Exam 5: Genetics of Development - Principles

Question 1

anterior/posterior axis

Answer 1

first visible structure in embryo

defined by primitive streak, marks groove at which ectodermal cells form 3 germ layers

Question 2

axes in the developing limb

Answer 2

shoulder-to-fingertip is proximal-distal
thumb-to-fifth-finger is anterior-posterior
dorsum-to-palm is dorsal-ventral

Question 3

blastocyst

Answer 3

hollow sphere containing group of cells called inner cell mass
16 cell embryo (morula) transforms into blastocyst

Question 4

chordin

Answer 4

secreted from cells in node and induce dorsal development in concentration-dependent manner

Question 5

clinical dysmorphology

Answer 5

describes etiology of birth defects and gives valuable clues about underlying abnormality in development process

Question 6

deformations

Answer 6

result from extrinsic influence on development of affected tissue
defect from outside
lack of amniotic fluid constrains fetus because not enough room to expand - can lead to contractures of limbs

Question 7

disruptions

Answer 7

destruction of developing tissue

amniotic bands sometimes wrap around developing fetal limbs, choke off their blood supply & tissue is destroyed

Question 8

ectoderm

Answer 8

develops from epiblast

forms skin and nervous system

Question 9

embryonal period of development

Answer 9

after fertilization of an egg, begins with 4 cell divisions without cell growth
lasts from week 1 to week 8

Question 10

endoderm

Answer 10

forms gut and lung epithelium

Question 11

epiblast

Answer 11

formed from inner cell mass

goes on to form the embryo - upper cell layer

Question 12

formin and renal aplasia

Answer 12

mutation in formin gene in mice causes renal aplasia in about 20% of mice
All mice were genetically and environmentally identical - means another cause of reduced penetrance
formin mutation can be tolerated - formin mutation does not cause, but rather increases probability for developing renal aplasia

Question 13

gastrulation

Answer 13

produces primitive streak - first axis of embryo

creates three germ layers - endoderm, mesoderm, and ectoderm

Question 14

homeobox genes (HOX)

Answer 14

determines patterning (division into segments to define part development) along anterior/posterior axis
family of transcription factors - contain homeodomain, a DNA binding domain
4 HOX clusters on 4 chromosomes
expression of each of genes in cluster correlates with position of cell and timing of expression
Each cell along axis experiences different ration of expression of different HOX genes - code for fate of cell

Question 15

homeodomain

Answer 15

DNA binding domain contained in homeobox (HOX) genes

Question 16

inner cell mass

Answer 16

in blastocyst - forms epiblast

Question 17

isolated anomalies

Answer 17

affect a single body region
usually either sporadic or multifactorial
about 60% of major birth defects
i.e. cleft palate

Question 18

major anomalies

Answer 18

anomalies with surgical or cosmetic consequences, like cleft lip or amputated limb

Question 19

minor anomalies

Answer 19

have little impact on well being of patient

give important diagnostic clues about presence of a syndrome

Question 20

malformations

Answer 20

result from intrinsic abnormality in developmental process

defect comes from within

Question 21

mesoderm

Answer 21

form bone, muscles, and most internal organs

Question 22

morula

Answer 22

16 cell embryo

transforms into blastocyst

Question 23

mosaic phase

Answer 23

begins after gastrulation
loss of a cell in this phase cannot be compensated - will lead to loss of tissue
affects baby - removal of cells for screening needs to be done before this phase

Question 24

regulative phase

Answer 24

cells functionally equivalent - loss of a part of embryo can be compensated for by neighboring cell
ends with gastrulation

Question 25

nodal

Answer 25

gene required for formation of primitive streak & later for formation of left/right axis soluble protein secreted into extracellular space - diffuses through tissue and establishes gradient - NOT a transcription factor (because it can leave the cell)

Question 26

noggin

Answer 26

protein secreted from cells in the node | induce dorsal development in concentration-dependent manner

