Methods of Inheritance

For most of my students, this will be a review of stuff you did in Freshman/Sophomore Biology. It is vital background which you will need to build on.  So, if you DON'T know this, you need to learn it.  If it is EASY for you, feel free to skip it.

Try these problems:
1. In mice, the allele for brown fur is dominant over white fur.  A pure breeding brown mouse is mated to a pure breeding white mouse.  What are the expected genotype and phenotype ratios?
2. A mouse from the offspring in problem 1 is mated to a white mouse.  What are the expected phenotype and genotype ratios?
3. Two mice from the offspring of the cross in problem 1 are mated.  What are the expected phenotype and genotype ratios?

[answers are at the end of this post.

If these three problems were difficult for you to answer, you should watch the first 5 minutes of this video from Mr. Anderson at Bozeman Science.  Otherwise, you can continue on to the next problem.

In some cases, two alleles mix to create a phenotype.  These cases are called incomplete dominance and codominance.  In incomplete dominance, the phenotype produced is intermediate.  In codominance, the phenotype produced is a mix of the two.  In reality, this is probably an unimportant distinction, but you can still find it in textbooks and on standardized tests.  Here's a sample problem:

4. Blood types A and B display codominance.  An individual homozygous for blood type A and an individual homozygous for blood type B have kids.  What are the odds that they will have a child with blood type A?  B?  AB?
5. Two individuals with blood type AB mate.  What are the odds that their children will have blood type A? B? AB?

If you had difficulty with problems 4 and 5, begin the video above at about 4:30 and watch the portion about snapdragons.

Some genes are located on the sex chromosomes.  Genes located on the X chromosome are particularly interesting since male humans only get one copy of the X chromosome (termed hemizygous) where as females get two copies.

6. The gene for red-green color vision is located on the X chromosome.  R = normal vision, r = red/green colorblind.  A man with normal vision marries a woman with normal vision whose father was colorblind.  What are the odds of having a color blind boy?  a color blind girl?

If you had difficulty with problem 6, start watching the video at 5:46.

You can get more practice with this type of problem here:
Arizona Monohybrid Crosses
It is vital that you have a good solid foundation with monohybrid crosses.

The Bozeman video goes on to describe how to do dihybrid crosses.  This is great and you should watch it if you aren't familiar with them.  I will teach you a way to do these that is much simpler than writing out 16 square crosses.

We will begin our investigation into inheritance with dihybrid crosses.

Taste genetics

Everyone knows that the tongue allows you to taste.  But how does it work?  It all comes down to ligand-receptor binding.  The diagram below (from learn genetics) shows the connection between the anatomy of the tongue and the cellular location of receptors.

The receptor we are studying in class is the TAS2R38 receptor which binds to the compound phenylthiocarbamide (PTC).  Binding sends signals to the brain which are interpreted as bitter.

What happens if you can't make a working copy of the PTC receptor?

The PTC receptor is a membrane-bound protein made by a ribosome reading an mRNA.
The mRNA is transcribed from DNA found in the nucleus (and then processed).
Every cell in your body has the same DNA in its nucleus.  The PTC gene is expressed (turned on) in tongue cells.

Here is the DNA sequence for the PTC gene:

        1 cctttctgca ctgggtggca accaggtctt tagattagcc aactagagaa gagaagtaga
       61 atagccaatt agagaagtga catcatgttg actctaactc gcatccgcac tgtgtcctat
      121 gaagtcagga gtacatttct gttcatttca gtcctggagt ttgcagtggg gtttctgacc
      181 aatgccttcg ttttcttggt gaatttttgg gatgtagtga agaggcaggc actgagcaac
      241 agtgattgtg tgctgctgtg tctcagcatc agccggcttt tcctgcatgg actgctgttc
      301 ctgagtgcta tccagcttac ccacttccag aagttgagtg aaccactgaa ccacagctac
      361 caagccatca tcatgctatg gatgattgca aaccaagcca acctctggct tgctgcctgc
      421 ctcagcctgc tttactgctc caagctcatc cgtttctctc acaccttcct gatctgcttg
      481 gcaagctggg tctccaggaa gatctcccag atgctcctgg gtattattct ttgctcctgc
      541 atctgcactg tcctctgtgt ttggtgcttt tttagcagac ctcacttcac agtcacaact
      601 gtgctattca tgaataacaa tacaaggctc aactggcaga ttaaagatct caatttattt
      661 tattcctttc tcttctgcta tctgtggtct gtgcctcctt tcctattgtt tctggtttct
      721 tctgggatgc tgactgtctc cctgggaagg cacatgagga caatgaaggt ctataccaga
      781 aactctcgtg accccagcct ggaggcccac attaaagccc tcaagtctct tgtctccttt
      841 ttctgcttct ttgtgatatc atcctgtgtt gccttcatct ctgtgcccct actgattctg
      901 tggcgcgaca aaataggggt gatggtttgt gttgggataa tggcagcttg tccctctggg
      961 catgcagcca tcctgatctc aggcaatgcc aagttgagga gagctgtgat gaccattctg
     1021 ctctgggctc agagcagcct gaaggtaaga gccgaccaca aggcagattc ccggacactg
     1081 tgctgagaat ggacatgaaa tgagctcttc attaatacgc ctgtgagtct tcataaatat
     1141 gcc

This DNA sequence is transcribed into an mRNA.  The mRNA is read to create a protein.  Here is the amino acid sequence of the protein that is a functional receptor.  Note that each letter corresponds to one amino acid.

