Biology 1a Lecture 25

Overview

Today is a 51 minute lecture on human genetics.  This is an alright talk.  Things can get deeper naturally.

Details

MicroRNAs or miRNAs bind to the 3′ UTR region.  The miRNA binds to a complementary sequence.

The exome is all the exome or protein coding regions of the genome.  It’s about 1-2% of the total genome.  The exome costs $2300 to sequence.  The goal is to make full genome sequencing under a thousand dollars.

The human genome is 3.2 billion nucleotide bases with 25,000 genes.  Sequencing costs are going down dramatically.  It is probable that your own genome will be sequenced in the next ten years.  About 503 miRNA encoding genes.  Half the proteins made are enzymes, half are structural proteins.

There are about 3 million SNPs or 1% of the genome.  15K in protein coding regions.  20% of SNPs are unique or private.

Synonymous mutations do not change the amino acid.  Non-synonymous mutations do change the amino acid sequence.  Non-sense mutations create a premature stop codon.  On average, the mutation rate is 10^-8 base pairs/generation

Hardy Weinburg Equalibrium: Allele frequencies achieve equilibrium as long as mating is random.  This is a simplification, but it’s his plantation.  Recall that an allele is just a different form of a gene.  I’m not going to go into the math if he’s just blasting through it.

Epigenetic changes are also heritable.  They are also changes to the structure of DNA but not the sequence.  DNA methylation in man uses two classes of DNA methylase.  De nove methylase can establish new patterns on an unmethylated subtrates.  Maintenence methylases only methlate DNA that has been methlyated before.  Recognizes homomethlyating substrates.

X chromosome dosage compensation: women get two X’s.  Men get XY.  At the 1000 cell stage, the blastula stage, one of the X chromosomes is inactivated.  It exists as a Barr body at the edge of the nuclei.  XIST is a huge miRNA that coats the X chromosome.

Review

Cochlea: scala vmt vestibuli, media, tymponi

Extraoccular Innervation: 3,4,6

Tissues: connective, muscular, nervous, epithelial

Rods for dark, cones for light

Fovea contains 35K cones

Taste: sour, salty, sweet, bitter

G = H -TS

PV = nRT

K = products/reactants

Brain: diencephalon, cerebrum, cerebellum, brainstem

Brainstem: midbrain, pons, medulla oblongata

SNS = fight or flight PNS = rest of digest-

Biology 1A: Lecture #25:

Lecture 25:

Human Genetics and Epigenetics:

22,550 different protein coding genes.

503 miRNA

Many Non-coding RNA genes (~8x number of protein-coding genes)

In Craig Venter (one of the 1st people sequenced):

~3,000,000 single nucleotides polymorphisms (SNPs)

14,779 SNPs in protein coding genes

 

50% of Russians in particular regions 50% of people have homozygous for deletion of particular genes (Glutathione, etc.)

On average, we have 60-70 different mutations all inherited from our parents.

One study of the genomics of a four-person family produces 20 terabytes of data. The problem lies in analysing the variation in the genomes.

Allele frequencies in a population achieve equilibrium randomly.

AA= Wild type homozygous. Aa=Heterozygous aa= Homozygous mutants.

Do Genes Affect Human Behaviour?

About 1/1000 males carry an extra Y-chromosome. 7/197 prison inmates have an extra Y-chromosome.

Risk factor and determinants are different.

Are genes determinants? For the XYY predisposition to violent behaviour, it can be.

Epigenetic Inheritance:

Epigenetic inheritance is a trait mappable to a locus, but does not involve a change in the DNA sequence at that locus.In other words, epigenetic genetics is a study of heritable changes in gene expression that do not result from a nucleotide sequence change.

DNA Methylation: (In humans) 1 kind of epigenetic mechanism, important for the normal development of higher organisms. It involves [WIKI] “…involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring (cytosine and adenine are two of the four bases of DNA). This modification can be inherited through cell division…’

2 class of DNA Methylation:

•  De novo: Establish new patterns of methylation. Methylates  DNA on unmethylated substrates
• Maintenance: Only methylates previously methylated DNA.

