Developmental Genetics-Lecture18

Question 1

define: malformations

Answer 1

Due to errors occurring in the initial formation of structures, a primary structural defect

Question 2

define: disruptions

Answer 2

Disturbances after an organ has been formed (external forces, not genetics).
eg: phocomelia

Question 3

define: deformations

Answer 3

mechanical distortions; eg: club foot; normal corrects after birth

Question 4

define dysplasias

Answer 4

abnormalities in tissue organization; most are monogenic

eg: thanatophoric dysplasia due to FGF3R mutation

Question 5

Name 4 types of single abnormalities

Answer 5

1) Malformation
2) Deformation
3) Disruption
4) Dysplasia

Question 6

Name 3 types of multiple abnormalities

Answer 6

1) sequences
2) syndromes
3) associations

Question 7

define: sequences

Answer 7

cascades of effects

eg: Potter sequence due to decreased amniotic fluid

Question 8

define: syndromes

Answer 8

Groups of abnormalities that consistently occur together due to a singled underlying cause.
eg- Down Syndrome d/t trisomy 21

Question 9

define: associations

Answer 9

Occurs when traits coincide more often than expected by chance

Question 10

Sonic Hedgehog Genes

Answer 10

Induce cell proliferation and involving in tissue patterning (spacial and temporal components)
eg: notochord sends signals to overlying neuroectoderm to form neural tube (Dorsal/ventral patterning)
eg: zone of polarizing activity (ZPA)-limb patterning
Hair, tooth, lung, pancreas

Question 11

Outline the Sonic Hedge Hog pathway

Answer 11

modified Shh binds Ptch, which removes Ptch’s inhibition on SMO –>Gil and CREBBP interact and active gene expression

Question 12

hypertelorism

Answer 12

A condition involving mediolateral expansion of the face and ventral forebrain. Due to increased SHH in frontal nasal prominence

Question 13

Relate Hox gene to SHH and ZPA

Answer 13

Limb bud: gradient of SHH protein, produced by ZPA, establishes Hox gene expression

Question 14

Hox genes

Answer 14

Pattern anterior-posterior axis of vertebrate embryo and axis of vertebrate limb bud

Question 15

Name some diseases associated with the SHH signal pathway

Answer 15

Holoprosencephaly
Smith-Lemi-Opitz Syndrome
Gorlin Syndrome
Pallister-Hall Syndrome
Rubinstein-Taybi Syndrome

Question 16

Holoprosencephaly

Answer 16

mutation in SHH or Six3 gene (regulator)

spectrum of defects including: cleft lip/ palate, single incisor, cyclopia

Question 17

Smith-Lemi-Opitz Syndrome

Answer 17

mutation in 7-dehydrocholestrol reductase (important for cholesterol modification of SHH)
microencephaly, MR, mesodermal malformations, syndactly, polydactyly

Question 18

Gorlin Syndrome

Answer 18

mutation in PTCH

Early age basal cell carcinoma

Question 19

Pallister-Hall Syndrome

Answer 19

mutation in Gli genes
-brain tumors, polydactyl
very rare

Question 20

Rubinstein-Taybi Syndrome

Answer 20

mutation in CREBBP gene

-broad thumb and toes, mental disability, short stature, small head

Question 21

Disruption of Hoxd13 gene

Answer 21

leads to polydactyly

Question 22

Achondroplasia

Answer 22

Full penetrance, autosomal dominant