Week 3 Flashcards
How heritable is major depression?
Across studies h2 = 0.37
How do you diagnose major depression?
5 or more symptoms (e.g. Low mood, fatigue, suicidality, weight change, feelings of worthlessness)
That should include either
Low mood
Anhedonia (inability to feel pleasure)
And should last for at least 2 weeks
What is meiosis?
Meiosis is the process where haploid cells are created.
Example parent cell contains 2 pairs of chromosomes (a cell in your body contains chromosomes one from your mum and one from your dad) (prophase 1)
Prophase 1: Chromosomes duplicate
Meiosis 1 - basically chromosomes line up into tetrads, tetrads align at the metaphase plate (metaphase 1)
Crossing over means that each copy of the chromosome contains a mixture of DNA from mum and dad.
The tetrads or homologous chromosomes separate as the cells divide into daughter cells (meiosis 1)
These cells divide again into haploid daughter cells (meiosis 2) which contain a mixture of DNA material for each single chromosome.
What is mitosis?
Basically cell division. Diploid cells are created and they are exact copies of the original cell.
Prophase: Chromosomes are duplicated
Metaphase: Chromosomes align at the metaphase plate
Anaphase
Telophase: sister chromatids separate during anaphase and cells are reproduced.
What is linkage?
Linkage is he process by which during meiosis crossing over alleles that are closer together are more likely to be inherited together - they are linked
How do linkage studies work?
Neighbouring genes tend to stay together during meiosis and are therefore genetically linked
Affected and unaffected family members (pedigrees) can be mapped to identify regions of the genome containing disease-causing genes.
We can use genetic markers from just a few places throughout the genome to observe the co-segregation of these markers with disease to identify regions linked to a disorder.
When are linkage studies useful?
For Mendelian disorders (single genetic variant)
Not useful for complex disorders traits like depression or schizophrenia where there are 1000s of genetic variants.
What is an association study?
This is where for example you look at a group of cases and controls with a disease and you see if the cases have a higher number of a specific variant.
These can come in two types candidate gene studies (looking at a specific variants and phenotypes) or genome-wide (GWAS) looking across the genome
How to run a candidate gene association study step by step? (6 steps)
- Select a candidate gene
- Select a variant in that gene
- Get some samples and extract the DNA
- Genotype your variant
- Quality control your data
- Test for association
The monoamine hypothesis suggests that what neurotransmitters underpin depression?
Serotonin, noradrenaline, dopamine
What are three ways to extract DNA?
Whole blood (expensive, difficult to collect, ship and store, highest yield and good quality DNA)
Cheek swabs (very cheap, relatively stable, easy to collect, lower yield and lower quality of DNA)
Saliva (reasonably cheap, stable at room temp for 6-12 months, reasonably high yield and better quality DNA than cheek)
How do you extract DNA?
Lyse (break) cells To release DNA using lysis buffer and digest using proteinase k
Separate the DNA from protein and other components in the cell
Isolate concentrated DNA with isopropanol in the cell
What three ways can you genotype SNPs?
Primer extensions
Taqman
Whole genome arrays (microarrays)
How can you genotype variable number tandem repeats?
Polymerase chain reaction (PCR) And gel electrophoresis
When carrying out a PCR reaction what are the three steps for genotyping?
Denaturation (DNA is denatured at 95c)
Annealing (primers bind at 55c)
Extension (Taq extends the DNA at 72c)
Process is repeated 35 times
