Genetics Flashcards
where is the promotor located
5’ to a specific gene
RNA polymerase bdings
differences between southern
northern and western analysis
southern - DNA digested - labeled DNA probe
northern - RNA digested - labered DNA probe
western - protein probe
dot blot vs reverse dot blot
dot blot: DNA region amplified applied to membrane + probe of single mutation
reverse: allele specific NTs applied to membrane + denatured DNA; hydridization detected
FISH useful for
trisomy 13, 18, 21
Prader-willi/Angelman
criduchat
digeorge
miller dieker
williams
4p
comparative genomic hybridization
identify number of copies of gene to determine if gain or loss
microarray expression analysis
gene over or underexpressed
mutation microarray analysis
identify mutations or polymorphisms in gene
targeted mutation analysis
detect known sequence of triplet repeat expansion
robertsonian translocation
long arms of 2 different chromosomes fuse at centromere and very short arms are lost
can only happen with 13, 14, 15, 21 and 22
MCC robertsonian translocation
chr 21 and 14
Lyon hypothesis
inactive X forms barr body
AR song
alpha beta, PKU
iron, copper, bern-sou
Hartnup glanzmann fanconi
AR yes its true
21OH def, congenital muscular dystrophy
CF
IEM
AD song
von von ALS, Rb MEN
Tubes & spheres and &huntingtons
Marfan, Ehler’s Dan
NF1 and 2 don’t FAP too much
Autosomal Dominant yes this song is clutch
XLR
the OTC bitsy Hunter’s name was Lesch Fabry
he shot the Menke WASP and G6P
up came Bruton what a Douchey guy
A & B are XL dont forget DI
uniparental disomy
loss of function in a gene that requires 1 from each parent
prader willi and angelman due to 15q region
associated with AMA
klinefelter
trisomy 13, 18, 21
associated with advanced paternal age
achondroplasia
apert
crouzon
NF
OI
thanatophoric dysplasia
klinefelter/tri21
most cardiac lesions occur more in males aside from
ASD and PDA
recurrence risk cardiac defect
1 child –> 3-4%
2 children –> 10%
recurrence risk cleft lip
1 child and 1 unaffected parent - 4-5%
1 child and 1 affected parent - 10%
recurrence risk cleft palate
1 child - 2-6%
recurrence risk club foot
1 child - 2-5%
1 child and 1 parent - 25%
recurrence risk DDH
1 child - 3-4% (0.5% if M, 6% if F)
recurrence risk Hirshsprung
1 child 3-5%
recurrence risk NT defect
1 child 3-5 %
recurrence risk pyloric stenosis
1 mother- 19% son 7% daughter
1 father- 5.5% son 2.4% daughter
1 child - 3% (4% brother, 2.4% sister)
recurrence risk trisomy 21
mother with balanced translocation - 10-15%
father with balance translocation - 5%
prior child tri21; parents no translocation - 1%
Hardy Weinberg
p + q = 1
p^2 + 2pq + q^2 = 1
trisomy 8
camptodactyly
thick lips
deep eyes
cupped ears
hip dysplasia
MR
trisomy 13
80% from maternal origin
midline defects
VSD > PDA
cutis aplasia
narrow hyperconvex fingernails
cleft lip/palate
small eyes
umbilical/inguinal hernia
holoprosencephay
fetal HgB
increased neutrophils with nuclear projections
trisomy 18
95% of maternal origin
VSD, PDA
clenched hand
rocker bottom feet
small mouth
cryptorchidism
trisomy 21
MCC nondisjunction - maternal
75% born to those < 35 due to high reproductive rate
endocardial cushion defect
hypothyroid
hyperflexible
upslanting palpebral fissures
hypotonia improves with ages
cri du chat
del 5p paternal
hypertelorism
downward palpebral fisssues
MR
FTT cat like cry - abnormal laryngeal development
del 13q
thumb hypoplasia
retinoblastoma
coloboma
microcephaly
high nasal bridge
cryptorchidism
Wolf Hirshorn
del 4p 87% denovo
greek warrior helmet
broad beaked nose
hyperteleroism
low ears with preauricular dimble
microcephaly
seizures
Angelman
70% of deletion of 15q maternal origin
22q11.2; defect in what arches?
digeorge
defect in 4th branchial arch and derivatives of the 3rd and 4th pharyngeal pouch
AD
what is most common chromosome deletion?
