Genetics Flashcards
Mitosis stages
Prophase
Metaphase
Anaphase
Telophase
Prophase of mitosis
condensation of chromatic to discrete chromosomes
breakdown of nuclear envelope and formation of spindles at cellular poles
metaphase of mitosis
alignment of chromosomes at metaphase plate in middle - equatorial alignmnet
anaphase of mitosis
separation of paired chromosomes followed by migration to opposite ends of the cell
separation preserves the chromosomal umber in the daughter cells
telophase of mitosis
chromosomes are backed into distinct new nuclei in the emerging daughter cells
cytokinesis (division of cytoplasm) also starts at this time
mieosis
meiosis I and meiosis II
produces 4 daughter cells, either with half the number of parent chromosomes
how many chromosomes in human cell
46
(23 from each patent)
how many autosomes in human cell
22 pairs of autosomes
2 sex chromosomes
metacentric chromosome
centromere in the middle
p and q arms equal
acrocentric / submetcentric chromosome
p and q arms not equal
centromere closer to one end
telocentric chromosome
centromere at the tail of a chromosome
not seen in humans
holocentric chromosome
entire length of the chromosome acts as the centromere
not seen in humans
non-disjunction
failure of chromosome or chromatids to separate in meiosis, with one gamete receiving 2 copies of that chromosome and another with no copies
Down’s syndrome
Trisomy 21
1:700 births
reduced materal AFP, increased betaHCG, increased nuchal fold thickness on USS
95% due to meiotic non-disjunction
5% robertsonian translocation
1% mosaicism
Edwards syndrome
trisomy 18
severe mental retardation, rocker bottom feet, low set ears, micrognathia, congential heart disease, clenched hands, prominent occiput
1:8000
often death within 1 year of birth
F>M 3:1
Patau syndrome
Trisomy 13, 1:6000
severe mental retardation
microphthalmia
microcephaly
cleft lip/palate
coloboma eye
abnormal forebrain structures
polydactyly
congenital heart disease
Metafemale
trisomy X
Turners syndrome
80% from paternal X ch
1:2000 females
low hairline, broad chest, retronathism, webbed neck
Klinefelters
47 XXY
how many amino acids
20
how many possible codon combinations in genetic code
64
base pairs
AT
GC
DNA replication
production of new DNA copies from template DNA
Transcription
synthesis of RNA from nuclear DNA
takes place in cell nucleus
introns
junk sequences - do not code for anything
splicing
removal of introns
results in mRNA
translation
production of proteins from RNA
takes place in the cytoplasm
aided by ribosomes
exons
coding
point mutation
single base alteration in DNA
usually substitutions
could also be transition or transversion
frame shift mutations
deletion or insertion not in multiples of 3 codons
leads to shift in triplet reading frame with variable results
silent mutation
no change in protein product
mis-sense mutation
new mutant codon specifies a different AA with variable effects on final protein product
non-sense mutation
new codon is a stop codon
UUA UGA UAG
results in non functional protein
translocation
exchange of chunks of genetic materials from one chromosome to another
mutations occurring at ‘larger’ dimensions
reciprocal translocaiton
one segment exchanged for another segment among chromosomes
robertsonian transloation
non-reciprocal
results in single fused chromosome from 2 acrocentric non homologous chromosomes
small p arms are discarded, and metacentric fusion chromosomes results - single ch from the 2
only trivial loss of information
viable and ‘balanced’ within the individual
unbalanced translocation / monosomy
when gametes are formed, only one of the 2 gametes can have the whole translocated metacentric fusion chromosome
DiGeorge / velocardiofacial
22q11.2 autosomal dominant
deletion
mild-mod LD
facial deformities
cleft palate
malformed parathyroids - hypocalcaemia
broad nasal bridge
speech and swallowing problems
>25% have psychosis
Williams syndrome
7q11 microdeletion
hypercalcaemia at birth
supra valvular aortic stenosis
moderate LD
disinhibited disposition
speech artificially fluent
hyperacusis
Smith Magenis Syndrome
17p11.2 microdeletion
mod-severe LD
self harming behaviour
sleep disturbance
self hugging
angelman syndrome
15q11-13 deletion
maternally inherited
developmental delay, low IQ, jerky movement eg hand flapping
frequent smiling
seizures
prader willi syndrome
15q11-13 deletion
paternally inherited
obesity, short stature, small libs, decreased IQ, hyperphagia and skin picking
cri-du-chat syndrome
chromosome 5p deletion
feeding problems
cat like cry
poorly developed facial features
mendelian laws of inheritance
uniformity
segregation
independent assortment
law of uniformity
DD x dd = Dd
two alternative alleles at one locus
two homozygous parents
all offspring are of uniform type
law of segregation
Dd x Dx = DD / Dd Dd / dd
two heterozygous parents
three possible types of offspring
law of independent assortment
DdHh (blue eyes brown hair) x ddhh (brown eye, black hair) = DdHh / ddHh / Ddhh / ddhh
two loci with alleles D d H h
double heterozygote x double homozygote parent
4 possible types of offspring, each with equal probability
incomplete penetrance
if patient have dominant disorder but does not manifest clinically
