Presentation

on genetics
and teratology

SUBMITTED TO: MRS R. SUBMITTED BY :P.

ANITHA MADAM SONIYA
LECTURER MSC NURSING 1ST YEAR
GOVT COLLEGE OF GOVT COLLEGE OF
NURSING NURSING
SOMAJIGUDA SOMAJIGUDA
STUDENT PROFILE:

NAME OF THE TOPIC : GENETICS AND TERATOLOGY

NAME OF THE STUDENT : P. SONIYA
NAME OF COLLEGE : GOVERNMENT COLLEGE OF NURSING
TIME : 2 HRS
PLACE : MSC NURSING 1 STYEAR CLASS ROOM
GROUP : MSC NURSING 1 ST YEAR OBG
SPECIALITY
METHOD OF TEACHING : LECTURE AND DEMONSTRATION
AV AIDS : PPT,
NAME OF THE GUIDE : MRS R. ANITHA MADAM
General objectives: By the end of the class the group will be able to
understand about the topic genetics and teratology.
Specific objectives: by the end of class group will be able to:
 Know the terminology related to genetics and teratology.
 Define the term genetics, heredity, variations and teratology.
 List out the premammalian view of inheritance and mendalian inheritance.
 Enlist universal laws of inheritance.
 discuss human genetics.
 Classify chromosomes.
 Define pedigree chart.
 describe symbols of pedigree.
 Identify modes of inheritance: basic and unusual patterns of inheritance
 Define birth defects, list out the causes, common types, detection methods,
prevention strategies.
 Define genetic counselling, list out purposes, types, techniques of diagnosis,
and role of nurse.
 Define teratogenesis list out principles and types.
 Define mutagenesis list out mutagens and applications.
 List out recent research studies.
 Conclusion.
TERMINOLOGY:
Allele
An alternative form of a gene that occurs at the same locus on homologous
chromosomes, e.g., A, B, and O genes are alleles.
Amorph
A silent gene that does not produce a detectable product (antigen),
e.g., O genes in the ABO BGS.
Aneuploidy
Having an abnormal number of chromosomes, i.e., not an exact multiple of
the haploid number. For example, Downs syndrome (three #21
chromosomes) or Klinefelter syndrome (XXY males).
Anticodon
A sequence of three bases in tRNA that is complementary to a codon in
mRNA. Enables tRNA to sequence amino acids in the order specified by
mRNA.
Antithetical
Alternative forms of the same antigen produced by allelic genes, e.g., K and
k antigens in the Kell BGS or C and c antigens in the Rh BGS.
Autosome
A non-sex chromosome. Synonymous with somatic
chromosomes (chromosome pairs 1-22).
Balanced polymorphism
An equilibrium of two or more alleles that has remained constant over long
periods of time.
Barr body
The sex chromatin, the visible inactive X chromosome on the somatic cell
nuclear membrane.
Beneficial gene
A gene that confirms a trait that is advantageous to survival and that
increases in frequency, e.g., the Fy gene that produces the Fy(a-b-)
phenotype which makes West Africans resistant to certain types of malarial
parasites.
Chimera
An extremely rare person composed of cells derived from different zygotes.
Blood group chimerism is shown by mixed field agglutination when antigen
typing red cells. Chimerism can be caused by dizygotic twins exchanging
hematopoietic stem cells in utero and continuing to form blood cells that are
 genetically different, or by dispermic chimerism in which two separate
zygotes develop into one person.
Chromosome
Rod-shaped structures within the cell nucleus that carry genes encoded by
DNA.
Cis position
Genes in the cis position are on the same chromosome of a pair of
homologous chromosomes. Mainly relates to the Rh BGS, e.g., in the
genotype CDe/cde, D and C genes are in the cis position.
Cloned gene
A recombinant DNA molecule with the gene of interest. (Also see
recombinant DNA.)
Co-dominant
Genes are co-dominant if both alleles are expressed in the heterozygous
state, e.g., K and k genes in the Kell BGS.
Codon
A sequence of three bases in DNA or RNA that codes for a single amino
acid. Enables specific proteins to be made by specific genes.
Consanguinity
Having a common ancestor, i.e., being blood relatives. Mating between two
first cousins, for example, can be termed a consanguineous mating and is
indicated in a pedigree by a double bar between the two parents. Such
mating can result in an increased frequency of offspring who are
homozygous for a recessive autosomal trait possessed by both parents, e.g.
cystic fibrosis or the amorphic type of Rh null.
Crossing over
The exchange of genetic material between members of a pair of homologous
chromosomes. For example, if a mating between a male (MS/Ns) and a
female (MS/MS) results in an offspring who is MS/Ms, the recombinant child
has occurred due to crossing over in the father.
Deletion
An abnormality in which part of a chromosome (carrying genetic material) is
lost.
Deleted phenotype
The condition in which antigens that are normally present are missing, e.g.,
the Rh null phenotype in the Rh BGS. Deleted phenotypes can be caused by
inheritance of regulatory genes that do not allow functional (antigen-
producing) genes to make their products.
Diploid number of chromosomes
The number of chromosomes found in somatic cells, which in humans is 46.
Dizygotic twins
Twins produced from two separate ova that are separately fertilized, i.e.
fraternal twins. Only dizygotic twins can exhibit blood group chimerism
(shown by mixed field agglutination when antigen typing red cells).
DNA
