developmental genetics Flashcards
1
Q
when does gastrulation occur
A
14-28 days
2
Q
what is gastrulation
A
rearrangement of a single layer into a trilaminar structure
3
Q
trilaminar structure of gastrulation?
A
ectoderm, mesoderm, and endoderm
4
Q
what major structural feature forms in the gastrulation phase
A
primitive streak
5
Q
neurlation?
A
folding process that turns the nueral plate into the neural tube
6
Q
what type of birth defects does neurlation cause
A
neural tube defects
7
Q
where does neurulation close at
A
5 diff sites
8
Q
what does the ectoderm separate into during neurlation
A
neural tube, epidermis, and neural crest cells
9
Q
when is the mesoderm formed
A
gastrulation
10
Q
what does the notochord do?
A
induce neural tube and body axis
11
Q
what does the dorsal mesoderm give rise to?
A
axial skeleton, skeletal muscle, and CT
12
Q
what does the intermediate mesoderm give rise to?
A
kidneys and GU
13
Q
what does the lateral mesoderm give rise to?
A
heart, viscera, body wall
14
Q
what does the mesoderm consist of
A
notochord, dorsal mesoderm, intermediate mesoderm, lateral mesoderm, and head mesenchyme
15
Q
what layer of the trilamina causes many birth defects
A
mesoderm
16
Q
what does the endoderm form
A
lining of digestive tract, respiratory tree, middle ear, thymus, thyroid, and parathyroids
17
Q
purpose of primitive streak
A
crate A/P axis
18
Q
what does nodal expression do
A
initiates and maintains primitive streak
19
Q
purpose of Hox genes
A
position cells and tissues
20
Q
mutations in Hox genes leads to…
A
abnormalities of limb formation
21
Q
what is situs solitus
A
normal axis formation
22
Q
what is situs inversus
A
body is a mirror image- appendix on left side
23
Q
what is situs ambiguous/heterotaxy
A
same on both sides ex: left and right lung both have 3 lobes
24
Q
what is craniofacial development regulated by
A
Hox genes
25
1st MC birth defects? 2nd MC birth defects?
heart then limb
26
what embryonic later is limb formation derived from
mesoderm
27
what influences distal progression of limb
apical ectodermal ridge
28
what does the Apical ectodermal ridge stimulate proliferation of
mesodermal cells
29
what does the zone of polarizing activity specify
anterior and posterior information
30
what is key for thumb/finger differentiation
zone of polarizing activity
31
what occurs in Holt Oram Syndrome
malformations in radial, thenar, and carpal bones, congenital heart disease, cardiac conduction disease
32
what side of the body is Holt Oram Syndrome more severe in
left
33
what type of congenital heart defects do ppl with Holt Oram Syndrome have
ASD and VSD
34
what can cardiac conduction disease progress to
complete heart block with or without atrial fibrillation
35
what gene is the mutation on in holt oram synd
TBX5
36
organ formation?
Common cells and tissues “collaborate” for a unified function
37
what is skeletal formation dependent upon
osteoblasts
38
what is skeletal formation regulated by
transcription factor RUNX2
39
what do RUNX2 mutations cause
cleidocranial dysostosis
40
clinical features of cleidocranial dysostosis
Open fontanelle, Hypertelorism, Absent clavicles
41
what do PAX 6 gene mutations cause
aniridia (no iris)
42
what do Pax 6 gene mutations cause
small eye
43
ectopic expression?
Can manipulate the gene to express in a different location
44
example of ectopic expression?
pax 6 mutations
45
what are malformation defects due to
Defects due to intrinsically abnormal development
46
how do malformations arise
genetic, teratogens, and fetal environment
47
examples of syndromes with malformations?
TAR syndrome
Fanconi anemia
Polydactyly
48
what are deformation defects due to
nondisruptive mechanical force, resulting in abnormal form or position; extrinsic factor
49
what causes deformations
Uterine constraint
| Malformation or disruption may contribute
50
how is the prognosis for deformations
good! spontaneous resolution and internal fixation
51
examples of syndromes with deformations?
plagiocephaly, metatarsus adductus (clubfeet)
52
when do deformations occur
Post-conception!
53
what is a disruption defect due to
disruptive mechanical force
54
is disruption genetic
no
55
what are the effects of disruption
lasting effects since tissue can’t grow back
56
examples of disruptions
amniotic bands
57
dysplasia?
Anomalous organization of cells or tissues
58
2 types of dysplasia?
localized and genralized
59
tell me about localized dysplasia
Severity depends on extent of involvement; genetic at cellular level
60
tell me about generalized dysplasia
Usually genetic, and heritable with variable expressivity
61
examples of dysplasias
skeletal dysplasias
62
what type of inheritance pattern are skeletal dysplasias
autosomal dominant; usually new mutations
63
what type of disorder is usually parinatal letal
skeletal dysplasias
64
when are skeletal dysplasias detectable
in utero
65
spine?
spondylo
66
epiphyseal?
ossification separated from shaft by epiphyseal cartilage
67
metaphyseal?
growth area between epiphyses and diaphyses
68
diaphyseal?
shaft
69
localized rhizomatic dysplasia?
humerus is shorter than forearm
| femur shorter than leg
70
localized mesomelic dysplasia?
radius/ulna or tibia/fibula are short
71
localized acromelic dysplasia?
hand/foot
72
localized micromelic dysplasia?
whole limb
73
what is Thanatophoric dysplasia
long trunk and very short curved limbs,flat ossification centers of the vertebral bodies, femora and other bones are very short and usually curved
74
what is achondroplasia
rhizometric shortening of long bones, trident hand shape, bowing bc of bone length discrepancy
75
most mutable position in genome
achondroplasia gene
76
natural history of achondroplasia
```
Normal intelligence
Motor delays (hypotonia, large head)
```
77
adult height of someone with achondroplasia
50 inches
78
complications of acholdroplasia
Otitis media (midface hypoplasia), Respiratory problems and apnea, Foramen magnum compression, Midface hypoplasia, Hydrocephalus
79
diff btwn achondroplasia and hypochondroplasia?
