Behavioral Genetics Week 4: The Human Genome

This week in my Behavioral Genetics class, we learned about the Human Genome.  This included several lectures on genetic variation, which was very interesting to me because it's directly pertinent to Joshua's situation.  It's interesting to see (even in a lightning speed flyover on the subject) how far the field of genetics has come in the last 20 years, and how rapidly it's progressing.  The professor said that he expects knowledge of the human genome will revolutionize medicine, which is exciting. Without further ado, things I want to remember about this week's lesson on the Human Genome...

• DNA provides a code for building proteins, chains of amino acids
• DNA (double strand) is transcribed into RNA (single strand), then translated into proteins.

Gene Structure:
1.  There is an orientation:  5' (upstream) to 3' (downstream).
2.  Upstream (5’) is a regulatory region, a promoter that determines which strand of DNA will be used and where the gene starts.
3. Genes are not continuous DNA sequences, they contain introns and exons (Exons – Expressed, contain the protein coding sequence; Introns – Intervening sequences)

3 surprises about the human genome:
1.  Most of the human genome is non-coding (98.5%) (but non-coding does not mean non-functional).
2.  Humans have a small number of protein coding genes. (Humans have around 21,000 genes.  This is slightly more than a fruit fly and slightly less than a mouse.)
3.  Comparative genetics - "we're all essentially identical twins".  All humans share 99.9% of DNA the same as each other.  But think about overall scale - even though we're mostly the same overall, there are still 6.4 million differences.  Very small changes in our DNA can have rather significant effects.

Genetic Variance Among Us

• Insertions / Deletions - small number of bases (less than 100) missing or added - this is very common
• Copy number variants - large segments of DNA (at least 1000 bases) have been deleted or inserted.  Ex:  22q11.2 (missing about 3 million bases) [This is the type of genetic variance that Joshua has.]
• Aneuploidy - having an extra or missing chromosome (ie Down's Syndrome).  These are fairly rare.
• Organization - differences in how DNA is organized - inversions and translocations.

The Unique Case of the X Chromosome

• Women have two X chromosomes.  Men have an X and a Y chromosome.  
• X Chromosome has a lot more protein producing material than Y chromosome. (2,000 v. 80)
• But women do not produce a lot more protein products than men, because in women, only one X chromosome is active - the other becomes inactive.  
• Different cells will have different X chromosomes turned off.  The timing is random, but it happens early in embryonic development, and once it happens it's permanent - when those cells duplicate, the same X will be turned off.   
• This show that there is a mechanism of genetic regulation.  

Prader Williams and Angelman's:  Two Different Genetic Disorders on the Same Part of the Genome

• Prader Williams:  uncontrolled eating, low muscle tone, cognitive dysfunction.  15q11.2
• Angelman's:  movement and language disorder, behavioral (happy).  Also 15q11.2
• Even though these deletions are de novo, in PW it's always the father's chromosome that's deleted.  In Angleman's, it's always the mother's chromosome that had the region deleted.
• Why should it matter if it was father's or mother's chromosome?
• There are regions where whether you inherited from father or mother makes a very big difference in the expression of the gene.  About 1% of our genomes are imprinted this way.
• Another possibility: uniparental disomy - the child ended up with two chromosome 15s from just the mother, or from just the father, rather than one chromosome 15 from each.
• Another example in nature of genes expressing very differently depending on whether they were inherited from the father or the mother:  ligons (father is lion, mother is tiger - they are large) are very different than tigons (father is tiger, mother is lion - they are quite small).

Epigenetics 
Epigenetics is the study of genetic regulation - differences in DNA expression that is not due to difference in the DNA sequence.  3 examples of this:
1.  X chromosome inactivation
  - Occurs early (in first couple weeks of embryonic development)
  - It's stable - once it becomes inactive, it stays that way
2.  Imprinting - some genes only expressed if inherited from mother, some genes only expressed if inherited from father.
  - Once again, it happens early and it's stable.
3.  Gene expression pattern - what differentiates a muscle cell from a liver cell from a blood cell.
  - Again, happens early and it's stable.

Could factors in our environment cause epigenetic effects?
 - Yes.  Some examples:  maternal malnourisment (increased sensitivity in early embryonic development), grooming in a mice study,