Deoxyribonucleic acid. Composed of nucleic acids, these molecules encode
the genes that allow genetic information to be passed to offspring.
DNA polymerases
Enzymes that can synthesize new DNA strands using previously synthesized
DNA (or RNA) as a template.
DNA probe
A cloned DNA molecule labelled with a radioactive isotope (e.g., 32P or 35S)
or a nonisotopic label (e.g., biotin). Used in molecular genetics to identify
complementary DNA sequences by hybridizing to them.
Dominant gene
A gene is dominant if it is expressed when heterozygous but its allele is not,
e.g. in the Lewis system the Le gene is dominant (expressed in
both Le Le and Le le genotypes) and the le gene is recessive.
Functional genes
Genes that produce proteins, e.g., blood group genes that produce antigens.
Gamete
A reproductive sex cell (ovum or sperm) with the haploid number (23) of
chromosomes that results from meiosis.
Gene
A segment of a DNA molecule that codes for the synthesis of a single
polypeptide.
Gene flow
Changes in gene frequencies that occur over long periods of time due to
migration in which different populations interbreed. An example is the
transfer of genes between racial groups, e.g., the "white" genes of the Duffy
blood group system (Fya Fyb) have an increased frequency in U.S. blacks
compared to African blacks.
Gene interaction
The situation in which genes inherited at different loci interact to produce
red cell phenotypes, e.g., Le le genes interact with Hh and Se se genes to
produce the various Lewis red cell phenotypes.
Genome
Term used to denote the entire DNA sequence (gene content) of a gamete,
person, population, or species.
Genotype
 All of the alleles present at the locus (or closely linked loci) of a blood group
system, indicating chromosomal alignment if appropriate, e.g., AO in the
ABO BGS, CDe/cde in the Rh BGS, or MS/Ns in the MNSs BGS.
Genotypes are indicated by superscripts, underlining, or italics.
Haploid number of chromosomes
The number of chromosomes found in sex cells, which in humans is 23.
Hardy-Weinberg law
A law developed in 1908 independently by George Hardy (an English
mathematician) and Wilhelm Weinberg (a German physician) that is the
basis for calculations used in population genetics. The law is described by
the formula p2 + 2pg + q2 = 100%, where p is the frequency of one
allele, q is the frequency of the other, p2 and q2 are the homozygous
frequencies, and 2pg is the heterozygous frequency. The formula allows us
to calculate the frequencies of genes, phenotypes, and genotypes when the
frequency of a genetic trait is known.
Harmful gene
A gene that confirms a harmful trait such that it is reduced to a level at
which it is maintained only by recurrent mutation, e.g., the gene for
hemophilia A, which has a mutation rate of 1 in 10,000.
Hemizygous
Inheritance of an X-linked gene in males, e.g. the Xga gene or the gene for
hemophilia A is said to be hemizygous in males since they have only one X
chromosome.
Heterozygous
The situation in which allelic genes are different, e.g. the Kk genotype in the
Kell BGS or the Fya Fyb genotype in the Duffy BGS.
Homologous chromosomes
A matched pair of chromosomes, one from each parent, e.g., two #6
chromosomes.
Homozygous
The situation in which allelic genes are identical, e.g., the KK genotype or
the Fya Fya genotype.
HUGO
Acronym for Human Genome Organization, an international organization
conceived in 1988 to co-ordinate the Human Genome Project.
Human Genome Project
A worldwide project to map and sequence the human genome. The ultimate
goal is to produce the complete nucleotide sequence of every human
chromosome. (Also see HUGO.)
Immune response genes
 Name given to genes that appear to be able to control whether a person is
likely or unlikely to make red cell antibodies. Help explain why some
transfusion recipients are hyper-responders (make multiple alloantibodies)
and others, even when transfused with a very immunogenic antigen like D
from the Rh system, never produce antibodies. (About 30% of D-negative
people appear incapable of making anti-D.) The genes that regulate the
immune response may be linked to the genes of the major histocompatibility
complex (MHC) or may be the MHC genes themselves.
Index case
See proband.
Karyotype
A photomicrograph (photograph taken through a microscope) of all the
chromosomes in a person, arranged in standard classification (from #1
chromosomes through to the sex chromosomes).
Linkage
Genes are linked if they are on the same chromosome within a measurable
distance of each other and are normally inherited together, e.g., Lutheran and
Secretor genes are linked as are the Dd, Cc, Ee subloci in the Rh BGS.
Locus
The location of allelic genes on the chromosome, e.g., A, B, and O genes
occur at the ABO locus. (Plural = loci)
Lyon hypothesis
The hypothesis proposed by Mary Lyon in 1961-2 that in the somatic cells
of females one X chromosome is inactivated and becomes a Barr body.
Because the process is random, which X is inactivated is due to chance; once
inactivated, however, all of a cell's descendants will have the same inactive
X. The hypothesis explains how males with only a single dose of an X-
linked gene can have the same amount of genetic product as females with a
