you can do in a phys-anth (or
      general anth) class about genetics.

      cis-regulation is one of the ways that alleles interact with each other.
      For example, we KNOW that there are dominant and recessive alleles,
      right? If both are present in an individual, the dominant gets
      expressed, but not the recessive. Mendel (and most anthro texts) never
      say why. However, in the last 30 years or so, genetics has been bursting
      with discoveries about how alleles affect each other. Lovtrup was pretty
      much the main bearer of the banner for epigenetics for several decades
      which, it turned out, was often the result of the addition of a simple
      methyl group (CH3) onto one DNA sequence by another that "turned off"
      the first.

      Now, we are seeing that a lot of the non-structural DNA in the genome
      (used to be called junk) has regulatory functions. It provides signals
      that either encourage or inhibit the expression of other DNA with the
      resulting changes in structure.

      "cis" is the term that refers to a molecule in which two components of
      interest are on the same side of the molecular framework of the
      molecule; "trans" is used when they are on opposite sides.

      We can see how this difference in structure works in producing vision.
      In the dark, the main compound in the retina is trans-retinal. When
      trans-retinal is present, you see nothing in those receptors. When the
      light hits the retina, the energy changes the backbone and converts the
      molecule to cis-retinal. Then, cis-retinal interacts with other
      compounds in the retina and causes a variety of biochemical changes that
      eventually result in the activation of the optic nerve.

      So, we have known for some time that there is a difference in
      biochemical activity between cis- and trans- forms.

      Most of what I can find in the genetics literature is that
      cis-regulatory elements serve to activate transcription promoters; so
      they help to activate the compounds that in turn activate the DNA
      sequences; the thinking is that this is important in timing and
      intensity of genetic expression. A great (and accessible) book that I
      just reviewed on these development issues in _Quirks of Human Anatomy_
      by Louis I Held, Jr.

      If you want a more detailed description of cic-regulation with examples,
      here is one place to go:
      http://etd.caltech.edu/etd/available/etd-09252002-111831/unrestricted/1_Chapter_1.pdf

      As far as teaching genetics in an anthro (or basic human bio) class is
      concerned, my practice is always to show how Mendelian genetics works,
      because it shows how things are inherited. I also take the students to
      the OMIM website to show them their favorite genes in the human genome.

      I ask them to search for some disorder of interest (we use Marfan
      Syndrome in the course because it is a good example of pleiotropy). When
      they connect
      (http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606),
      they first find that there are usually two or more loci involved even in
      these "simple" genetic traits. Marfan, for example, shows relevant
      "hits" on Chromosomes 7 and 15. The interest for my anatomy class is
      FBN1, which is located at 15q21.3.

      Then I have them look at something polygenic. I have chosen Bombay
      Phenotype because it is based on the ABO blood group, and everybody
      "knows" about that, right? Here is a good overview
      (http://anthro.palomar.edu/blood/Bombay_pheno.htm), but the problem
      actually came up in my human anatomy class when a student approached me
      and said, "I have always wondered, and none of my science teachers could
      give me a good explanation. My mom is type A and my dad is type O, but I
      am AB. How could that happen?"

      It gave me pause, for sure, but I said I would check and I found the
      Bombay Phenotype. Even though we usually see ABO as a simple trait (one
      allele: one phenotype), it turns out that there are at least 2 alleles
      necessary to get the A, B, and AB types. The first is the "H" allele
      (and a lot of anthropological texts discuss this, though in reference to
      antigens in the saliva). The enzyme from the H allele builds a
      glycoprotein scaffold (just some carbohydrate and amino-acid molecules
      combined into a single compound) on the surface of the red blood cells.
      This scaffold has no antigenic activity; if you have only the scaffold,
      you are type O. Then the alleles for types A and B (and AB) attach OTHER
      molecule to the scaffold, and these molecules are antigenic, and so they
      DO cause a reaction in our blood tests.

      So, ABO testing is still a PHENOtypic analysis, with the assumption that
      there is a close relationship between phenotype and genotype (there is,
      but it is not 1:1). AND, in the analysis, we are testing for the
      presence of the A and B /_*antigens*_/, NOT the presence of the A and B
      _/*alleles*/_. Absence of antigens is PRESUMED to relate to absence of
      alleles (but remember, this is a clinical test that is used to determine
      whether blood donors are compatible with recipients, and so in this case
      it is the antigens, not the alleles that matter). So, absence of the
      antigen makes us conclude the individual is type O and makes us INFER
      that there are no alleles for A or B.

      In the Bombay Phenotype, there ARE allelles for type B in the parent,
      but no functional alleles for the H enzyme. There is no place to put the
      antigens on the red blood cell's membrane, so they do not "stick" and
      the result is that there is also no antigenic activity in the sample,
      even though the B allele is present in the genome, and so the antigenic
      test comes out negative. BUT, in a classic Mendelian form of
      inheritance, when daughter gets a competent H allele from her mother,
      Dad's B allele is expressed.