22q11.2
prader- willi
75% deletion 15q11-13 of paternal origin
testing progression for angelman or prader willi
chromosomal - FISH - polymorphic genetic markers - imprinting center
Rubenstein-Taybi
16p13.3 - cAMP regulated enhancer binding protein
broad thumbs, broad first toe
downward slanting palpebral fissures
hypoplastic maxilla
narrow palate
beaked nose
hirsutism/synorphys
FTT
WAGR
wilms tumor
aniridia
genitourinary
retardation
11p13 del denovo
williams
7q11.23 del – elastin gene – sporadic
supravalvar subaortic stenosis > PPS
hypoplastic nails
prominent lips, hoarse voice
stellate iris
achondroplasia
80-90% de novo
AD FGFR3 gene
trident hands
depressed nasal bridge
megalocephaly
narrow spinal cord
normal IQ
apert vs crouzon
both = AD, FGFR2 mutations
Apert = midface hypoplasia, broad thumb and toe/syndactyly
irregular craniosynostosis
MR more common
Crouzon = maxillary hypoplasia, premature craniosynostosis - coronal/lamboid/sagittal
MR less common
Beckwith Wiedemann genetics
11p15.5 region
50% hypomethylation of centromeric imprinting center
10% mutation CKN1C
Beckwith Wiedemann symptoms
macroglossia
linear earlobe fissures
exophthalmos
macrosomia
organ hyperplasia
fetal adrenocortical cytomegaly
wilms and hepatoblastoma (monitor every 3 months abdominal US until age 7)
Marfan symptoms
dilated aorta (yearly echo, beta blockers to reduce risk, abx for dentist)
arachnodactyly
hyperextensibility
scoliosis
lens subluxed UP
Holt Oram genetics and symptom
AD
12q2
ASD; upper limb defects
Marfan genetics
AD
fibrillin 15q21.1
Noonan genetics
sporadic AD
12q22
Noonan symptoms
dysplastic PV
pectus
webbed neck
cryptorchidism
abnormal coagulopathy
OI inheritance and types
AD
type 1 collagen
types:
1, sclera blue, fractures, deaf, wormian bones in cranial sutures
2. sclera blue, fractures, short and broad long bones, still born/die early - respiratory failure
3. blue sclera that normalizes, fractures at birth, IUGR, deaf
4. normal/gray sclera, bone deformities, abnormal dentition
Stickler genetics and symptoms
AD
type II collagen COL2a
12q13.11-q13.2
flat facies
myopia
deaf
spondyloepiphyseal dysplasia
mitral valve prolapse
thanatophoric dysplasia
AD
FGFR3 (4p16.3); extracellular or intracellulary tyrosine kinase domain
type 1 - more common, curved long bones, flat vertebral bodies
type 2 - straight femoral, tall vertebral bodies, clover leaf skull
narrow thorax, short limbs
treacher collins
AD
TCOF1 chr 5; 1/2 branchial arch
lower eyelid coloboma
down palpebral fissures
mandibular hypoplasia
dysmorphic ears
malar hypoplasia
Conductive hearing loss
normal intelligence
waardenburg
AD
- AD PAX3 2q35 lateral displacement of medial canthi, deaf
- AD, microphthalmia gene 3p12.3-p14.1 normal canthi, deaf
- AD, upper limb defects
- AD/AR + Hirschsprung
pigmentary abnormalities: white forelock, partial albanism
Carpenter
AR
polydactyly
