Topic 11 Clinical Genetics Flashcards
If genes have a low penetrance, what does this mean
small infleunce in determining disease susceptibility
Mendelian disorders are mutations in what genes
single genes
affecting proteins/receptors
In multifactorial genetic diseases, how many organ systems are affected
one organ system
if multiple organ systems are affected, what category of genetic disease is it
chromosomal disorder
if a choroid plexus cyst is found in the brain, what may this indicate
downs
microdeletion of
22q 11.2
DiGeorges Syndrome
DiGeorges syndrome 3 symptoms
small mouth
prominent nose
congenital heart defects
microdeletion
7q 11.23
Williams Beuren Syndrome
Wide mouth Upturned nose Long philtrum Flattened nasal bridge Heart defects
Williams Beuren Syndrome
lack of dystrophin and disorganisation of fibres
X-linked Duchenne muscular dystrophy
Name 4 autosomal dominant diseases
Adult polycystic kidneys dis
Huntingtons disease
Neurofibromatosis
polyposis coli
Name 4 autosomal recessive
CF
phenylketonuria
spinal muscular atrophy
congenitial adrenal hyperplasia
Leber Hereditary Optic Neuropathy
mitochondria mutation
what is the most common form of cancer
sporadic cancer
Sporadic cancer is inherited how?
inherited dominantly
Chorea is what?
What is it found in
Involuntary jerking / twitching
Huntingtons Disease
CAG trinucleotide repeated passed down from generation to generation leading to earlier onset on symptoms.
what is this phenomenon called
anticipation
in phenylketonuria, what is absent
Phenylalanine Hydroxylase (PAH)
Pegvaliaase (Palynziq) is a PEGylated phenylalanine ammonia lyase (PAL) designed for what
reducing phenylalanine in phenylketonuria
Alkaptonuria has what absent?
Homogentisate dioxygenase
Neonatal screening is done via what
Tandem mass spectrometry
the most common inherited metabolic disease
what sort of mutation is it
Familial Hypercholesteraemia
autosomal mutation in LDLR
Tendinous Xanthomas on hands / heels is a sign of what
FH
Xanthelasmata + Arcus Cornealis is a sign of what
FH
Tay Sachs Disease is a disorder of what
lysosomal storage disorder
Tay Sachs Disease what is absent
what does this lead to
Hexosaminadase A deficient
accumulation of GM2 in brain
death due to pneumonia
where is Tay Sachs Disease prevalent in
jewish population
in the G1 phase, what is duplicated and whats not
cellular contents duplicated
chromosomes not
in S phase, what is duplicated
chromosomes
46
What is done in the G2 phase
cell checks for errors
makes repairs
G0 phase
cell cycle arrest
Stages of cell division in order
Prophase
Metaphase
Anaphase
Telophase
“Chromatin condenses into chromosomes “
prophase
“Nuclear envelope disappears
Chromosomes align at equatorial plate”
Metaphase
“Sister chromatids separate
Centromeres divide”
Anaphase
“Chromatin expands
Cytoplasm divides”
Telophase
where does Chiasma form
meiosis
In G banding, what stain is used
Giesma
P arm is what
short arm
Light bands are rich in what?
they replicate early in what phase
GC rich (less condensed chromatin)
S phase
Dark bands are rich in what?
They replicate when
AT rich (condensed chromatin)
Replicates late
what phase is the only time when chromosomes are visible
metaphase
in trisomies, by how much is produced extra
1.5x
in deletions/monosomies how much is produced less
0.5x
Tetraploidy = how many chromosomes
92
in triploidy = how many chromsoomes
69
Name 5 numerical chromosome abnormalities
Edwards (tri18) Patau (tri13) Down (tri21) Turner (45x) Klinefelter (47XXY)
for every 16 days from puberty, what forms
4 spermatozoa form
2 Secondary spermacytes form what
4 spermatids
Marfan disease is what disorder?
What is the mutation rate relative to
CT disorder
relative to older age
Achondroplasia disease is what
What is the mutation rate relative to
Disproportionate dwarfism
relative to older age
22 mitotic cell division by 5 months of gestation produces how many oocytes
2,600,000 oocytes
how many polar bodies are formed in ovulation and fertilisation
2
in non disjunction in meiosis 1, what 2 type of cells are formed
2x Disomic gametes
2x Nullsomic gametes
in non disjunction in meiosis 2, what cells are formed
Disomic
Nullisomic
monosomic
2x normal
2x abnormal
what causes mosaicism
embryo undergoes abnormal seperation of chromosomes in one of its cells
normal fertilization
what does mosaicism lead to?
what affects the phenotypic expression of it
2 population of cells
depends on how early the non-disjunction event was
mosaicism is found in down syndrome…. what % parental origin is it?
92% paternal
mosaicism is found in Edwards syndrome…. what % parental origin is it?
90% maternal
clenched hands and overlapping fingers are found in what syndrome
Edwards Syndrome
Affects midline structures
Incomplete lobation of brain
Cleft lip
Congenital heart disease
are found in what syndrome
Patau syndrome
patau syndrome is what % parental origin
85% maternal
Infertility
Poor secondary characteristics
Tall
Gynecomastia
is found in what syndrome
what is its karotype
klinefelters syndrome
XXY
what parental origin is klinefelters syndrome
55% maternal
Short stature Primary amenorrhoea Congenital heart disease Low hairline / narrow hip development Hyperconvex nails
is found in what syndrome
what is its karotype
Turners Syndrome
45, x
in Robertsonian translocation, what happens
fusion of 2 chromosomes
from breaking of 2 acrocentric chromosomes close to centromeres
what chromosomes are found in robertsonian translocation
13 / 14 / 15 / 21 / 22
what is lost in robertsonian translocation?
what is fused
short arm lost
long arm fusion
breaking of 2 non-homologous chromosome is what sort of translocation?
reciprocal
Genetic change associated with neoplastic / cancer disease process is what
Acquired Cytogenetic abnormalities
Acquired Cytogenetic abnormalities example
Chromosome 9 –> 22
Philly gene (CML 90%)
In neoplasm follicular lymphoma, what is translocated?
Bcl-2 oncogene (18–>14)
what happens in neoplasm follicular lymphoma
Neoplastic proliferation of B-lymphocytes
as Bcl-2 gene is constantly activated which suppresses cell death
- BM
- Lymph nodes
- Solid tumours
- Chorionic Villi (CVS)
are contain what type of cells
Spontaneously proliferating cells
How many days culturing does blood lymphocytes need?
How many days culturing does amniotic fluid samples need?
3 days
10 days
name an example of heteroploidy
Neoplasm follicular lymphoma
FISH
Fluorescence in situ hybridization
FISH is done on what 2 cell division phases
metaphase
interphase
Comparative genome hybridization can show what
loss/gain of chromosomes regions
name the procedure of DNA PCR and temperatures
Denaturation (94)
Annealing of primers (55)
Primer extension (72)
Amplification (72)
Primers in PCR are what length?
15-30
optimum temperature for DNA polymerase is what
75*
what is used in the termination of a DNA strand
why is it used
ddTTTP
no 3’ hydroxyl group
cant form next phosphodiester bond
MEGF10 mutation is found in what
muscular dystrophy
In Oligonucleotide Ligation Assay (OLA), if ligation fails what does this indicate
Missmatch
point mutation
what results in point mutation
2 mutant alleles
