Developmental Genetics

Question 1

errors occurring in the initial formation of structures like cleft lip or polydactyly

Answer 1

malformation

Question 2

disturbances after an organ has been formed due to external forces and not genetics like shortened arms or legs due to vascular problem

Answer 2

disruptions

Question 3

mechanical distortions like club foot due to lack of amniotic fluid

Answer 3

deformation

Question 4

abnormalities in tissue organization like thanatophoric dysplasia

Answer 4

dysplasia

Question 5

cascades of effects

Answer 5

sequences

Question 6

groups of anomalies that consistently occur together due to a single underlying cause

Answer 6

syndromes

Question 7

traits coincide more often than expected with chance

Answer 7

association

Question 8

induces cell proliferation and involved in tissue patterning

Answer 8

sonic hedgehog genes

Question 9

type of patterning in sonic hedgehog genes

Answer 9

dorsal ventral patterning

Question 10

sonic hedgehog derived from

Answer 10

neural ectoderm such as notochord and ventral floor plate of neural tube

Question 11

zone of polarizing activity for sonic hedgehog genes

Answer 11

limb patterning

Question 12

sonic hedgehog involved in the development of what

Answer 12

hair follicles, tooth, lung, pancreas

Question 13

what role does sonic hedgehog play in the patched gli pathway

Answer 13

it binds to the PTCH and relieves the inhibition of SMO therefore activating downstream signaling

Question 14

what inhibits SMO in the patched gli pathway

Answer 14

PTCH

Question 15

how is sonic hedgehog prepared or modified before it binds to the PTCH

Answer 15

it is cleaved to an active N terminal form then cholesterol is added to it

Question 16

what happens when the Gli protein and CREBBP interact in the PTCH gli pathway

Answer 16

they activate gene expression by binding to the regulatory sequence on DNA

Question 17

where is SHH located on humans

Answer 17

distal long arm of chromosome 7

Question 18

heterozygous mutation of SHH results in what?

Answer 18

autosomal dominant holoprosencephaly

Question 19

clinical variability in people that present with holoprosencephaly

Answer 19

facial abnormalities (cyclopia, premaxillary agenesis, mild hypotelorism, or a single central maxillary incisor) to mild microcephaly alone.

Question 20

increased SHH in the frontal nasal prominence that promotes mediolateral expansion of the face and ventral forebrain

Answer 20

hypertelorism

Question 21

what does HOX gene pattern

Answer 21

anterior-posterior of the vertebrate embryo and limb bud

Question 22

what activated HOX gene expression

Answer 22

gradient of SHH which is created by ZPA (zone polarizing activity)

Question 23

what leads to polydactyly

Answer 23

overexpression of SHH in the limb bud and mutation in the Gli3

Question 24

holoprosencephaly is caused by a mutation where

Answer 24

in the SHH or Six3 gene

Question 25

mild effects such as single incisor, moderate effects such as cleft lip and palate, to severe effects such as cyclopia are all what?

Answer 25

variability in SHH mutation (SN: there is no correlation between specific mutation in SHH and phenotype)

Question 26

mutation in 7 dehydrocholesterol reductase

Answer 26

Smith Lemi Optiz Syndrome (SLOS)

Question 27

SLOS phenotype

Answer 27

microcephaly, mental retardation, malformation of mesodermal origin, syndactly, and polydactyly

Question 28

mutation in patched (ptc)

Answer 28

gorlin syndrome (nevoid basal cell carcinoma)

Question 29

rare mutation in gli gene

Answer 29

pallister hall syndrome (brain tumors and polydactyly)

Question 30

mutation in CREBBP gene

Answer 30

Rubinstein-Taybi Syndrome

Question 31

broad thumbs and toes, mental disability, short stature, small head, facial features

Answer 31

mutation in CREBBP gene

Question 32

patterning of anterior posterior body axis is done by

Answer 32

overlapping HOX gene expression

Question 33

what happens if there is a mutation in the hox genes in fruit fly

Answer 33

unusual transformation of body segment identity

Question 34

why doesn't a mutation in mammalian hox genes show dramatic changes

Answer 34

because we have other hox genes/clusters that will come in and take the place of a mutated one

Question 35

in humans what happens if there is a single loss of a hox gene

Answer 35

it increases childhood susceptibility to leukemia

Question 36

what must be done to see a dramatic change in mammalians

Answer 36

must completely knock out all the hox genes in that area

Question 37

children with extra cervical rib have a higher frequency for cancer than general population so what does that mean

Answer 37

low reproductive fitness

Question 38

polydactyly is a result of what

Answer 38

disruption in hoxd13 gene

Question 39

achondroplasia is a result of mutation where

Answer 39

FGFR3 (fibroblast growth factor receptor 3) with a G-C transversion at nucleotide 1138 ath the transmembrane domain

Question 40

80% of achondroplasia is due to what?

Answer 40

80% - spontaneous mutation during spermatogenesis 20% - inherited from one parent

Question 41

how do chondrocytes develop

Answer 41

sequentially through reserve (R), proliferating (P), prehypertropic (PH), and hypertropic stages

Question 42

function of FGFR3

Answer 42

inhibit chondrocyte growth and differentiation in the growth plate of developing long bones

Question 43

in achondroplasia, there is a substitution of what and where

Answer 43

arginine replaced with glycine at position 360 on the FGFR3 protein

Question 44

less severe to most severe mutation of FGFR3 mutation

Answer 44

hypochondroplasia, achondroplasia, SAADAN dyplasia, thanatophoric dysplasia

Question 45

hypochondroplasia is mutation where

Answer 45

proximal (more common) and distal tyrosine kinase domain

Question 46

thanatophoric dysplasia is mutation where

Answer 46

extracellular domain and distal tyrosine kinase domain (lethal)

Question 47

what is deleted in infertile male

Answer 47

Regions AZFa, b, c (azoospermia factor)

Question 48

what happens in presence and absence of Y chromosome

Answer 48

presence - testes develop | absence - ovaries develop

Question 49

gonadal differentiation is determined by

Answer 49

presence or absence of SRY gene located on Y chromosome that produces testis determining factor (TDF)

Question 50

what does testis produce

Answer 50

anti mullerian duct hormone that destroys mullerian duct and testosterone

Question 51

46 XX Male sydrome (de la Chapelle syndrome) is caused by what

Answer 51

translocation of the SRY gene on the Y chromosome due to unequal crossing over during meiosis (Y translocated onto X)

Question 52

characteristics of de la chapelle syndrome

Answer 52

10% hypospadias, mullerian tissue absent, short, infertile

Question 53

46 XY female Swyer syndrome (pure gonadal dysgenesis) is caused by

Answer 53

loss of function mutation of SRY gene

Question 54

characteristics of Swyer syndrome

Answer 54

normal femae genitalia, mullerian ducts present, LH increased so clitoromegaly, bilateral streak gonads instead of ovaries or testes, delayed puberty

Question 55

treatment of swyer syndrome

Answer 55

estrogen and progesterone, streak gonads removed

Question 56

polymorphic markers on Y chromosome has been used to trace whom

Answer 56

human from their migration from Africa