lateral displacement of inner canthus
brachycephaly
MR
FTT
Ellis van-Creveld
AR
short distal extremities
polydactyly
nail/teet
short
narrow thorax
normal IQ
Fanconi pancytopenia
AR
chromosomal breaks in lymphocytes and AF cells
hyperpigmentation
radial/thumb hypoplasia
pancytopenia
Meckel-Gruber
AR 17q21-q24
polydactyly
microophthalmia
occipital encephalocele
cystic kidneys
Smith Lemli Optiiz
AR
cholesterol synthesis defect –> low cholesterol and elevated 7dehydrocholesterol
2nd and 3rd toe syndactyly
anteverted nares
hypogenitalia
MR
FTT
high mortality
TAR
AR
thyrombocytopenia
absent radii bilateral
thumb present
ulnar abnormalities
40% mortality - hemorrhage
Fryns Syndrome
AR
CDH
hirshprung
duodenal atresia
neuro abnormalities
coarse facies
Fragile X
XL dominant 80% penetrance in males 30% in females
triple repeat of CGG > 60 repeats
long face and ears, large testes, MR, cluttered speech
hyperextensible fingers
Menkes
XLR
copper deficiency
twisted fractured hair - lose pigmentation at 6 weeks
pudgy face
progressive cerbral deterioration
seizures
wormian bones
fractures - lateral spur formation
early death in infancy
Klinefelter
47XYY
hypogonadism
gynecomastia - atrophy seminiferous tubules
behavioral difficulty
germ cell tumors
turner
45X
chromosome deleted is usually paternal
cubitus valgus
cystic hygroma
webbed neck
gonadal dysgenesis
horseshoe kidney
lymphedema
gonadoblastoma
Cornelia de Lange symptoms
micromelia
synorphys
thin down turning upper lip
long curly eyelashes
hypertonicity
microbrachycephaly
hirsuitism
low posterior hairline
CHARGE
mutation in chromodomain helicase DNA binding gene 7 (CHD7) chr 8q12 –> altered chromatin
AD
Coloboma
Heart
Atresia of choanae
Retarded growth
Genital hypoplasia
Ear
Cat-eye
chr 22 extra part
22q11 triplicate/quadruplicate (instead of deletion in digeorge)
TAPVR, persistent L SVC
down palpebral fissures
anal atresia + rectovestibular fistula
coloboma of iris
triploidy
69XXY
large placenta with hydatiform changes
IUGR
3rd and 4th syndactyly
Cornelia de Lange genetics
mutation in 1 of 3 cohesin genes
1. NIPBL 5p13
2. SMC1L1 - Xp11.22
3. SMC3 - 10q25
Mobius
sequence
6th and 7th palsy
4 types:
1. destruction of central brain nuclei
2. hypoplasia or absence of central brain nuclei
3. peripheral nerve
4. myopathy
expressionless facies
micrognathia
talipes equinovarus
Goldenhar
unknown
1st and 2nd branchial arch
VSD
deaf
normal IQ
hemivertebrae
midface hypoplasia
klippel feil
unknown, sporadic
defect of cervical vertebrae
short neck
low hairline
limited head movement
deaf
sprengel deformity
klippel trenaunay weber
unknown;sporadic
asymmetric limb hypertrophy
vascular lesions
poland sequence
unknown; sporadic
proximal subcalvian arterial disruption in utero > poorly developed distal limbs
dextrocardia
unilateral hypoplasia or absence of pectoralis muscle
rib anomalies
russell silver
sporadic; chr 7?
