MOLECULAR GENETICS Flashcards
Cell cycle
G0, G1, S, G2 = interphase
M -
G1 - growth
S phase - synthetic 46 chromosomes duplicated to chromatids
G2 phase - growth 2
M phase - mitosis
G0 –> cycle starts again (liver, neurones remain G0 indefinitly)
MITOSIS
Interphase
Prophase
Metaphase
Anaphase
Telophase
Interphase - period of growth
Prophase- Condensation of chromatin to discrete chromosomes + breakdown nuclear envelop - spindles opposite poles
Metaphase - Alignment of chromosomes at the metaphase plate (equator)
Anaphase- Separation of sister chromatids- migrate to opposite sides
Telophase- the chromosomes are packed into distinct new nuclei in the emerging
daughter cells. Cytokinesis (division of cytoplasm) also starts at this time
MEIOTIC DIVISION
Meiosis is divided into meiosis I and meiosis II
Meiosis 1- Meiosis 1 is a reduction division- occurrence of synapsis (crossing over) in the prolonged prophase phase
and non-separation of sister chromatids during anaphase 1 –> half chromosomal
numbers in daughter cells
Meiosis 2 is same as a normal mitosis.
Trisomies
21-
18-
13-
45X
XXY
21- Downs syndrome - meiotic nondisjunction of
homologous chromosomes.
18- Edwards- rocker bottom
13- Patau, microcephaly, polydactyly,
45X - Turners
XXY- kleinfelter
Chain termination signaled by
Posttranslaitonal modifications?
- take place?
UAA, UGA or UAG
post translational modifications take place in endoplasmic reticulum and golgi bodies.
Di-George (velocardiofacial)
Cri-du-chat
Di George- A. Dominant. >25% have psychosis. 22q11.2
Cri-du-chat- deletion chromosome 5P Feeding problems, cat like cry, poorly developed facial features.
(I’ll give you 5P to stop crying like a cat)
Williams syndrome
Smith Magenis
Williams syndrome, 7q 11 micro deletion hypecalcaemia t birth, LD (SMILEY PERSON)
Smith Magenis- LD, self harming behaviours, self hugging.
Angelmans syndrome
Prada Willi
Angelman’s syndrome- deletion 15q11-13- MATERNALLY INHERITED, low IQ, smiling, seizures.
Prada Willi- 15q11-13- PATRTNALLY INHERITED
obesity, short stature, decreased IQ
X carries more genetic material than Y, so women have X inactivation
When X chromosome is inactivated = visualized under the microscope as = highly condensed Barr body in the nuclei of interphase cells
e.g. trisomy X has 2 barr bodies
X activation occurs by DNA methylation
LYONISATION
mitochondrial inherited diseases
MELAS - mitochondrial myopathy, encephalopathy, lactic acidosis, recurrent, stroke syndrome .
Lebers Hereditary Optic Neuropathy - blindness more common in men
Fragile X (m>f)
where?
syx?
expansion of a tri-nucleotide repeat (CGG) proximal to FMR1 gene (200+ = syx)
- large testes, high voice, big ears, mental retardation
anticipation rates higher in maternal tri-nucelotide expansion occurs in oogenesis
Huntingtons
HD- Autosomal dominant - full penetrance, CAG repeat + 40-55, in father transmission, earlier onset
CHROMOSOME 4
(HD = D = 4 IN ALPHABET)
Cause of genomic imprinting?
DNA methylation effects.
POLYMORPHISM
(+1%) POPULATION AND not disease causing e.g ABO blood groups
Polymerase chain reaction
- double stranded DNA is denatured by heat into single strands
- reaction cooled for DNA annealing, primers bind
3 DNA polymerase used to extend primers - cycling to amplify
Linkage analysis
(based on the idea that genes that are close together on a chromosome are more likely to be inherited together - linkage disequilibrium)
Recombination frequency
provides a measure of the genetic distance between any pair of linked loci.
