Genetics Flashcards
APOE = late onset Alzheimer’s
Chromosome 19
APOE 2 = protective
3 = neutral
4 = increased risk
Early Onset AD
APP = chromosome 21. 10-15%
PSEN-1 = chromosome 14 30-70%
PSEN-2 = chromosme 1, 5%
CYP450 enzyme encoded by CYP2D6
Encodes debrisquine hydroxylase
Polymorphic, inactive 6% white people.
These people are then more prone to side effects from medication requiring CYP2D6 metabolism and are poor metabolism.
Many antidepressants are metabolised by CYP2D6
Missense mutation
A new nucleotide alters the codon producing an altered amino acid in the protein
Nonsense mutation
New nucleotide creates a STOP codon (TAA, TAG or TGA).
Point mutation
Simple change in one base of the gene sequence
Frame-shift mutation
An insertion or deletion of several nucleotides that shifts the sequence resulting in a different translation than the original
Silent mutation
Codes for the same amino acid
Copy Number Variants
Portions of DNA that vary in number
Associated with autism, schizophrenia and LD
Schizophrenia candidate genes
DTNBP1 = Dysbindin = chromosome 6 (p 22.3)
COMT = chromosome 22
DISC-1 chromosome 1
NRG1= Neuregulin-1 = chromosome 8 (p21-22)
COMT
Catechol-O-Methyltransferase
Role in dopamine metabolism in the prefrontal cortex. Degradation of catecholamines, especially clearing dopamine for synapse.
Low COMT = schizophrenia and OCD
Strongest candidate gene
Neuregulin (chr 8)
Growth factor stimulating neuronal development and differentiation.
Increased signalling in schizophrenia, suppress NMDA receptor and lower glutamate .
Dysbindin
DTNBP1 6
Distributed in muscle and brain tissue; production of lysosome organelles.
Decreased in schizophrenia
DISC1
Disrupted in schizophrenia; encodes multifunctional protein influencing neuronal development and adult brain function
MAPT
Tau, chromosome 17
Tau is involved in making and stabilising microtubules which help to maintain cell shape, are needed in cell division and to transport materials
APP
Amyloid precursor protein
Chromosome 21; y-secretase breaks down APP to soluble amyloid precursor protein and amyloid beta protein
Recombination fraction
Measure of distance between loci on a chromosome.
0% = very close
50% = different chromosomes
Closer two loci are on a chromosome, less likely they will be separated by crossing over
Transmission
Vertical = autosomal dominant
Horizontal = autosomal recessive
Kinght’s move = X-linked
Autosomal Dominant
Huntington’s Disease, neurofibromatosis type 1 and 2, tuberous sclerosis, achondroplasia, Noonan’s
Autosomal Recessive
Cystic fibrosis, homocytinuria, Wilson’s, PKU, Hurler’s, Tay-sachs
Mitochondiral
Levers hereditary optic neuropathy, kearns-sayre syndrome
X-linked dominant
Rett syndrome, vitamin d resistant ricketts
X-linked recessive
Lesch-nyhan, hunter’s , cerebellar ataxia
RNA
Single stranded
Ribose, phosphate and nitrogenous base
Shorter than DNA
Uracil
Transcription
Gene from DNA
RNA polymerase binds to the promoter region and prises dsDNA apart.
Template = antisense strand
Elongation = mrna synthesise from 3’-5’
RNA polymerase zips DNA as it works
At end of process, RNA detaches. Now have mRNA.
mRNA leaves nucleus and finds a ribosome in the cytoplasm.
Translation
Occurs in the Ribosome
mRNA = code for a specific protein
64 codons from reading frame
AAG, UUC
Each codon has an anti-codon, tRNA and each tRNA is attached to a specific amino acid.
AUG START Codon (Methionine)
UAA, UAG, UGA Stop Codon
Initiator tRNA + mRNA and small ribosome subunit. Large subunit then joins.
When next tRNA joins, 2 amino acid joins and then 1st tRNA leaves
Halpotype
Blocks of alleles transmitted as a block through pedigree
