Genetics of Development

Question 1

Regulative Phase

Answer 1

• -first phase of development
• -loss of a cell will not hurt the embryo (neighboring cells will compensate)
• -cells are functionally equivalent
• -

Question 2

Embryonal Period

Answer 2

–week 1-8

Question 3

Implantation occurs at?

Answer 3

–day 7-12 after fertilization

Question 4

Mosaic Phase

Answer 4

• -loss of a cell cannont be compensated for
• -leads to loss of part of tissue for whatever that cell was going to contribute to
• defects in mosaic phase can lead to birth defects

Question 5

Phases of Development

Answer 5

• -regulative
• -mosaic
• -axis formation

Question 6

3 Axes that need to be defined

Answer 6

• -head to toe (cranial-caudal)
• -dorsal-ventral
• -left-right

Question 7

First Visible Structure in embryo

Answer 7

• -anterior/posterior axis

- -defined by primitive streak

Question 8

Primitive Streak/Anterior-Posterior development

Answer 8

• -marks the groove at which ectodermal cells invade into the space between epiblast and hypoblast to form separate germ layer
• -gene called nodal is required for formation of primitive streak
• -anterior end of streak is the node

Question 9

Dorsal Ventral Development

Answer 9

• -induced by gene products of noggin and chordin genes

- -concentration dependent manner (gradient)

Question 10

Left-Right Asymmetry

Answer 10

• -causes by asymmetric expression of Shh gene from notochord
• -sinus inversus (organs on opposite side of body they should be)
• -Shh also used in concentration dependent manner

Question 11

Patterning

Answer 11

• -occurs after axes have been established
• -Hox genes encode DNA homeobox binding transcription factors
• -each tissue expresses different combo of hox genes depending on location of that specific tissue

Question 12

Hox genes

Answer 12

• -used in patterning development
• -transcription factors
• -expressed in response to morphagens (nodol, noggin, Shh, chordin)
• -4 Classes HoxA-D
• -13 members of each class
• -larger numbers deal with cells/tissues more distal (think pinky finger would be like HoxD-13)

Question 13

5 Mechanisms operating at cellular level during development

Answer 13

• -gene regulation by transcription factors
• -cell-cell signaling (by direct contact or secretion of morphogens)
• -development of specific cell shape and polarity
• -movement and migration of cells
• -programmed cell death or apoptosis

Question 14

Cause of Defect described by what terms?

Answer 14

• -malformation
• -deformation
• -disruption

Question 15

mechanism by which one defect causes multiple abnormalities is described by?

Answer 15

–sequence and syndrome

Question 16

Malformation

Answer 16

• -result from an intrinsic abnormality in the developmental process
• -ex. polydactyly
• -originate from defect within affected organ

Question 17

Deformations

Answer 17

• -results from extrinsic influence on development of affected tissue
• -ex. oligohydraminos (lack of amniotic fluid–causes constraint on development fetus–no room to expand)

Question 18

Disruptions

Answer 18

• -result from destruction of developing tissue

- -ex. amniotic bands–wrap around developing tissue, cut off blood supply, killing tissue

Question 19

Isolated Anomalies

Answer 19

• -ex. cleft palate
• -affect single body region
• -sporadic or multifactorial
• -60% of major birth defects are

Question 20

Sequence

Answer 20

• -cascade of events starting from a single isolated anomaly and leading to multiple malformations
• -sequences are usually sporadic or multifactorial
• -disease phenotypes are present sequentially

Question 21

Syndrome

Answer 21

• -when all disease phenotypes are caused by a single defect

- -affects several body regions and most often display chromosomal or mendelian inheritance

Question 22

Robin Sequence

Answer 22

• -series of events that starts w/ retardation of mandibular growth (due to variety of different possible defects; see slide)
• -displaces tongue posteriorly and prevents closing of palatal shelves

Question 23

Damage of Embryo Weeks 1-4

Answer 23

• -blastogenesis
• -multiple major abnormalities in entire embryonic regions
• -ex. VACTRL

Question 24

Damage of Embryo Weeks 5-8

Answer 24

• -organogenesis
• -abnormalities in specific organs, single major anomalies
• -ex. congenital heart defects

Question 25

Damage after week 9

Answer 25

• -after organ formation
• -mild effects
• -ex. presence of single palmar crease

Question 26

VACTERL

Answer 26

• -vertebral, anal atresia, cardiac, tracheo-esophagal fistula, renal and radial limb defects
• -weeks 1-4
• -maternal diabetes is risk factor

Question 27

Rate of Children Born w/ birth defect

Answer 27

–2-3%

Question 28

Most Common Birth Defects and their prevalences

Answer 28

• -heart defects: 1/100-200 live births
• -pyloric stenosis: 1/300
• -neural tube defects: 1/1,000
• -orofacial clefts: 1/700-1,000
• -clubfoot: 1/1,000

Question 29

Birth defects account for % of infant mortality (% if premature births included)

Answer 29

• -20% infant mortality

- -40% w/ premature births

Question 30

Inheritance of genetic defects that cause birth defects

Answer 30

• -50% have complex inheritance
• -25% are caused by chromosomal defects
• -25% are caused by single gene mutations
• -in only about 5% of cases, the malformation can be traced to non-genetic factors (smoking, drinking, drugs, maternal meds and infections)

Question 31

Development is…? (2 general characteristics)

Answer 31

• -tightly regulated: even one additional cell division during early development is likely fatal; extra division in late development may give segmental growth
• -Extremely robust: disturbances to normal developmental process occur regularly; these are countered by regulatory mechanisms

Question 32

Genetically similar mice in same environment have mutation of foramin

Answer 32

• -only 20% have renal defects

- -shows that lots of development is left up to chance