19 Developmental Genetics

Question 1

What is needed for an organism to grow form a single cell?

Answer 1

Differential gene expression

Question 2

What are the 4 developmental patterns that can be gained from animal models?

Answer 2

Axis specification. Pattern formation. Organogenesis. Induction/polarity

Question 3

What are the six animal models mentioned and their scientific names?

Answer 3

C.elegans(nematode) D.melanogaster(fruit fly) D.rerio(zebrafish) X.laevis(clawed frog) G.gallus(chicken) M.musculus(mouse)

Question 4

Pro/con of C.elegans model

Answer 4

Short generation, know cell fate/invertebrate

Question 5

Pro/con of D.melanogaster model

Answer 5

Short gen, easy breeding, high mutation/maintenance

Question 6

Pro/con of D.rerio model

Answer 6

Transparent embryo, easy breeding/small embryo

Question 7

Pro/con of X.laevis model

Answer 7

Large embryo/tetraploid

Question 8

Pro/con of G.gallus model

Answer 8

Large embryo/genetics difficult (genome is mapped now however)

Question 9

Pro/con of M.musculus model

Answer 9

Easy breeding, mammal/embryo small

Question 10

Which genetic mediators interact between nearby cells?

Answer 10

Paracrine signaling molecules

Question 11

Which genetic mediators control gene expression and respond to external stimuli?

Answer 11

DNA transcription factors

Question 12

Which genetic mediators facilitate migration and is scaffolding?

Answer 12

Extracellular Matrix proteins

Question 13

What are the four mentioned paracrine signaling molecules?

Answer 13

Fibroblast Growth factor(FGF), Hedgehog proteins, Wingless family(Wt), Transforming growth factor beta(TGF-beta)

Question 14

What can be affected in paracrine signaling mutations?

Answer 14

Receptor or molecule

Question 15

What expresses FGFR3?

Answer 15

Growing bones

Question 16

What results from FGFR mutations?

Answer 16

Autosomal dominant, skeletal dysplasias depending on how severe

Question 17

What are the three forms of FGFR3 mutation phenotypes?

Answer 17

Achondroplasia - most common, short limbs, microcephaly // hypochondroplasia - milder form // thanatophoric dysplasia - lethal, very short limbs, receptor highly activated

Question 18

What are the three mentioned transcription factors mentioned?

Answer 18

Homeobox - HOX //High mobility group - SOX // T-box - TBX

Question 19

What is the archetype of the SOX family

Answer 19

SRY gene of Y -> regulates SOX9, high in males, low in females, mammalian testis determining factor

Question 20

What does SOX9 regulate? What will mutation do?

Answer 20

Chondrogenesis and Col2A1. Mutation = camptomelic dysplasia = short limbs, female XY

Question 21

What is Hirschsprung diseases and what gene of the SOX family can cause it?

Answer 21

Neural crest defect causing colon hypomobility, males 4x risk, SOX10 mutation

Question 22

What are the four main ECM proteins mentioned?

Answer 22

Collagens, fibrilins, elastin and laminin

Question 23

What disease results from Type I collagen gene mutation?

Answer 23

Osteogenesis imperfecta due to mutation in glycine within fibrils = bone disruptions mild to lethal

Question 24

What can a mutation of Fibrillin 1 and elastin cause?

Answer 24

Marfan’s syndrome leading to heart and large blood vessel problems along

Question 25

What are the phenotypic results of marfans?

Answer 25

Tall/lanky, arachnodactyly, lens displacement

Question 26

What can a mutation of laminin gene LAMC2 cause?

Answer 26

Junctional epidemoylysis bullosa leading to large blisters on the skin

Question 27

What is the function of laminin?

Answer 27

Anchors cells to ECM

Question 28

What is pattern formation?

Answer 28

How tissues and organs are established thus position and cell differentiation

Question 29

What processes is Sonic Hedgehog SHH gene involved in?

Answer 29

Neural tube/somite/limbs and the left-right axis

Question 30

What is cell fate?

Answer 30

Type, fxn and longevity

Question 31

What results form a severe defect in SHH gene cause?

Answer 31

Midline brain development leading to holoprosencephaly

Question 32

What does the SHH bind to?

Answer 32

Membrane Cholesterol

Question 33

Which genes are the axes of the body determined by?

Answer 33

4 clusters of put to 13 genes = 39 total HOX genes

Question 34

genes in the same relative position (ie. HOX) are called?

Answer 34

Paralogs

Question 35

Define temporal colinearity and spatial colinearity

Answer 35

Temporal - genes on the 3’ end will be expressed sooner//Spatial - genes on the 3' will be expressed more at the “front”(anterior) of the protein sequence

Question 36

Define Homeotic transformation

Answer 36

When HOX genes are not in correct sequence/combination -> affected area transforms to another part

Question 37

What signals define the Ventral axis? Dorsal? Lateral?

Answer 37

Ventral - Bmp4 // Dorsal - Noggin, Chordin binds off Bmp4 // Lateral - equal amounts of SHH

Question 38

Laterality defects can cause what two anomalies?

Answer 38

Situs ambiguus or situs inversus

Question 39

With a ZIC3 protein what may occur in males and females?

Answer 39

Males - situs ambiguus // females - situs inversus

Question 40

Which is a candidate gene for limb induction and what maintains its expression?

Answer 40

FGF8 of the mesoderm induces, WNT2b/8c maintains its expression

Question 41

Growth of the limb bud is stimulated by which three signals?

Answer 41

FGF2/4/8

Question 42

The zone of polarizing activity(ZPA) uses what to maintain the apical ectodermal ridge?

Answer 42

SHH

Question 43

What is a typical anterior axis defect, signs and gene affected?

Answer 43

Holt-Oram syndrome leading to shortened or missing radius and thumbs. T-box gene TBX5 is mutated

Question 44

What is a typical posterior axis defect, signs and gene affected?

Answer 44

Ulnar mammary leading to deformed upper limbs and chest on the ulnar side. TBX3 gene (related to TBX5) is responsible

Question 45

What gene drives pancreatic development, maturation, differentiation as well as insulin release?

Answer 45

IPF1

Question 46

What are two animal models used commonly to test specific genes as well as its effect upon deletion?

Answer 46

Transgenic and knockout mice