In humans, all sites of DNA methylation occur where   Cytosine is followed by Guanine, the CpG or GpC  (Its other parallel strand)  dinucleotide. At DNA replication, one goes to the two resulting chromatids, the new DNA is synthesised in the unmethylated form.

Methylation puts new information in the genome. A methylation process can block the regulatory proteins’ ability to bind to a particular methylatable site (upon methylation)

Methalone: The pattern of DNA methylation across the genome. Experiences can “write” heritable changes into the genome.

 

X Chromosome Dosage Compensation (Men and Women):

Anyone who has a smidgen of extra DNA or missing a part of a chromosome results in mental retardation.

X dosage differs between men and women in different species.

Mammals inactivate one of the two-X chromosomes in females. Happens at 1,000 cell stage. On inactive X-chromosome in women, there is a locus called the X-activation center, which acts in Cis to turn off the X-chromosome. The XIST gene at this location is transcribed at a high level from the inactive X. The RNA from this coats the entire X-chromosome, keeps all other genes off this chromosome. Interesting, at the XIC  center on active X-chromosome, there is a RNA called Tsix which goes across the XIC transcribing the opposite strand.

Biology 1a Lecture 24 Notes

Overview

More coffee.  More plugging how awesome UC Berkeley is.  Today is a 50 minute lecture on eukaryotic gene expression.  They are very ambitious in these classes.  Don’t feel bad if you don’t get everything.  Most students won’t get 100% in this class.  It takes awhile to sink in.

Details

Let’s review briefly.  EIOZYA is the lac operon.  Operators and promoters are close.  The operator is inhibited by the repressor.  Transcription factors bind to the promoter.

DNA is not a linear molecule.  It is folded up, some parts are close, others are far.  Most of the time, DNA is wound around histones.  Being able to open up and hide away the genome is what gene expression is all about.  It’s the transition from a static linear picture to a dynamic, non-linear one.

This is also called epigenetics.  Epigenetic changes are any changes to the genomic structure, not changes to the DNA sequence.  Epigenetic changes may also be passed on.

GE = Gene Expression

GE has three main ideas: huge complexes, large distances, and chromatin structure modification.

Transcription factors bind to the TATA box of the promoter.

Reporter gene is just a gene that makes a very easy to identify gene product.

Enhancers are modulatory regulatory elements.   That means they are like legos and come in pieces.  They may be upstream or downstream and may be very far away.  They increase production of the gene they bind to.

Nucleosomes are the structural and functional units of eukaryotic chromosomes.  Made of eight subunits called histones.  Histones are like beads on a string.  DNA is wound around them.  Each histone is 30 nm apart.  You can wrap 147 bp worth of DNA around a histone in one loop.

Histone code hypthesis: histone variance and modifaction controls the activity of a gene.  Histone modifications include: Acetylation, methylation, ubiquitinated, phosphorlyated.

Acetylation     Normally on, increases GE.  If off, decreases GE.

Methylation   Turn off increases GE, Turn on lower GE.

C. elegans is a slick creature.  It always makes 959 cells and the entire development is known.  We know almost everything about this organism.  72 cells have aptosis or a suicide order.  Imagine knowing what every human cell did in the body.

Review

Cochlea: scala vmt vestibuli, media, tymponi

Extraoccular Innervation: 3,4,6

Tissues: connective, muscular, nervous, epithelial

Rods for dark, cones for light

Fovea contains 35K cones

Taste: sour, salty, sweet, bitter

G = H -TS

PV = nRT

K = products/reactants

Brain: diencephalon, cerebrum, cerebellum, brainstem

Brainstem: midbrain, pons, medulla oblongata

SNS = fight or flight PNS = rest of digest