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1 gene has more than 1 effect on an individual's phenotype
pleiotropy
mutations at different loci can produce the same phenotype e.g. albinism
locus heterogeneity
MR, hyperphagia, obesity, hypogonadism, hypotonia
Prader-Willi syndrome deletion of nlly active paternal allele
MR, seizures, ataxia, happy puppet
Angelman's syndrome deletion of nlly active maternal allele
all female offspring of affected father are diseased
XD ex: hypophosphatemic rickets example:
AKPD chr
16 also have berry aneurysms, MVP, polycystic liver dz
hereditary hemorrhagic telangiectasia / Osler-Weber-Rendu syndrome
telangiectasia, recurrent epistaxis, skin discoloration, AVM AD
Name some AD dz
hereditary spherocytosis Marfan's MEN tuberous sclerosis VHL
deletion of tumor suppressor gene on chr 3
VHL constitutive expr of HIF (txn factor) and activation of angiogenic growth factors
deletion of tumor suppressor gene on chr 5
FAP deletion of APC
MR, large testes/jaw/ears, autism
fragile X syndrome CGG repeat mutation affecting methylation and expr of FMR1
CTG repeat
myotonic dystrophy
pregnancy quad screen for Downs
dec AFP inc A-inhibin dec estriol inc B-HCG
micrognathia (small jaw), clenched hands, low-set set ears, prominent occiput, congenital HD, severe MR, rocker-bottom feet
trisomy 18 - Edwards
holoProsencephaly, cleft lip/Palate, Polydactyly, severe MR, rocker-bottom feet, microphthalmia, microcephaly
trisomy 13 - Patau
microdeletion of 5q
cri-du-chat
microdeletion of 7p, which includes elastin gene
Williams elfin facies, MR, well-developed facial skills, cheerful disposition, cv problems
22q deletion syndromes
DiGeorge velocardialfacial syndrome due to aberrent development of 3rd and 4th branchial pouches
aortic arch 1
maxillary artery
aortic arch 2
stapedial and hyoid arteries
aortic arch 3
common carotid artery, proximal part of internal carotid
aortic arch 4
aortic arch proximal part of R subclavian artery
aortic arch 6
ductus arteriosus, proximal part of pulm arteries
mesencephalon
midbrain
metencephalon
pons, cerebellum
myelencephalon
medulla
associated with holopresencephaly
severe fetal alcohol syndrome, Patau's syndrome
branchial arch 1
CN V2 and V3 Meckel's cartilage: mandible, malleus, incus, sphenomandibular ligament muscles: muscles of mastication, mylohyoid, ant digastric, tensor tympani, tensor veli palatini, ant 2/3 of tongue
branchial arch 2
CN VII Reichert's cartilage: stapes, styloid process, less horn of hyoid, stylohyoid ligament muscles: facial expr, stapedius, stylohyoid, post digastric
branchial arch 3
CN IX cartilage: greater horn of hyoid muscle: stylopharngeus Congenital pharyngocutaneous fistula - persistence of cleft and pouch - fistula btwn tonillsar area, cleft in lateral neck
branchial arch 4
CN X, superior laryngeal branch (swallowing) cartilage: thyroid, cricoid, arytenoids, coriculate, cuneiform muscles: most pharyngeal constrictors, cricothyroid, levator veli palatini
1st arch neural crest fails to migrate
mandibular hypoplasia, facial abnls (Treacher-Collins syndrome)
branchial arch 6
CN X, recurrent laryngeal branch (speaking) cartilage: thyroid, cricoid, arytenoids, coriculate, cuneiform muscles: all intrinsic muscles of larynx EXCEPT cricothyroid
1st branchial cleft
ext auditory meatus
2nd-4th branchial clefts
temporary cerival sinuses, obliterated by proliferation of 2nd arch mesenchyme
1st branchial pouch
middle ear cavity eustachian tube mastoid air cells
2nd branchial pouch
epithelial lining of palatine tonsils
3rd branchial pouch
dorsal wings: inf parathyroids ventral wings: thymus "3rd pouch develops into 3 things"
4th branchial pouch
superior parathyoids
Fabry's disease
a-galactosidase A deficiency ceramide trihexoside accumulates
Gaucher's disease
most common b-glucocerebrosidase deficiency glucocerebroside accumulates
Niemann-Pick disease
sphingomyelinase deficiency sphingomyelin accumulates
Tay-Sachs disease
hexosaminidase A deficiency GM2 ganglioside accumulates
Krabbe's disease
galactocerebrosidase deficiency galactocerebroside accumulates
metachromatic leukodystrophy
arylsulfatase A deficiency cerebroside sulfate accumulates

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