small triangular facies
short
asymmetry of skeleton
5th finger clinodactyly
excess head and upper trunk sweating
late closure of AF
VACTERL
vertebral
anorectal
cardiac (VSD > Tof, CoA)
TEf
renal
limb (U>L, radial > ulnar)
- hydrocephalus (aqueductal stenosis)
arachnodactyly
homocystinuria
marfan
camptodactyly
isolated
tri 8
cleft lip or palate
charge
digeorge
meckel gruber
pierre robin
smith lemli opitz
tri 13
clinodactyly
carpenter
cornelia de lange
del 13q
klinefelter
rubenstein taybi
trisomy 21
holt oram
prader willi
coloboma
cat eye - iris
charge - retina
del 13q
treacher collins - eyelid
tri 13 -iris
cystic hygroma
noonan
turner
del 13q
tri 13, 18, 21
ocular hypertelorism
apert
cat-eye
criduchat
crouzon
del 13q
digeorge
noonan
tri 8
turner
hypotelorism
holoprosencephay
meckel gruber
williams
trisomy 13
limb hypertrophy
beckwith
klippel tranauney weber
lips prominent
tri 8
wagr
williams
hypogenitalia
carpenter
klinefelter
prader willi
smith lemli opitz
macroglossia
beckwith
congenital hypothyroid
tri 21
micrognathia
pierre robin
cat eye
charge
cornelia de lange
del 13q
digeorge
marfan
meckel gruber
mobius
russel silver
smith lemli
tri 8 and 18
wagr
polydactyly
carpenter
ellis van creveld
isolated
meckel gruber
tri 13
vacterl
radial hypoplasia
fanconi
tar
vacterl
syndactyly
apert
carpenter
cornelia
isolated
poland
smith lemli
tri 21
vacterl
rhizomelia
short proximal long bones
achondroplasia
mesomelia
short distal long bones
mesomelic dysplasia
micromelia
short proximal and distal long bones
achondrogenesis
short rib polydactyly
diastrophic dysplasia
OI type II
acromelia
small hands or feet
ellis van creveld
talipes
foot deformity
varus
inward
valgus
outward
equinus
downward
calcaneus
upward with heel downward
metatarsus adductus
medial deviation of metatarsal bones
c shaped lateral border of foot
talipes equinovarus
club foot
higher in hispanics
inversion and adduction of forefoot + inversion of heel, equinus of ankle, internal rotation
calcaneovalgus
flexible down and out appearance of foot, extreme dorsiflexion
congenital vertical talus
- rocker bottom foot
lethal skeletal dysplasias
- achrondrogenesis type 2: collagen 2
- congenital hypophasphatasia severe type: tissue non specific alk phos
- OI type 2: collagen 1 or 2
- short rib dysplasia
–ellis van creveld; ellis van creveld genes 1 and 2
– Jeune = IFT gene - thanatophoric dysplasia = FGFR3
nonlethal skeletal dysplasias
- achondroplasia
- campomelic dysplasia
- chondrodysplasia punctate
- stickler
what supplement helps PKU
5-Hydroxytryptophan
what is deficient in PKU
tyrosine
Pfeiffer clinical findings
brachycephaly
maxillary hypoplasia
hypertelorism
prognathism
broad thumbs
great toes, and syndactyly in both hands of second and third digits
Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome
- XLD
- ipsilateral hypoplasia of the limbs, facial hemidysplasia, and hypoplasia of various organ systems
- unilateral erythematous scales with clear midline demarcation that tend to improve with age
- Stippled calcification of the epiphysis
Phocomelia
fully formed hands attached to his trunk at the shoulder and craniofacial defects
ESCO2 gene AR
Congenital myotonic dystrophy (CMD) genetics
- AD
- 3’ noncoding DMPK gene
- chr 19q13.3
- CTG repeat
- splicing of CUG binding protein (CUG-BP) and Musclebind-like protein (MBNL)
Smith Lemli Opitz enzyme defect
7-dehydrocholesterol reductase
Legius syndrome
AD; SPRED1 gene
similar to NF1 without other significant neurocutaneous findings has:
* cafe au lait
* axillary freckling
* macrocephaly
* learning disability
what is a contiguous gene disorder?
deletion or duplication that affects several genes lying in close proximity to each other
i.e. Angelman
transient neonatal diabetes mellitus genetics
imprinting defect chr 6`
genetic test to confirm uniparental disomy
Single nucleotide polymorphism microarray
lactate elevation in NEC causes:
L lactate from tissue hypoxia
D lactate from production by enteric bacteria
how many de novo single nucleotide variants does each person have?
average 74
MC imprinting disorder
Beckwith Wiedemann
Jeune a.w which other organs
renal disease
pancreatic and hepatic fibrosis
hirshprung
