Developmental Genetics Flashcards
intrinsic causes of abnormality
how a mutation present in the embryo influences the developmental programs of the embryo and fetus
extrinsic causes of abnormalities
how an external factor disrupts normal developmental programs (drugs or pressure on fetus)
anomaly
structural defect of any type
dysmorphology
study of congenital birth defects that alter the shape or form of one or more parts of the body
dysmorphic trait origins
malformation, dysplasia, deformation, disruption
malformation
poor formation of tissue
dyplasia
abnormal organization of cells in tissue
deformation
unusual forces acting on normal tissue
disruption
breakdown of normal tissue
malformations and dysplasias result from _
intrinsic abnormalities in one or more genetic/developmental programs
deformations and disruptions result from _
extrinsic factors
deformations are usually from _
mechanical forces
disruptions are usually from _
trauma, amniotic bands, teratogens
syndromes
anomalies due to intrinsic factors; patterns of primary malformations or defects with a single underlying cause
multiple anomalies occur in _
parallel
sequence
results from a single, localized, primary anomaly causing a cascade of subsequent defects
signaling molecules
turn off/on transcription factors
transcription factors
regulate cell genes involved in differentiation, proliferation, etc.
families of signaling molecules
TGF-beta, FGF, SHH, Wnt
families of transcription factors
HOX, PAX, SOX, WT1
morphogens work by _
secretion or cell-cell contact and follow concentration gradients
neural tube formation
notochord secretes SHH and ectoderm secretes TGF-beta –> gradient activates TFs in different zones, giving dorsal, ventral, and motor neuronal subtypes
What concentrates morphogens?
currents generated by cilia
HOX genes
play major role in anterior-posterior segmentation
HOX genes determine _
organs and limbs
morphogen gradients determine
developmental identity of somites
fetal alcohol syndrome
example of a disruption (extrinsic); ethanol interferes with normal growth in embryo
symptoms of FAS
small head, small eye openings, short nose, thin upper lip, flat midface, low nasal bridge
zone of polarizing activity
secrete SHH gradient in hand (starts at pinky region)
duplication of ZPA
will get more pinky and ring fingers where duplication is placed (mirror hand)
mutation in Wnt3 germline mutation
would cause failure to form all four limbs as a result of no apical ectodermal ridges forming
mutation in Wnt3 somation cells
would result in failure of the AER to form on that one limb bud, resulting in “amelia” of only that limb
digit formation follows a _
SHH gradient
What explains transverse limb defect affecting only one limb?
vascular accident occurs, decreasing arterial blood flow to developing field due to an embolism or other event causing severe hypoxia
transverse limb defect
one where proximal structures are intact but structures distal to transverse plane are partially or completely absent
failure of cilia current
situs invertus, heart is on opposite side
Proteus syndrome
dysregulated development resulting in somatic mosaicism
proteus syndrome cause
AKT1 (growth promoting protein) is irregularly expressed resulting in malformations of vascular system, connective tissue, and skeleton; original germline mutation with somatic mutations following
teratogens
agents that produce congenital malformations
major human teratogens
ethanol, inhalants, metals, prescription medications, maternal medical conditions
retinoic acid embryopathy
caused by accutane (isotretinoin)
fetal hydantoin syndrome
caused by mother taking dilantin
teratogens at 0-3 weeks
failure of implantation or death of embryo
teratogens during weeks 3-8
maximal sensitivity to abnormal development; malformation of embryo may occur
teratogens at weeks 8-38
functional disturbance of fetus (mental retardation)
prenatal cocaine exposure
alters brain chemistry (dopamine receptors), constriction of maternal/fetal blood vessels causing hypoxia, fetal strokes, premature labor
thalidomide
inhibits angiogenesis (new blood vessels) induced by betaFGF and VEGF; originally used to treat morning sickness
thalidomide embryopathy
results in severe limb abnormalities
retinoic acid embryopathy
results in craniofacial defects, CP, eye and ear malformations, CNS defects
maternal diabetes
as baby grows, it will try to cure the mother’s diabetes by producing insulin, causing baby to have extra glucose resulting in weight gain; can result in hypoglycemia (increased insulin taking glucose away from brain) which result in brain damage
maternal phenylketonuria
if mother does not adhere to strict diet, the baby can be exposed to high levels of phenylalanine causing low birth weight, slow growth, small head, heart disorders
TORCH
five infectious entities: toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex
toxoplasmosis
a parasite that is ingested in undercooked meat and by exposure to cat feces; infection can affect muscle and nerve (hydropcephalus, eye and ear problems
other agents
syphilis, HIV, zika, listeria monocytogenes, varicella; often causes microcephaly (undergrowth of brain)
rubella in mother
can cause eye anomalies, microcephalus, heart disease, petechiae
cytomegalovirus
similar effects to toxoplasmosis
herpes simplex
viral encephalitis, hydranancephaly, skin vesicles, and scarring
physical teratogen
radiation