double dose of the X-linked gene.
Mapping of genes
A variety of processes that include discovering that a gene is linked to
another gene (which can serve as a marker for it), assigning genes to
particular chromosomes, assigning genes to specific regions on
chromosomes, and determining nucleotide sequences on chromosomes.
Meiosis
The type of cell division that occurs in sex cells by which gametes having
the haploid number of chromosomes are produced from diploid cells.
Messenger RNA (mRNA)
Type of RNA polymerase using DNA as a template. Contains the codons
that encompass the genetic codes to be translated into protein.
Mitosis
Cell division that results in the formation of two cells, each with the same
number of chromosomes as the parent cells, i.e., cell division that forms all
new cells except sex cells.
Modifying gene
A regulatory gene (usually at a different locus than blood group genes) that
in some way alters the expression of the blood group genes. Also called
suppressor genes.
Monozygotic twins
Twins derived from a single fertilized ovum, i.e., identical twins.
Mutation
A permanent inheritable change in a single gene (point mutation) that results
in the existence of two or more alleles occurring at the same locus. Blood
group polymorphism has been caused by mutations occurring over long
periods of time.
Nondisjunction
The failure of two members of a chromosome pair to disjoin during
anaphase. For example, an offspring with the AB/O genotype can be
produced if a group AB male mates with a group O female and
nondisjunction happens in the father.
Northern blot
A blotting method used to analyze and detect RNA by using a DNA probe
that will hybridize with its complementary RNA strand. Named for its
similarity to the Southern blot used to analyze DNA.
Nucleic acids
Polymers of phosphorylated nucleosides, the building blocks of DNA and
RNA.
Nucleoside
The building blocks of RNA and DNA. Compounds consisting of a purine
(adenine or guanine) or pyrimidine (thymine or cytosine) attached to ribose
(in RNA) or deoxyribose (in DNA) at the 11 carbon.
Nucleoside analogue
Synthetic nucleosides that are similar to nucleosides but differ at a key
location. When incorporated into DNA, they terminate DNA chains and thus
are useful as antiviral drugs. Examples are zidovudine (azidothymidine or
AZT) and dideoxyinosine (ddI) used to treat AIDS.
Operator
A short sequence of nucleotides that controls the adjacent structural
(functional) genes.
Operon
 A postulated unit of gene action that consists of an operator and the closely
linked functional genes it controls.
PCR
See polymerase chain reaction.
Pedigree
A diagram representing a family tree.
Phenotype
The antigens (traits) that result from those genes that are directly expressed
(can be directly antigen typed), e.g., group A in the ABO BGS or D+C+E-
c+e+ in the Rh BGS.
Plasmid
Extrachromosomal circular DNA in bacteria. Plasmids can independently
replicate and encode a product for drug resistance or some other advantage.
Used in molecular genetics as vectors for cloned segments of DNA.
Polymerase chain reaction
An in vitro method of amplifying DNA sequences hundreds of millions to
billions of times in a few hours. Developed in 1984-1985 by Mullis, Saiki, et
al.
Polymorphism
The existence of two or more different phenotypes resulting from two or
more alleles, each with an appreciable frequency. Most blood group systems
are polymorphic.
Polypeptides
Polymers of amino acids that form the building blocks of proteins.
Population genetics
The branch of genetics that deals with how genes are distributed in
populations and how gene and genotype frequencies stay constant or change.
Calculations are based on the Hardy-Weinberg law.
Proband
The family member whose phenotype leads to a family study. Also called an
index case.
Proposita
A female proband.
Propositus
A male proband.
Recessive
Genes are recessive if the phenotype that they code for is only expressed
when the genes are homozygous, e.g., le le genes, in the Lewis system or h
h genes in the ABO BGS.
Recombinant
 A person who has a new combination of genes not found together on the
chromosome in either parent, e.g., an MS/Ns offspring whose parents
are Ms/NS and MS/MS. A recombinant results from crossing over in one
parent.
Recombinant DNA
In molecular genetics, artificially made DNA composed of fragments of
DNA from different chromosomes (often from different species) that have
been joined together (spliced) by genetic engineering. For example,
healthcare workers are routinely vaccinated with a recombinant hepatitis B
vaccine made by inserting a piece of the hepatitis B virus genome (the part
that codes for the HBsAg) into yeast cells via a plasmid. The yeast cells then
produce a large amount of HBsAg, which is purified into the vaccine and
stimulates the production of protective anti-HBs antibodies.
Regulatory genes
In the operon model, genes that inhibit an operator gene so that it prevents
its functional genes from producing proteins.
Restriction endonucleases
DNA enzymes of bacterial origin that can cleave DNA at internal positions
on a strand because they recognize specific sequences (usually 4-6 base
pairs). The enzymes evolved in bacteria as defenses against the invasion of