      We also checked the blood types of cousins and other collateral
      relatives and saw the same pattern from descendants of the same
      grandparental units. So, it was a relief to be able to tell the student
      that the man she thought was her father probably really was AND it
      became a great example of the interactions among genes that make
      genetics interesting.

      It also gets to a main point, which is a great Socratic-type question to
      ask in class: If genes are designed to make accurate copies of
      themselves in cell divisions of all types, how is it possible for genes
      to produce biological variation? (Hint: the answer is NOT mutation,
      since that is pretty wasteful; but RECOMBINATION. The main objective of
      sexual reproduction is to produce individuals with new combinations of
      alleles.) The Bombay phenotype is an example of how mixing up genes can
      produce different phenotypes --- and without getting into the
      biochemistry necessary to explain cis-regulation to undergrads who took
      your phys anth courses to avoid this stuff in the bio classes.

      Anj Petto

      Philip Stein wrote:
      >
      >
      > Mark, don’t expect a lucid explanation of cis-regulation from me. It
      > has become very apparent that the basic Mendelian genetics that we
      > teach in physical anthropology has become very simplistic.
      >

      --
      Andrew J Petto, PhD
      Senior Lecturer
      Department of Biological Sciences
      University of Wisconsin - Milwaukee
      PO Box 413
      Milwaukee WI 53201-0413
      414.229.6784
      fax: 414.229.3926
      ajpetto@...
      https://pantherfile.uwm.edu/ajpetto/www/index.htm
      http://www.uwm.edu/Dept/Biology/Docs/Faculty/ajpetto.html

      *************
      Now Available!!! Scientists Confront Intelligent Design and Creationism.
      https://pantherfile.uwm.edu/ajpetto/www/scc2.htm
      *************

      "There is no word in the language that I revere more than teacher. None. My heart sings when a kid refers to me as his teacher and it always has."

      -- Pat Conroy
      The Prince of Tides

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    • Monica Bellas
      I didn t get a chance earlier to thank everyone for your suggestions. I am incorporating a few ideas for my syllabus, and will also be speaking to them the
      Message 34 of 34 , Dec 20, 2009
        I didn't get a chance earlier to thank everyone for your suggestions. I am incorporating a few ideas for my syllabus, and will also be speaking to them the first day of class about how I managed to get through college despite marriage, two kids, and working.

        Thanks again!

        Monica Bellas

        Cerritos College

        Norwalk, CA




        To: SACC-L@yahoogroups.com
        From: lloyd.miller@...
        Date: Thu, 29 Oct 2009 17:02:34 -0500
        Subject: Re: [SACC-L] Suggestions for student/prof expectations





        Monica,

        I did almost the identical thing some years ago (I retired in 2000).
        I scolded the entire class for a total of about 15 minutes, then
        walked out, telling them that if they wanted to talk to me, I'd be in
        my office for the rest of the class hour. I guess they were somewhat
        stunned; the few who did come by said as much and something to the
        effect of, "Gosh, we didn't know you cared that much!"

        So in subsequent syllabi, I included a section of what I expected of
        them (courtesy toward me and each other, attentiveness, preparation
        for class--I can't remember it all, but something like if you're not
        going to at least show good student behavior, don't come to class. I
        offered extra credit for good attendance). They could expect from me
        that I would also be prepared for class, that I would grade and return
        to them promptly tests and other assignments. I would show them the
        respect due them and treat them fairly and equitably; again, I can't
        remember all I had, because in later years I changed my message to
        them somewhat, but kept the same intent and spirit.

        I will send you a pdf of several pages of a syllabus by separate email
        because the listserv doesn't accept attachments. One item on it is
        titled, "Some Characteristics of Successful Students" that I got from
        a colleague in psychology. It presents good student behavior to them
        impersonally as a study rather than as a direct exhortation from me to
        them. I'll also send you a pdf of Tom Wayman's delightful poem, "Did
        I Miss Anything?" that we reprinted in SACC Notes, Vol. 12, No. 2 2006
        (in case you didn't save all your issues of SACC Notes in gold-
        embossed, leather-bound volumes). :)

        Lloyd

        On Oct 29, 2009, at 3:39 PM, Monica Bellas wrote:

        >
        > I have a question which I'm sure the many experts on the listserv
        > can answer. I just scolded (very strongly) my students in one of my
        > sections for not reading their textbook and not studying for their
        > exam. I'm seriously thinking about included a list of "expectations"
        > for future students, which would be part of my syllabus. (I would
        > also include a list of what they should expect from me.) Has anyone
        > done this before? If so, what did you include? (Please note I'm not
        > talking about an "Honor Code," but what I expect from them.)
        >
        > Thanks so much,
        >
        > Monica Bellas
        >
        > Cerritos College
        >
        > Norwalk, CA
        >
        >
        > [Non-text portions of this message have been removed]
        >
        >

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