MLTLTRIRTVSYEVRSTFLFISVLEFAVGFLTNAFVFLVNFWDV
VKRQALSNSDCVLLCLSISRLFLHGLLFLSAIQLTHFQKLSEPLNHSYQAIIMLWMIA
NQANLWLAACLSLLYCSKLIRFSHTFLICLASWVSRKISQMLLGIILCSCICTVLCVW
CFFSRPHFTVTTVLFMNNNTRLNWQIKDLNLFYSFLFCYLWSVPPFLLFLVSSGMLTV
SLGRHMRTMKVYTRNSRDPSLEAHIKALKSLVSFFCFFVISSCVAFISVPLLILWRDK
IGVMVCVGIMAACPSGHAAILISGNAKLRRAVMTILLWAQSSLKVRADHKADSRTLC

Below are five mutations of a single nucleotides that produce non-functional PTC receptor proteins.  I have highlighted these nucleotides in yellow in the DNA sequence above.

In your nucleus, you have 46 chromosomes in 23 pairs.  One of each pair comes from your mother, the other from your father.  The image below shows the 23 different chromosomes.  The TAS2R38 gene is located on chromosome 7.

Let's imagine that you inherited a copy of functional TAS2R38 from mom as well as one from dad.  We would call you homozygous for the taster allele.  Would you be able to taste PTC?

Let's imagine that you inherited a mutated copy of TAS2R38 from both your mother and your father.  We would say you were homozygous for the nontaster allele.  Would you be able to taste PTC?

Now, let's imagine you were heterozygous.  You got one functional copy from one parent, but a nonfunctional copy from the other.  Would you be able to taste PTC?

You probably already know about dominant and recessive alleles.  Dominant alleles are said to "mask" the presence of recessive alleles.  Hopefully, you answered that heterozygotes can taste PTC (they have the taster phenotype).  That would make the taster allele dominant.

So, the dominant allele is due to a functional copy of a protein, while the recessive allele is a nonfunctional copy.  This is usually the case for genes that show traditional Mendelian dominant/recessive relationships.  

Here is a good video from Howard Hughes Medical Institute on PTC:

http://media.hhmi.org/hl/11Discussion1.html

Structure of genes

We've discussed the structure of genes in class. This activity should help reinforce these concepts and introduce you to some powerful tools in bioinformatics. Identify a protein you are interested in. Search for your protein on Wikipedia.  I choose Wikipedia because it is easy to access and had a lot of information in a format that is presented simply.  We will use it as a jumping off point to the National Center for Biological Information (NCBI) -- which is a reliable source of information.  Because Wikipedia is most complete for human proteins, I encourage you to choose a human protein.

I'm using hemoglobin for my example.  Search Wikipedia for your protein (Hemoglobin). Notice that hemoglobin has 3 subunits. I am going to choose HBA1 for my study. I click on HBA1.

At right is part of the page for Hemoglobin subunit alpha 1.  For the purposes of this exercise, you want to compare mRNA sequences, so click on RefSeq(mRNA)

Scroll down the the bottom of the page that opens and you will find the DNA sequence corresponding to the mRNA as shown below for hemoglobin subunit a.  

This is the mRNA sequence from a eukaryote.  Which of the following does it contain?

1. Promoter
2. Start codon
3. Stop codon
4. Introns
5. Exons

ORIGIN      
        1 actcttctgg tccccacaga ctcagagaga acccaccatg gtgctgtctc ctgccgacaa
       61 gaccaacgtc aaggccgcct ggggtaaggt cggcgcgcac gctggcgagt atggtgcgga
      121 ggccctggag aggatgttcc tgtccttccc caccaccaag acctacttcc cgcacttcga
      181 cctgagccac ggctctgccc aggttaaggg ccacggcaag aaggtggccg acgcgctgac
      241 caacgccgtg gcgcacgtgg acgacatgcc caacgcgctg tccgccctga gcgacctgca
      301 cgcgcacaag cttcgggtgg acccggtcaa cttcaagctc ctaagccact gcctgctggt
      361 gaccctggcc gcccacctcc ccgccgagtt cacccctgcg gtgcacgcct ccctggacaa
      421 gttcctggct tctgtgagca ccgtgctgac ctccaaatac cgttaagctg gagcctcggt
      481 ggccatgctt cttgcccctt gggcctcccc ccagcccctc ctccccttcc tgcacccgta
      541 cccccgtggt ctttgaataa agtctgagtg ggcggc
//

Select your sequence and copy it to your clipboard.

Go to the ORF finder at NCBI 

Paste your sequence into the query box and hit OrfFind (the button is oddly placed above the data entry box).  You will get something that looks like this:






My translated sequence is in the +2 frame and is 429 bases long.

Answer these questions for your sequence:

What is shown in blue/green?
How long is the translated portion?
Are there any untranslated portions?
Which frame is translated?

Next, take your sequence and go to nucleotide blast (blastn) at NCBI.

Copy your sequence into the query box.  Select "human genomic + transcript in the database block.

Click blast.

When the results are shown, select "human genome view" from the other views option.

This will take you to a screen which will show you which chromosome your gene is on.

My protein, hemoglobin a is on chromosome 16.

What chromosome is your gene on?

If you click on the chromosome, you will go to the map viewer.  Find a region that shows high identity with a red box in the gene seq map (3rd line) and click on the blue text.  Select "Sequence Viewer".











Selecting sequence viewer will bring up something that looks like this:







Dark green boxes with arrows are exons, light green boxes are untranslated regions of the mRNA and non-boxed green lines are introns.  I can see that Hemoglobin a has two introns and 3 exons.  I can also see the 5' and 3' UTR's.  If I were to scroll to the left on this sequence, I should be able to find the promoter sequence.

How many exons is the gene composed of?
How many introns does it contain?
Can you find your 5'UTR and your 3'UTR?
Where would you expect to find your start and stop codons?