foreign DNA in the form of viruses or plasmids and are used in molecular
genetics to chop up DNA at particular locations.
Restriction fragment length polymorphisms (RFLP)
Regions of DNA of varying lengths that can be cut out of DNA by
restriction endonucleases. Because the fragment lengths vary among
individuals, they are polymorphic and can be used as genetic markers.
Reverse transcriptase
An RNA-dependent DNA polymerase that synthesizes DNA from an RNA
template. Used by retroviruses like the human immunodeficiency virus
(HIV) to make proviral DNA from its RNA genome.
RFLP
See restriction fragment length polymorphism.
Ribosomal RNA (rRNA)
Type of RNA found in ribosomes, the site of protein synthesis in the
cytoplasm.
Ribosomes
Complexes of rRNA and protein in cytoplasm that serve as platforms for
translation for mRNA into protein.
RNA
Ribonucleic acid. Nucleic acids that are formed using DNA as a template.
Similar to DNA except has ribose in place of deoxyribose and uracil in place
of thymine. (Also see messenger RNA, ribosomal RNA, and transfer RNA.)
Sex chromosomes
The chromosomes that determine sex. XX in females and XY in males.
Sex-linked
An outdated term for genes on the X chromosome. Historically synonymous
for X-linked since, apart from genes essential for male sex determination,
the Y chromosome appears to have few recognized gene loci.
Somatic chromosome
A non-sex chromosome (soma=body). Synonym is autosome.
Southern blot
A blotting method developed in 1975 by E.M. Southern that detects
restriction enzyme-cleaved DNA by use of a labelled DNA probe that will
hybridize with its complementary DNA strand.
Structural genes
See functional genes.
Suppressor genes
See regulatory genes.
Syntenic
Genes are on the same chromosome but are not close enough for linkage to
be demonstrated.
Transcription
Synthesis of single-stranded RNA by RNA polymerase using DNA as a
template. The process in the nucleus whereby DNA is transcribed into
mRNA.
Transfer RNA (tRNA)
Type of RNA that facilitates translation of mRNA into protein. Contains
anticodons that provide the molecular link between the codons of mRNA
and the amino acid sequences of proteins.
Transient polymorphism
A temporary polymorphism in which an allele (harmful gene) is
disappearing or an allele (beneficial gene) is increasing in frequency.
Translation
The process of translating the codon sequence in mRNA into polypeptides
with the help of tRNA and ribosomes.
Trans position
 Genes in the trans position are on opposite chromosomes of a pair of
homologous chromosomes. In the genotype CDe/cde, for
example, D and c genes are in the trans position.
Western blot
An assay used to separate viral (and other) antigens and to identify
corresponding antibodies to the viral antigens. For example, the western blot
is a relatively specific and sensitive test for antibodies to HIV that is used as
a confirmatory test for sera that are repeatedly reactive by EIA (enzyme
immunoassay) screening tests. Named western blot as a joke due to its
similarity to the Southern blot and since its discoverers worked in the
western USA.
X-chromosome
The sex chromosome present in double dose in females (XX) and in single
dose in males (XY).
X-linked
Genes on the X chromosome, e.g., genes for haemophiliaA, haemophilia B,
and Xga blood group genes.
Y-chromosome
The sex chromosome present only in males (XY).
INTRODUCTION:
Genetics is a branch of biology concerned with the study of genes, genetic
variations and hereditary in organisms.
Father of genetics-Gregor Johann Mendel.
The term genetics was coined by Bateson in 1906.
Genetics is the study of principles and mechanisms of hereditary and variations.
Variations are the differences found in morphology, physiology, cytology and
behavioristic traits of an individual belonging to same species and appearing in
progeny.
Variations occur due to
a) Reshuffling of genes
b) Crossing over
c) Combining of chromosomes during gamete formation.
Heredity: it is the study of transfer of characters from parent to offspring from one
generation to the next.
The physical basis of heredity is gene whereas the chemical basis is dealt with
DNA.
Pre mendelian view
This type of inheritance deals with “theories of blending inheritance”. Which was
proposed by kolruter and Nuclin.
In this there will blending of the characters and not the sex and the colour of the
children i.e. blending of characters of two parents.
In most of the cases the progeny will be resembling the grandparents.
Mendelian inheritance:
Mendel was the first one to reveal the mystery of heredity by his interest in
breeding of garden peas.
Though his experiment results were read out in ‘natural history society of brunn’
he did not got any recognition throughout his life
After Mendel scientist T. H. MORGAN put forward the concept of genes in
heredity during 2nd world war later many scientists with their experiments lead
their pathway to the origin of molecular genetics.
Mendel was the 1st person to propose the transfer of characters from one generation
to the next i.e. Inheritance.
He was a son of farmer cultivating peas
Mendel was an Austrian monk worked on peas
Mendel considered 7 traits :
 Colour of flower
 Flower position
 Seed colour
 Seed texture
 Height
 Pod colour
 Pod appearance

