Exam #5: Genetics of Development

Question 1

Regulative Development

Answer 1

Cells are functionally equivalent & loss of a cell can be compensated for resulting in normal development

Question 2

Mosaic Development

Answer 2

• Occurs after the regulative phase

- A loss of cells cannot be compensated for and will result in abnormal development

Question 3

Pre-implantation Diagnosis

Answer 3

• Removing a cell in the morula phase i.e prior to implantation, to test for chromosomal aberrations
• Will NOT have a detrimental impact on development
• Regulative phase

Question 4

What is the first visible axis in the developing embryo?

Answer 4

• Primitive Streak, the groove at which invasion occurs in gastrulation
• Anterior/posterior axis
• Induced by Nodal

Question 5

Function of the Node

Answer 5

Secrete noggin & chordin to define the dorsal/ ventral axis

Question 6

Endoderm

Answer 6

• Cells of the gut

- Lung eipthelium

Question 7

Mesoderm

Answer 7

• Bone
• Muscle
• Internal organs

Question 8

Ectoderm

Answer 8

• Skin

- Nervous System

Question 9

What are the three axes in the embryo? What factors regulate their development?

Answer 9

1) Anterior-Posterior (Cranial- Caudal)= Nodal
2) Dorsal-Ventral= Noggin & Chordin
3) Left-Right= Shh
* All are secreted proteins*

Question 10

Patterning

Answer 10

Division of the embryo into segments to define where the parts will go

Question 11

HOX

Answer 11

• Transcription Factor with a special DNA binding domain

- Determines patterning along the anterior/posterior axis

Question 12

What are the five processes by which cells participate in development?

Answer 12

1) Gene regulation by transcription factors & chromatin modification
2) Cell-cell signaling
3) Development of a specific cell shape and polarity
4) Movement & migration of cells
5) Programmed cell death

Question 13

Malformation

Answer 13

• Result from an intrinsic abnormality in the developmental process
• E.g. polydactyly

Question 14

Deformation

Answer 14

• Result from an extrinsic influence on the development of an affected tissue
• E.g. Oligohydraminois, or a lack of amniotic fluid that puts constraint on the developing fetus

Question 15

Disruption

Answer 15

• Destruction of what was an otherwise normal tissue

- E.g. amniotic bands wrapping around fetal limbs & choking off the blood supply (causes amputation)

Question 16

Sequence

Answer 16

• A cascade of events from an isolated anomaly & leading to multiple malformations
• Phenotypes are caused sequentially by a single defect
• E.g. the Robin Sequence

Question 17

Syndrome

Answer 17

All of the disease phenotypes are caused by a single defect simultaneously

Question 18

What is the impact of problems that arise in the first four weeks of development?

Answer 18

• “Blastogenesis”
• Produce major abnormalities that affect entire embryonic regions
• E.g. VACTERL

Question 19

What is the impact of problems that arise between weeks 5 & 8?

Answer 19

• “Organogenesis”

- Affect single organs and produce single major anomalies

Question 20

What is the impact of problems that arise after week 8?

Answer 20

• Minor affect on the individual

Question 21

What are the five most frequent birth defects?

Answer 21

• Heart Defects (1/100-1/200)
• Pyloric Stenosis (1/300)
• Neural Tube Defects (1/1,000)
• Orofacial Clefts (1/700-1/1,000)
• Clubfoot (1,1000)

Question 22

Situs Inversus

Answer 22

• Developmental defect of the left/right axis
• Internal organs are reversed or mirrored from their normal positions
• Caused by a Shh problem

Question 23

Situs Ambiguious

Answer 23

• Severe developmental defect of the left/right axis

- Orientation of the internal organs is random

Question 24

Isolated Anomaly

Answer 24

• Effects a single body region only

- E.g. cleft palate

Question 25

VACTERL

Answer 25

• Vertebral
• Anal Atresia
• Cardiac
• Tracheo-Esophageal Fistula
• Renal
• Radial Limb Defects

Maternal diabetes is a major risk factors, and the disease is caused by damage to the mesoderm ~20-25 days

Question 26

What are the most frequent causes of birth defects?

Answer 26

• 50% are multifactorial
• 25% are chromosomal defects
• 20% are single-gene mutations
• 5% are teratogenic

Question 27

What structure expresses Shh?

Answer 27

Notochord

Question 28

What initiates left-looping of the heart tube?

Answer 28

Asymmetric expression of Shh, and subsequent left-sided expression of Nodal

Question 29

Describe the three axes of the developing limb.

Answer 29

1) Shoulder-to-fingertip= proximal-distal
2) Thumb-to-fifth finger= anterior-posterior
3) Dorsum-to-palm= dorsal-ventral

Question 30

How does the expression of HOX correlate with the structure of the developing embryo?

Answer 30

• Expression correlates with position

- Lower # HOX genes specify structures that are more anterior

Question 31

Describe the Robin sequence.

Answer 31

• Sequence of events that starts with an isolated anomaly, retardation of mandibular growth
• Displaces the tongue posteriorly
• Prevents closing of the palatal shelves
• Causes a cleft palate

Question 32

List the five most frequently observed birth defects.

Answer 32

1) Heart Defect
2) Pyloric stenosis
3) Neural tube defects
4) Orofacial clefts
5) Clubfoot