(LOD = log of odds) = LOD score over 3 = statistical evidence of linkage (-2) = not linked
?Most appropriate method
Is the phenotype familial?
What is the relative contribution of
genetic and environmental factors?
What is the mode of transmission?
Where might be the ‘culprit’ genes?
What are the actual genes responsible?
Is the phenotype familial? -Family study
Heritability - Twin studies, adoption studies
What is the mode of transmission? Segregation analysis
Where might be the ‘culprit’ genes? Linkage analysis
What are the actual genes responsible? Association analysis (population level)
Genetics of schizophrenia
genes suspected
Monozygotic - 48%
Dizygotic = 28%
higher concordance in hebephrenic and earlier age of onset
genes- NRG1- neuregulin, COMT
Genetics of mood disorders
bipolar
genes suspected in bipolar
One parent has a mood disorder = child has risk 10- 25 percent for mood disorder.
If both parents are affected - 50%
bipolar - monozygotic risk 40-70%, unipolar 25%
genes-
CACNA1C
BDNF - brain-derived neurotrophic factor,
- COMT
low activity allele may be associated with rapid cycling
Schizoaffective disorder
The risk to first-degree relatives for ANY psychiatric disorder is higher in SA disorder than any other psychiatric disorder.
Genetics of dementias
gene highest risk AD?
FTD
LBD
mutation in amyloid precursor protein and presenillin (Chr 21) and presenillin 1 (chr 14) 50% familial cases in pre-senile (under 60)
–> gene highest risk - APOLIPOPROTEIN E
FTD- some show tau proteins (17q21)
Tau negative = identifie in progranulin gene (also 17q21)
Genetics of alcoholism
Genetic risk higher in men
aDH4 - associated with early onset regular drinking
Variants GABRA 2 - associated with alcohol dependence.
OCD
Early onset suggests higher genetic risk
for family members
Risk to 1st degree relatives:
* Onset before age 18: range of ~10-35%
* Onset after age 18: no increased risk to ~15%
alzheimers genes
EOFAD - early onset familial alziemers disease (0.1% disease is EO)
amyloid precursor protein (APP) - (chromosome 21 so downs synd increased risk) accounts for 10-15% of EOFAD
presenilin one (PSEN-1) - accounts for 30-70% of EOFAD
- chromosome 14
presenilin two (PSEN-2) - accounts for 5% of EOFAD (PSEN 1)
APO E = 19 (91) (turn around numbers for old age v common)
APOE4 homozygote greastest risk
Most striking finding in huntingtons?
neuronal loss and gliosis in the striatum, particularly in the caudate nucleus, putamen and globus pallidus.
The most striking neuropathological feature of HD = atrophy of the head of the caudate nucleus.
exons
introns
translaiton occurs in the?
what bases join DNA/RNA
exons = expressed = code for things
introns- non coding
translation occurs in the ribosomes
NON COVALENT hydrogen bonds
Hardy Weinberg equaiton
P^2 + 2pq + q^2 = 1
% RISK OF OF developing schizophrenia if parent has the disorder?
12% risk of child developing disorder
identical twin 30-50%
80% heritability
22qDs
22% of people with this have schizphrenia / schizoaffective disorder. gvvv
Fragile X type inheritance
Rett syndrome type inherited?
Fragile X- X linked recessive
Rett- X linked dominant
A heritability of 0.50 indicates that 50% of the variation in a trait across the population ca
that 50% of the variation in a trait across the population can be explained by genetic differences
(not that half of an individual’s traits are genetic)
DISC 1 GENE
- Disrupted in schizophrenia 1 (DISC1)
- located on chromosome 1 that codes for a multifunctional protein.
- plays a crucial role in multiple aspects of brain development and function, including neurite architecture, neuronal migration, intracellular transport and synaptic transmission
- been associated with major mental illnesses such as schizophrenia, bipolar disorder and depression.
Copy number variations (CNV) have been most associated with which of the following conditions
autism spectrum disorder (ASD)
Di George
22 Di George street / 22 jump street
(roddy watched lots at uni with george)