Mendel conducted crossing experiment between true breeding plants for these 7
traits by emasculations and reciprocal crosses.
A cross between 2 parents differing in single trait is monohybrid cross.
A cross between 2 parents differing in 2 traits is dihybrid cross.

Based on his experiment Mendel proposed universal Laws of Inheritance.

1) The Law of Segregation: Each inherited trait is defined by a gene pair. Parental
genes are randomly separated to the sex cells so that sex cells contain only one
gene of the pair. Offspring therefore inherit one genetic allele from each parent
when sex cells unite in fertilization.
2) The Law of Independent Assortment: Genes for different traits are sorted
separately from one another so that the inheritance of one trait is not dependent on
the inheritance of another.
3) The Law of Dominance: An organism with alternate forms of a gene will
express the form that is dominant.

Human genetics deals with the variations between humans. These variations
are, in part, reflections of differences that exist at the DNA level.
Chromosome features:
(a) Chromatids: Metaphase chromosomes are divided longitudinally into two
sister chromatids.
(b) Centromere: The chromatids are held together at the centromere, or primary
constriction, which delineates the chromosome into a short arm (p) and a long arm
(q).
(c) Centromere position: Chromosomes are divided into three groups based on
centromere location.
1) Metacentric chromosomes: (such as chromosome 1), have a central
centromere.
2) Sub metacentric chromosomes: (such as chromosome 6), have a centromere
that is displaced from the center.
3) Acrocentric chromosomes: (such as chromosome 13), have a
centromere near one end.
It consists of 23 pairs of chromosomes: 22 homologous pairs of autosomes and one
pair of sex chromosomes.

The autosomes, by convention, are divided into seven groups:

 A (chromosomes 1 to 3),
 B (chromosomes 4 and 5),
 C (chromosomes 6 to 12),
 D (chromosomes 13 to 15),
 E (chromosomes 16 to 18),
 F (chromosomes 19 and 20),
 G (chromosomes 21 and 22).
The sex chromosomes are XX or XY.
Diagnostic cytogenetic analysis can be performed with metaphase or prometaphase
chromosomes obtained from rapidly dividing cells in tissue culture, or, in some
cases, directly from tissues with high mitotic activity.

A pedigree chart is a diagram that shows the occurrence and appearance

of phenotypes of a particular gene or organism and its ancestors from one
generation to the next, most commonly humans, show dogs, and race horses.
Genetic Defects and Mode of Inheritance
The genetic diseases may range from loss or gain of entire Chromosomes or large
chromosome segments (Chromosomal Abnormalities) to just change of a single
base pair within a gene (Single gene mutations).
A third type of genetic diseases is a process in which a disorder results of
interaction between one or more abnormal genes and environmental factors
(Multifactorial inheritance). I - Single Mutant Gene: Each single mutant gene will
exhibit one of 4 patterns of Mendelian inheritance:
There are five basic modes of inheritance for single-gene diseases:
 autosomal dominant,
 autosomal recessive,
 X-linked dominant,
 X-linked recessive, and
 mitochondrial.
Genetic heterogeneity is a common phenomenon with both single-gene diseases
and complex multi-factorial diseases.
Disease is said to be autosomal or X-linked depending on whether the mutant gene
is located on an autosome or X chromosome.
Also, it is classified as recessive when the one mutant gene cannot express the
disease, while dominant when only one mutant gene is sufficient to express the
disease.

Autosomal Dominant Pattern:

DEFINITION: In autosomal dominant disorders, one altered single copy of a gene
is enough to cause the disease
NUMBER OF AFFECTED ALLELES: Only one allele is needed from the
maternal or paternal side
CARRIER STATE: No carrier status
ONSET OF THE DISEASE: Late onset
DOMINANT/ RECESSIVE: Mutated copy of the gene (allele) is in dominant state
CHANCES OFAN AFFECTED CHILD: 50% chance of having an affected child
ng
PARENT'S STATUS: One parent is affected
EXAMPLES: Huntington disease, tuberous sclerosis. Myotonic dystrophy. and
neurofibromatosis

Autosomal Recessive Pattern:

DEFINITION: In autosomal recessive disorders, both altered copies of a gene are
needed to cause the disease
NUMBER OF AFFECTED ALLELES: two one allele is needed from the maternal
or paternal side
CARRIER STATE: Only when one allele is affected
ONSET OF THE DISEASE: early onset
DOMINANT/ RECESSIVE: Mutated copy of the gene (allele) is in recessive state
CHANCES OFAN AFFECTED CHILD: 25% chance of having an affected child
PARENT'S STATUS: One parent is unaffected
EXAMPLES: Sickle cell disease and cystic fibrosis.
X linked Dominant Inheritance Pattern
Definition: Mode of X linked genetic inheritance in which a dominant mutant gene
causes the disease
 In females a mutation in one of the two copies of the gene in each cell is
sufficient to cause the disorder.
 Occurrence is less common
 Mutant gene: a dominant gene on X chromosome
 More frequently occur in females
 Example diseases: Alpert syndrome, fragile X syndrome, Rett syndrome.

X linked recessive inheritance pattern

Definition: mode of X linked genetic inheritance in which one or two mutant gene
copies cause the disease
 In females a mutation would have to occur in both copies of the gene to
cause the disorder.
 Occurrence is more common
 Mutant gene: a recessive gene/genes on X chromosome
 More frequently occur in males
 Example diseases: hemophilia, Duchenne muscular dystrophy, ichthyosis.