gives appearance of gene skipping a generation
tuberous sclerosis
9q34 / 16p13
autosomal dominant
1:30,000
adenoma sebaceum, normal to severe MR, ash leaf macules, brain hamartomas, heart and kidney cysts
treacher collins syndrome
5q31
autosomal dominant
1:40,000
maxilla mandibular hypoplasia
malformed pinna
down slanting palpebrae
mild to mod MR
apert syndrome
10q
autosomal dominant
variable MR
cranio syntosis
shallow orbits
trapezoid mouth
mitten hands and feet
noonan syndrome
Chr 12
autosomal dominant
1: 1500
mild MR
short stature
nuchal oedema/webbed neck
pulmonary stenosis
cryptorchidism
hurler syndrome
4p16
autosomal recessive
1:100,000
deteriorating IQ after age 2
coarse facies
clouded cornea
joint stiffness
lesch-nyhan syndrome
Xq 26-27
x linked recessive
deficiency of enzyme HGPRT
poor muscle control
moderate mental retardation
self mutilating behaviour - biting
hyperuricaemia
hyperuricosuria
severe gout and kidney problems
mitochondrial inheritance
maternally inherited
MELAS
LHON (levers hereditary optic neuropathy)
anticipation
disease develops earlier in successive generations
fragile X syndrome trinucleotide repeat
CGG
friedreich ataxia trinucleotide repeat
GAA
huntington chorea trinucleotide repeat
CAGmyo
tonic dystrophy trinucleotide repeat
CTG
fragile X syndrome
males>female 2:1
trinucleotide repeat expansion CGG
anticipation seen
reduced IQ
enlarged testes
prominent ears
protracting jaw
high pitched voice
southern blotting
detection of specific sequence of DNA
western blotting
detection of specific protein after electrophoresis
northern blotting
detection of specific RNA after electrophoresis
PCR
minute amount of DNA can be amplified
between two oligonucleotide primers
denatured with heat then annealed
FISH
detect and localise specific DNA sequences on chromosomes
isolated and inserted into plasmids which are vectors
concordance
a twin pair is concordant when both co twins have the same disease expression
discordant if one has the disease and the other doesnt
heritability
main measure of genetic variation in polygenic traits
the proportion that is genetic, not environmental
the relative influence of genetic factors in defining the variance in a trait
schizophrenia heritability
80
bipolar heritability
> 80
major depression heritability
40
generalised anxiety heritability
30
panic disorder heritability
40
phobia heritability
35
alcohol dependence heritability
60
big 4 personality traits in order of heritability
OECNA
openness - 57%
extraversion - 54%
conscientiousness - 49%
neuroticism - 48%
agreeableness - 42%
hardy weinberg principle
in the absence of mutation, non-random mating, selection and genetic drift, the genetic constitution of the population remains the same from one generation to the next
when does hardy weinberg equilibrium not hold true
natural selection
genetic drift
gene flow
consanguinity
high frequency of mutations
genetic drift
gene frequency change caused by limitations in population size
gene flow
exchange of genes between populations
due to migration or other social reasons, populations are not ‘closed’
consanguinity
non-random mating occurs, and mutations are preserved within a closed pedigree
autosomal recessive diseases are more often seen in consanguinous families
epistasis
gene-gene interactions between different alleles at different genes
locus heterogeneity
when same diseases phenotype can be caused by mutations in different loci
allelic heterogeneity
same disease phenotype resulting from different types of mutations at the same loci
pleiotropy
when a single disease-causing mutation affects multiple organ systems
monozygotic twins
identical twins
when embryo is cleared during early development
dizygotic twins
fraternal twins
share 50% of genes
two ova two sperm
pairwise concordance
number of twin pairs who both have the disorder divided by total number of pairs
probandwise concordance
number of affected twins divided by total number of co-twins
LOD score showing statistical evidence of linkage
> 3
LOD as evidence that two loci not linked
-2 or less
schizophrenia genes
NRG1
DTNBP1
G72
DAAO
RGS4
COMT
DISC1
dysbindin
bipolar disorder genes
BDNF
DAO G72/G30
COMT
alzheimers genetics
APP (Ch 21)
presenilin 1 (Ch 14)
presenilin 2 (Ch 1)
APOE
CADASIL
form of amyloid angiopathy that can present with alzheimers like features
NOTCH3 is associated gene
19p13.1-13.2
frontotemporal dementia genetics
progranulin gene (PGRN)
chromosome 17q21
parkinsons disease genes
PARK1, PARK4 - 4q21 alpha synuclein
PARK2 6q25 parkin gene
PARK8 12 cen LRRK2 gene
PARK6 1p35-57 PINK1 mitochondria
PARK7 1p38 DJ-1
autism sibling rate
2-8%
50x relative risk in siblings
autism monozygotic concordance
60%
autism dizygotic concordance
0%
ADHD first degree relatives risk
15-60%
2-6 relative risk
ADHD second degree relatives risk
3-9%
0.5-0.8 relative risk
ADHD heritability
70-80%
antisocial personality disorder heritability
60-70%
panic disorder lifetime prevalence
4.7%
approaches used in genetic clinics for genetic testing
direct testing - sample tested for certain genotype
gene tracking - many family members tested to see whether patient has inherited high risk Ch from heterozygous parent. can be used if the exact genetic locus associated with a disease is unknown