similar features of achondroplasia but less pronounced, diagnosed at later age, height 50-65 inches, inc incidence of learning probs and ID
80
mutations in thanatophoric dysplasia, acholdroplasia, and hypochondroplasia are in what gene
FGFR3
81
what determines if someone gets thanatophoric dysplasia, acholdroplasia, or hypochondroplasia
point mutation location within the gene
82
what are skeletal dysplasias AKA
fibroblast growth factors (FGF)
83
what are Craniosynostoses
Premature closure of the cranial sutures
84
name the different skeletal dysplasias
craniosynostoses, thanatophoric dysplasia, acholdroplasia, and hypochondroplasia
85
what are mutations from Craniosynostoses in
FGFR1, FGFR2, FGFR3, TWIST
86
what are the different paracrine signaling families
FGF, hedgehogs, Wingless (Wnt), transforming growth factor beta (TGRB)
87
pathway of sonic hedgehog
SHH activates PTCH
| active PTCH inhibits SMO
88
what is SHH invoolved in
axis formation
89
what do mutations in SHH cause
holoprosencephaly
90
clinical features of holoprosencephaly
Cyclopia
| Central maxillary incisor
91
Cyclopia?
lack of 2 brain hemispheres
92
what is Smith-Lemli-Opitz syndrome an abnormality in
cholesterol metabolism; Deficiency in 7-dehydrocholesterol (7DHC) reductase
93
clinical features of Smith-Lemli-Opitz syndrome
Small head and body size
Intellectual disability
Ambiguous genitalia
Y-shaped 2/3 toe syndactyly
94
clinical features of Gorlin syndrome/Nevoid basal cell carcinoma syndrome
Multiple basal cell carcinomas
Macrocephaly
Jaw keratocysts
95
what do mutations in PTCH cause
Gorlin syndrome/Nevoid basal cell carcinoma syndrome
96
what do mutations in GLI3 cause
Greig Cephalopolysyndactyly syndrome
97
clinical features of Greig Cephalopolysyndactyly syndrome
Preaxial polydactyly, Macrocephaly, Seizures, hydrocephalus, and intellectual disability in severe cases
98
clinical features of Rubinstein-Taybi syndrome
Broad and angulated thumbs and big toes, Postnatal small head and body size, Mod-severe intellectual disability
99
mutations in CREBBP cause what
Rubinstein-Taybi syndrome
100
what axis formation are wingess (wnt) responsible for
dorsal/ventral
101
what organs do wingless (wnt) form
brain, muscle, gonads, and kidneys
102
what disordesr are wingless (wnt) responsible for
disorders of limb structure and gonadal development
103
what are Transforming Growth Factor β (TGFBs) associated with formation of
bones
104
name some RAS opathies
noonan syndrome, LEOPARD syndrome, Costello syndrome, cardio-facio--cutaneous syndrome, NMF1
105
PTPN11 mutations are associated with what
noonan syndrome
106
common genetic form of short stature?
noonan syndrome
107
MC heart defect in noonan
pulmonic stenosis
108
features of noonan
short stature, congenital heart defects, undescended testicles, minor learning difficulties
109
mutations in PTPN11, also RAF1 and BRAF are associated with...
LEOPARD
110
LEOPARD?
```
Lentigines (freckles)
ECG abnormalities
Ocular hypertelorism
Pulmonic stenosis
Abnormal genitalia
Retardation of growth
Deafness, sensorineural
```
111
features of Cardiofaciocutaneous synd
CHD, sparse/curly hair, sparse/absent eyebrows, ID, risk for neoplasia (Acute lymphoblastic leukemia)
112
Mutations in BRAF, MAP2K1, MAP2K2, KRAS are assoc with what
Cardiofaciocutaneous
113
clinical features of Costello syndrome
```
Severe postnatal feeding difficulties
Short stature
Intellectual disability
Curly, sparse fine hair
Congenital heart disease
```
114
HRAS mutations are seen in what
costello synd
115
features of NMF1?
Café-au-lait (coffee with cream) spots
Benign nerve tumors called neurofibromas
Freckling in the inguinal (groin) or axillary (armpit) regions
Eye changes
Learning problems or intellectual disability
116
what happens to the symptoms of NMF over time
they get worse; progressive
117
inheritance pattern of NMF 1?
autosomal dominant
118
in order for a tumor suppressor gene to be mutated what needs to occur
both copies must be mutated
119
in order for a proto-oncogene to be mutated what needs to occur
only one copy must be mutated
120
what do protooncogenes do
encourage growth
121
with a germline mutation, what cells are mutated
ALL cells start out with a SINGLE hit
122
Knudson’s Two-Hit Hypothesis is genotypically _____ and phenotypically______
dominant, recessive
123
is variable expressitivity quantitative or qualitative
qualitative
124
is penetrance quantitative or qualitative
quantitative
125
variable expressitivity?
you have the symptoms but to what degree
126
penetrance?
do you have symptoms or not?
127
transcription factors
Regulate when and how much a gene is transcribed
128
what are many CT disorders caused by
EMP dysfunction
129
EMP disorder examples?
Marfan syndrome
Collagenopathies including Ehlers-Danlos syndrome
Williams syndrome
130
mutation in FBN1 causes what
marfan syndrome
131
marfan features
Tall, thin body
long limbs
retinal detachment
risk for aortic root dilation and/or dissection
132
trmt for marfan heart issues?
beta blockers, Losartan