Unusual patterns of inheritance

Types:
 Incomplete dominance.
 Co-dominance.
 Genetic linkage.
 Multiple alleles.
 Epistasis.
 Extranuclear inheritance.
 Polygenic traits.
Birth defects

Birth defects are typically classified as structural or functional and developmental.

Structural defects are when a specific body part is missing or malformed. The most
common structural defects are:

 heart defects
 cleft lip or palate, when there’s an opening or split in the lip or roof of the
mouth
 spina bifida, when the spinal cord doesn’t develop properly
 clubfoot, when the foot points inward instead of forward

Functional or developmental birth defects cause a body part or system not to work
properly. These often cause disabilities of intelligence or development. Functional
or developmental birth defects include metabolic defects, sensory problems, and
nervous system problems. Metabolic defects cause problems with the baby’s body
chemistry.

The most common types of functional or developmental birth defects include:

 Down syndrome, which causes delay in physical and mental development.

 sickle cell disease, which occurs when the red blood cells become
misshapen.
 cystic fibrosis, which damages the lungs and digestive system.
Genetic Counseling
Genetic counseling (G.C.) is defined as " an educational process that seeks to assist
affected and/or at risk individuals to understand the nature of a genetic disorder, its
transmission and the options available to them in management and family
planning.
G. C is an important form of preventive medicine. It is expensive but it is an
effective way of diminishing society burden of chronic disease, which is far more
expensive.
Purpose of genetic counselling
 Provide concrete, accurate information about inherited disorder.
 Reassure people who are concerned that their child may inherit a particular
disorder that the disorder will not occur.
 Allow people who are affected by inherited disease to make informed choice
about future reproduction.
 Educate people about inherited disorder and the process of inheritance.
 Offer support by skilled health care professionals to people who are affected
by genetic disorders.
Types of genetic counselling:
Prospective genetic counselling
 In this the genetic disorder has not yet expressed itself
 It is done is heterozygotic individuals to assess the probability of having a
child with genetic disorders
 If a person is identified as heterozygotic for a genetic condition, he/she
should be advised against marrying another heterozygotic individual as there
is increased risk of the trait expressing itself in the phenotype
Retrospective genetic counselling
 In this, the disease has already occurred in the family
 This is more commonly done compared to prospective genetic counselling
 This is because, people usually come for genetic counselling only after
having a child with congenital anomalies / mental retardation / inborn errors
of metabolism
 The interventions as a part of retrospective genetic counselling are:
 Contraception
 Sterilization
 Termination of pregnancy
Types
I - Premarital G.C.
1 - General advice
The chance of both parents carrying the same rare recessive gene is greater if they
are related. The likelihood of the patient's disease being recessively inherited is
thus increased in the presence of consanguinity.
2 - Specific advice:
Premarital screening carrier cases of some common recessive disorder e.g.
thalassemia, is an important task. A premarital advice for those carriers may lead to
prevention of such incurable diseases.
II - Preconception G.C.
1 - General advice:
The increasing risk of trisomy with increasing parental age must be put in mind.
2 - Specific advice:
 Parents with previous baby with definite genetic disorder must be informed about
the nature of this disease, the risk of recurrence and the available options, e.g.
family planning if already have children (in the case of autosomal
recessive disorder).
Ill – Post conception G.C.
1 - General advice:
Avoidance of any teratogens e.g., radiation, drugs and infections during
pregnancy.
2 - Special advice:
Pregnancy at risk of genetic disorder gets benefit of prenatal diagnosis.
This may include ultrasound, amniocentesis and chorionic villus
sampling and fetal blood sampling.
After a definite diagnosis of a genetic disorder, some disease may get benefit from
intrauterine treatment e.g. hydrocephalus.
 On the other hand genetic indication for interrupting pregnancy is still
controversial (for religious causes) e.g. trisomy.
IV - Neonatal Screening
1 - General advice
Universal neonatal screening is helpful for detection of common genetic
disorder in which early detection is mandatory e.g. hypothyroidism.
2 - Specific advice
The high-risk newborn infant for specific genetic disease must be screened early
for this disease, e.g. developmental dislocation of the hip.

Prenatal Diagnosis
Definition
1. Prenatal diagnosis is the process that aims at reaching a diagnosis regarding the
presence or absence as well as the nature of a possible genetic or dysmorphic
disorder present in a fetus.
2. Prenatal diagnosis allows the detection of birth defects and genetic disorders
before delivery giving the parents the option of pregnancy termination or
additional time for emotional adjustment.
Indications
1. Prenatal diagnosis is indicated in cases with increased risk of birth defect or
genetic disease such as:
1. Women >35 years (risk of Down syndrome)
2. Elevated maternal serum alpha fetoprotein (risk of open defect, e.g. neural tube
defects)
3. Low maternal serum alpha fetoprotein (risk of Down syndrome)
4. Prior history of autosomal trisomy (risk of trisomy)
5. Parents with balanced chromosomal translocation (risk of unbalanced
karyotype). Balanced translocation means translocation of a part of a chromosome
to another chromosome within the same cell so that the genetic material of the
whole cell is not changed.
6. Family history of genetic disorder or carrier parent (risk of specific disorder in
family)
7. Family history of isolated structural defect (risk of same structural defect).

