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2015

GENETICS OF
DEVELOPMENT
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Development represents:
The biochemical, morphological, physiological
changes during all the life (from birth up to
death),
which are under genetic control and realize in
specific individual environment condition
(maternal factors, personal internal factors,
external factors).

The main steps of

ontogenesis

fertilization
prenatal development
postnatal development
ageing, death

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Errors during fertilization

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Control of development
Genetic program of zygote
Maternal factors
Environmental factors

The sexual process is required

for normal development
There is a differentiated contribution of
genetic material inherited from mother and
father genetic dosage;
The presence of both genomes is required
for normal development (genomic
imprinting, uniparental disomy)

The chances of zygote to survive - 1:80.

50% of zygotes die before implantation.
50-60% of embryos carry a chromosomal
mutation and are eliminated.
0,5-0,7% of new-borns are carriers of a
chromosomal aberration.

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Maternal effect
Cytoplasmic inheritance mitochondrial
DNA;
mRNA synthesized during oogenesis;
Asymmetric distribution of molecules in
cytoplasm of egg cell - cytoplasmic
determinism;
Metabolic substances that pass trough
placenta.
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Environment effect
Teratogen factors:
physical (irradiations)
chemical (drugs, alcohol ...)
biological (viruses, toxins ...)

May induce abnormalities:

Congenital abnormalities;
Phenocopies.
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The effect of
thalydomyde on
development

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The mechanisms of
congenital abnormalities

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Normal genetic factors + favourable

environmental conditions normal
development.
Normal genetic factors + unfavourable
environmental conditions abnormal
development.

Abnormal genetic factors (mutations) +/unfavourable environmental conditions

abnormal development.
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Types of congenital
anomalies

Malformations
Deformations
Disruptions
Abnormal histogenesis (displasia)

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Malformations
Morphologic defect of an organ as result
of internal effect abnormal primordium
embryo abnormality
Examples:
agenesis (kidney agenesis);
Partial development (cleft leap;
syndactily); excessive development
(polydactily).
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Deformation
Deformation abnormal shape of a part of body
determined by pressure or other mechanical
forces. Its derived from normal primordium.

Ex: clubfoot deformity.

Factors:
Small uterus;
Olygohydroamnios;
Abnormalities of CNS
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Disruption a morphological defect of a part

of organism determined by breaks.
Abnormalities fetal abnormalities.
Determined by teratogen factors.
Ex: amniotic bridges may cause amputations or
other abnormalities

Dysplasia abnormal tissue development =

dyshistogenesis.
Ex: abnormal cartilages.
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Causes of congenital
abnormalities

Idiopathic (unknown factors) 60%

Multifactorial 20%
Monogenic 7,5%
Chromosomal 6%
Maternal factors 3%
Congenital infections 2%
Drugs, alcohol, radiations 1,5%
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Cell events during

development

Cell proliferation
Cell differentiation
Cell-cell interactions
Cell migration
Apoptosis

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Cell differentiation

Differential gene expression

Cell specialization
Irreversible

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Cell-cell interactions
Interactions between equivalent cells;
Interactions between non-equivalent
adjacent cells;
Interactions between non-equivalent
non-adjacent cells, through hormones,
growth
factors
and
respective
receptors.

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Apoptosis
Assures the shape, volume and proportions
of organs;
Selection of mutant cells;
Regression of provisory organs;
Elimination of old cells;
Elimination of tumoral cells.

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Genetic control of
development

Segmentation genes
Homeotic genes
Hox proteins
Transcription factors
Growth factors
Lethal mutations

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Homeotic genes

Control formation of an organ or a region

of body
Contain a highly conserved sequence of
DNA Homeo-box (180 bp) which
correspond to homeodomens in proteins
In humans there are 4 gene families
HoxA, HoxB, HoxC, HoxD 38 genes

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Genetic mechanisms in
human development

Genomic imprinting
Uniparental disomy
Cell mosaics
Cell selection during embriogenesis
X chromosome inactivation
Telomarase activity

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Genomic imprinting
Genomic imprinting control of genetic
dosage through selective inactivation of
genes inherited from mother or father :
DNA methilation
DNA heterochromatinisation
Effect of position.

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Uniparental disomy
Zygote contains two cromosomes inherited
from the same parent:
Disomy in a gamete followed by removing
of an additional chromosome;
Robertsonian translocation.
Ex:
7, 14 and 15 from mother,
11, 14 and 15 from father
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Aneuploidy resque
Correction of abnormal number of
chromosomes, through elimination of
supernumerary chromosomes (trisomy) or
achieving of absent chromosome (monosomy).

Non-disjunction
Anaphase lag
Endoreplication
Transverse cleavage

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Mosaics
In all tissues
In some embryonic tissues
In placenta

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The consequences of
mosaics
Abnormal embryonic development;
Developmental retardations, miscarriages;
Perinatal death.

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