Question 27

polydactyly

Answer 27

``` extra digits (in hands/feet) mutations interfere with developmental process of limbs originate from defect within affected organ - malformation ```

Question 28

primitive streak

Answer 28

defines first axis of embryo, produced by gastrulation | marks groove at which ectodermal cells invade space between epiblast and hypoblast to form 3 germ layer

Question 29

Robin sequence

Answer 29

causes cleft palate extrinsic constraint on fetus (from low amount of amniotic fluid) interferes with growth of jaw - small chin tongue pushes into forming hard palate & blocks formation - forms u-shaped cleft palate

Question 30

segmental overgrowth

Answer 30

consequence of dysregulation during development - can occur from just one additional cell division per affected cell - loss of control over cell division

Question 31

sequence

Answer 31

cascade of events starts from isolated anomaly and leads to multiple malformations - usually sporadic or multifactorial phenotypes caused sequentially by singe defect

Question 32

syndrome

Answer 32

affect several body regions and most often display chromosomal or Mendelian inheritance present when disease phenotypes are caused by single defect simultaneously

Question 33

situs ambiguus

Answer 33

caused by defects in left/right axis formation serious condition in which orientation of organs is randomized usually accompanied by heart defects

Question 34

situs inversus

Answer 34

caused by defects in left/right axis formation all of organs are in complete mirror image of where normally found usually asymptomatic

Question 35

Sonic hedgehog (Shh)

Answer 35

signaling protein from notochord (precursor of spine) left/right asymmetry caused by asymmetric expressions of this gene - leads to left side expression of nodal, which initiates left-looping of heart tube

Question 36

Dorsal/ventral axis

Answer 36

specified by noggin and chordin in concentration dependent manner

Question 37

time of implantation

Answer 37

day 7 to 12

Question 38

Treacher-Collins Syndrome

Answer 38

autosomal dominant small jaw, down slanting palpebral fissuers, malar hypoplasia, cleft palate risk for complications is high and surgery risky

Question 39

VACTERL association

Answer 39

Vertebral, Anal atresia, Cardiac, Tracheo=Esophagal fistula, Renal and Radial Limb defects) abnormality that occurs during first 1-4 weeks of development causes multiple major abnormalities in entire embryonic regions originates from damage to developing mesoderm at 20-25 days after conception maternal diabetes is a major risk factor

Question 40

Abnormalities occurring from week 5 to 8

Answer 40

affect specific organs & produce single major anomalies - congenital heart defects

Question 41

Abnormalities occurring after week 9

Answer 41

have mild effect on individual

Question 42

What percentage of children are born with a birth defect?

Answer 42

2-3%

Question 43

What is the percentage of mortality of children with birth defects?

Answer 43

20%, most common cause of infant death in US

Question 44

What are the most common birth defects

Answer 44

Heart defects, pyloric stenosis, neural tube defects, orofacial clefts, clubfoot

Question 45

What is the prevalence of heart defects?

Answer 45

1/100 - 1/200 live births

Question 46

What is the prevalence of pyloric stenosis?

Answer 46

1/300

Question 47

What is the prevalence of neural tube defects?

Answer 47

1/1,000

Question 48

What is the prevalence of orofacial clefts?

Answer 48

1/700 - 1/1,000

Question 49

What is the prevalence of club foot?

Answer 49

1/1,000

Question 50

Percentage of birth defects with complex/ multifactorial inheritance

Answer 50

50%, no identifiable cause

Question 51

Percentage of birth defects caused by chromosomal defects

Answer 51

25%

Question 52

Percentage of birth defects caused by single-gene mutations

Answer 52

20%

Question 53

Percentage of birth defects caused by non-genetic factors (maternal medication and infections

Answer 53

5%

Question 54

pre-implantation diagnosis

Answer 54

in morula phase (before mosaic phase) a cell can be removed from embryo and examined for chromosomal aberrations without harming embryo 15 remaining cells develop into normal embryo

Question 55

5 processes by which cells participate in development

Answer 55

Gene regulation by transcription factors and chromatin modification Cell-cell signaling, either by direct contact or by secretion of morphogens Development of specific cell shape and polarity Movement and migration of cells Programmed cell death

Question 56

robustness

Answer 56

countering of factors capable to disturb orderly development | recognized by cell and regulatory mechanisms used