Techniques used in prenatal diagnosis

1-Maternal serum alpha fetoprotein (AFP)
2-Fetal ultrasound
3-Amniocentesis
4-Chorionic villus sampling (CVS)
5-Percutaneous umbilical blood sampling (PUBS)
6-Fetoscopy Trisomy 21
Mosiac: Normal Mosiac (M or F)
Slightly increased Depends upon degree of mosiacism
Role of nurse in genetic counselling:
 Guiding women and married couple.
 Helping parents make decision in regard to normal prenatal diagnostic
results
 Assist parents who have had a child with a birth defect
 Provide support to help the family deal with emotional impact of birth
defects.
 Co ordinate and collaborate for sevices
Teratogenesis and Mutagenesis
HISTORY
Teratology, the study of environment-induced malformations, began as a modern
science in the 1930s, with the publication of a set of experiments in which pregnant
pigs were fed a diet deficient in vitamin A.
1 The resulting abnormalities in the offspring demonstrated that mammalian
development, by its residence within the mother, was not as protected as was
previously believed. In fact, the results of these experiments showed that relatively
simple alterations in the environment could have devastating effects on the
embryo. The susceptibility of mammalian embryos to toxicity from xenobiotic
agents was demonstrated in a series of studies in experimental animals with
congeners of biologically important molecules, such as the amino acid mimic
azaserine.
2 A human counterpart to these experiments was reported in the 1950s, when
aminopterin was used in some human pregnancies to produce abortion. Several
malformed children were born after the drug failed to terminate the pregnancies.
3 The thalidomide episode of the early 1960s increased our understanding of
developmental toxicology by providing an example of an agent that produced
minimal toxicity to adults but a high degree of toxicity for the embryo.
Such selective embryotoxicity remains the key element of many experiments
evaluating the toxic potential of drugs used during pregnancy.
It was during the 1960s that regulatory agencies, including the Food and Drug
Administration in the United States, developed requirements for testing drugs in
animals before approval for marketing. Drug studies were required to use doses
high enough to cause maternal toxicity in order to add confidence that a
biologically relevant dose for that.
Modern developmental toxicity studies in animals are performed with an
understanding of how each species handles the drug. With the use of current
animal testing protocols, drugs that could produce birth defects in human beings
should be able to be identified.
 Both teratogens and mutagens can cause alterations in the structure and
functioning of the body, but the mechanisms differ.
Teratogens cause damage by altering embryonic or fetal development directly.
Mutagens cause changes within the genetic material that may lead to inherited
disease if the germ cells are affected or to cancer if somatic cells are involved.

PRINCIPLES OF TERATOLOGY
Principle 1: Susceptibility to teratogenesis depends on the genotype of the
conceptus and the manner in which it interacts with the environment
Principle 2: Susceptibility to a teratogenic agent varies with the developmental
stage at which the exposure occurs
Principle 3: Teratogenic agents act in specific ways (mechanisms) on developing
cells and tissues to initiate abnormal embryogenesis (pathogenesis)
Principle 4: The final manifestations of abnormal development are death,
malformation, growth retardation, and functional disorder
Principle 5: Access of an adverse environmental agent to developing tissues
depends on the nature of the agent (influences)
Principle 6: The manifestations of deviant development increase in degree as
dosage increases from the no-effect to the lethal level

TERATOGENESIS

A teratogen is an agent that can produce a permanent alteration of structure or

function in an organism after exposure during embryonic or fetal life.
Teratogens include environmental factors, medications, drugs of abuse, and
occupational chemicals. Clinical teratology is concerned with the following:
1. The relationship between the anomalies in a child and teratogenic exposure.
2. The risk of anomalies for a child of a woman who has been exposed to a
teratogen.
3. The risks to a pregnant woman of treatment or exposure to a given agent.

Principles of clinical teratology:

Teratogens act at vulnerable periods of embryogenesis and fetal development.
  In general, the embryo is most sensitive to damage between 2 and 10 weeks
after conception (4 to 12 weeks after the beginning of the last menstrual
period). During this time, most structures and organs are differentiating and
forming. Each structure has its own period of greatest sensitivity within this
time.
 The first 2 weeks after conception is generally considered to be a period that
is resistant to the induction of malformations by teratogens.
 At this point, the embryo consists of few cells, and damage is usually either
repaired completely or results in death of the embryo.
 By 10 weeks after conception, most structures in the embryo have been
formed, so malformations are unlikely to be produced by subsequent
exposures.
Teratogenic factors are thought to be responsible for about 10% of all congenital
anomalies. These factors fall into several groups:
1) Maternal metabolic imbalance: as children of women with insulin-dependent
diabetes mellitus have a risk of congenital anomalies that is two to three times
greater than that of the general population.
2) Infectious agents can involve the embryo or fetus transplacentally. For
example:
Congenital toxoplasmosis (may be asymptornatic or present with a variety of
abnormalities. Severely affected infants may exhibit chorioretinitis, hydrocephaly
or microcephaly, intracranial calcification, and mental retardation.
Rubella (German measles) embryopathy produces fetal growth retardation,
hepatosplenomegaly, purpura, jaundice, microcephaly, cataracts, deafness,
congenital heart disease, and mental retardation.
Congenital cytornegalovirus (CMV) infection may produce fetal growth
retardation, hepatosplenornegaly, hemolytic anemia, purpura, jaundice, intracranial
calcification, and microcephaly.
3) Ionizing radiation causes DNA damage and can injure the
developing embryo.
4) Environmental agents and occupational chemicals:
1. Hyperthermia, regardless of cause, that produces sustained
elevation of maternal body temperature to levels substantially
above normal (e.g., 40 ºC)
2. Lead
5) Drugs of abuse
(1) Alcohol: Classic fetal alcohol syndrome occurs among the
children of women with chronic, severe alcoholism during
pregnancy.
(2) Cocaine: Maternal use of cocaine during pregnancy has been
associated with placental abruption and the occurrence of
vascular disruptions such as encephaloclastic lesions in the fetus.
(3) Medications:
1. Thalidomide exposure in the first trimester of gestation may
produce limb reduction defects, facial malformations, and
other congenital anomalies.
2. Aminopterin and other cytotoxic drugs kill rapidly growing
cells in the fetus and cause growth deficiency and a variety
of other anomalies.
3. An increased rate of congenital anomalies is observed
among the children of epileptic women treated with
anticonvulsant medications during pregnancy.

MUTAGENESIS
Definition: Mutagenesis is the process by which an organism's deoxyribonucleic
acids (DNA) change, resulting in a gene mutation. A mutation is a permanent and
heritable change in genetic material, which can result in altered protein function
and phenotypic changes.
A mutagen is an agent that can alter the DNA or chromosomes.
1. While teratogens act only during embryonic or fetal development, mutagens
may act at any time of life. Thus, mutations may occur in the gamete, zygote,
embryo, fetus, child, or adult.
2. Teratogens affect the development of a tissue, organ, or structure. In contrast, a
mutation always affects a single cell.
a) If this single cell is a germ cell, the mutation may be transmitted to subsequent
generations.
b) If a single cell in a very early embryo sustains a mutation, many tissues of the
embryo (including the germ cells) may be affected as embryogenesis progresses.
c) If a single cell in an embryo, fetus, child, or adult sustains a mutation; only cells
derived from the mutated cell will carry the mutation. Most cells in the individual
will not contain the mutation.

Applications:
 rDNA technology.
 Genetical modification of organisms and plants.

Recent researches:
1.an article from European journal of medical genetics in June 2021 after revising
in January 2021 development of research in the field of craniosynostosis from
a bibliometric standpoint. Craniosynostosis is a malformation occurring during the
early development of the skull, when one or more of the sutures close too early,
causing problems with normal brain and skull growth. Research in this field has
developed from early clinical case descriptions, to genetic discoveries responsible
for the occurring malformations and onwards to developing sophisticated surgical
treatment.
By
T. Elarjani, O.T. Almutairi, M. Alhussinan, A. Alturkistani, F.S. Alotaibi, M. Bafa
quh, et al.

2. GENETIC SUSCEPTIBILITY TO DRUG TERATOGENICITY

PUBLISHED ONLINE 2021 APR 27 IN JOURNAL FRONTIERS IN GENETICS ,
AUTHOR JULIA DO AMARAL GOMES
In summary, this systematic review identified 29 studies on human genetic
variation associated with the teratogenesis of several drugs. Antidepressants,
AEDs, glucocorticoids, and thalidomide were the most investigated drugs. The
most convincing findings were genetic variants in SLC6A4, MTHFR,
and NR3C1 being associated with drug teratogenicity from antidepressants, AEDs,
and glucocorticoids, respectively. Future studies on genetic teratology should aim
to consider the biological pathways and molecular mechanisms of teratogens more
broadly, and take into consideration the complexity of the multifactorial
teratogenic process. This approach requires increased sample sizes, the application
of genome-wide approaches, and international funding initiatives. To translate the
research into the clinic, application of novel methodologies for the collection and
examination of fetal DNA is encouraged, as well as the use of machine learning
methods and implementation of multidisciplinary teams. Taken together, these
efforts may ultimately promote early interventions and possibly minimize the
teratogenic impact of maternal drug use during pregnancy on the fetus

Conclusion:
A teratogen is any plant, food, nutritional state, or physical agent that can
compromise normal fetal development and result in the production of a congenital
mal-formation. Teratogenesis, in its simplest terms, is the destruction of a critical
number of cells in excess of which the fetus is able to restore by later proliferation.
In considering the effects of drugs on pregnancy, it is important to remember the 6
principles of teratology: genetic susceptibility, development stage, mechanisms,
end points, access, and dose response. Keeping these principles in mind will
facilitate critical review of the literature that is relevant to pregnancy management.