Genetics In Reproductive

System
dr. Rahma Ayu Larasati, M.Biomed
 Introduction

• Your genome is the operating manual containing all

the instructions that helped you develop from a
single cell into the person you are today

• It guides your growth, helps your organs to do their

jobs, and repairs itself when it becomes damaged
Introducing Genes
• Genes  the unit of heredity, the sets of
biochemical instructions that tell cells, how to manufacture
certain proteins which determine inherited traits
• DNA  Deoxyribonucleic acid; the molecule whose
building block sequence encodes the information that a
cell uses to construct a particular protein
DNA Molecule
 CENTRAL DOGMA

PROTEINS
(active cell machinery)
Genetic Diseases

Single Gene Disease

Chromosomal Aberration

Multifactorial
Genetics Diseases and Pregnancy

• Individuals with Risk Factors due to Known Genetic Conditions

• Couples with Genetic Risk Factors Based on Specific Family History
• Couples with Ethnicity-Based Genetic Risk Factors
• Couples with Risk Factors
Individuals with Risk Factors due to Known Genetic Conditions

• Spesific Recommendations before and after conception

• Spesific treatment pre and post-natal
• Multidisciplinary management of pregnancy in women with genetic
disorders is recommended
• Example :
• increasing folate for Sickle Cell Disease patients
• women with phenylketonuria (PKU) should maintain low
phenylalanine diets prior to conception
Couples with Genetic Risk Factors Based on Specific Family History

• offering of testing for at least the person with affected relatives.

• If the person is found to have inherited a gene that could cause
the disorder in their children, their partner could be tested in
order to quantify the overall risk.
•  Carrier testing
Couples with Ethnicity-Based Genetic Risk Factors

• Couples at risk for any ethnicity-based conditions should be

offered preconception counseling about the risks of that condition
to future pregnancies.
• Screening and/or testing should be offered based on couples’
preferences.
Chromosomal Aberration
Fertilization = Conception
Fertilization is the fusion of the nucleus of a male gamet with the nucleus of a female
gamete. In humans, each gamete has half the number of the total 46 chromosomes that
the body requires. The 23 chromosomes within a gamet are referred to as a haploid.
Causes Of Chromosomal Abnormality

Anaphase Lag

Non-Disjunction
Anaphase Lag

• Occurs During anaphase

• Is where one chromosome fails to migrate to the pole of the spindle
• That chromosome then fails to be enclosed by the new nuclear envelope
• Chromosome is lost and gets degraded
• Results in 1x normal cell + 1x cell with a missing/extra chromosome
• Leads to monosomies & trisomies
Chromosome Mis-Segregation (Nondisjunction)

• Chromosomes aren’t divided equally among the gametes

• Results in either: gametes with extra or missing chromosomes
• If such gametes are fertilized → monosomies & trisomies
Non-disjunction in Meiosis
Risk Factors

• Exposure to drugs or certain infections

• Folic acid deficiency
• Multiple pregnancy (twins or more)
• Past pregnancy that involved a congenital abnormality
• Pre-pregnancy health condition, such as diabetes
• Pregnancy over the age of 35
• Recreational drug use
• Smoking
How to detect genetic disorder In Pregnancy?
 Anamnesis

• All women considering pregnancy should have a screening history in

the preconception visit. Providers should ask about risks to pregnancy
based on maternal age, maternal and paternal medical conditions,
obstetric history, and family history.
• Ideally, a three-generation family medical history should be obtained for
both members of the couple with the goal of identifying known genetic
disorders, congenital malformations, developmental delay/mental
retardation, and ethnicity
Details from personal or family history that should prompt further
counseling
Antenatal Ultrasound Scan

• the best time to do it is between 18- 22 weeks of

gestation.
• Soft markers for birth defect: Echogenic
intracardiac foci, echogenic bowel, and shortened
long bones (humerus or femur)
• Approximately 95% of fetuses with trisomy 18 or
trisomy 13 will have some feature identified on an
anatomy scan,
Maternal Serum Screening
HCG
• Human Chorionic Gonadotropin
• 5–20 mlU/ml

PPPA pregnancy-associated plasma protein-A

• PAPP-A is a large glycoprotein produced by the placenta and decidua thought to
have several functions, including prevention of recognition of the fetus by the
maternal immune system, matrix mineralization, and angiogenesis.
INHIBIN
• Formed in placenta during placental development
Cytogenetics Study

• Cytogenetics is the study of the structure and properties of chromosomes,

their behaviour during somatic cell division during growth and
development (mitosis), and germ cell division during reproduction
(meiosis), as well as their influence on phenotype. Cytogenetics also
includes the study of factors that cause chromosomal changes
• Cytogenetics is the study of chromosomes using light microscopy.
Chromosomal analysis is done by growing human cells in tissue culture,
chemically inhibiting mitosis, and staining, observing, photographing,
sorting, and counting the chromosomes.
Chromosome structure

• Chromosomes are thread-like structures

located inside the nucleus of animal and plant
cells.
• Each chromosome is made of protein and a
single molecule of deoxyribonucleic acid
(DNA). Passed from parents to offspring, DNA
contains the specific instructions that make
each type of living creature unique.
• The unique structure of chromosomes keeps
DNA tightly wrapped around spool-like
proteins, called histones. Without such
packaging, DNA molecules would be too long
to fit inside cells.
History

• It was the Swiss botanist Nageli who first described thread-like structures
in the nuclei of plant cells in the 1840s, and what he called “transitory
cytoblasts” are now known as chromosomes.
• Later, in 1888, Waldeyer coined the term “chromosome” after staining
techniques had been developed to make them more discernible (chromos
= Greek for colour; soma = Greek for body).
Indications of Cytogenetic studies
Prenatal

• Abnormal maternal serum screening (first or second trimester)

• Abnormal cell free DNA testing ( cfDNA ), non invasive prenatal
testing (NIPT)/screening (NIPS)
• Abnormal ultrasound findings: cystic hygromas hydrops , cardiac
defects, other malformations, IUGR, etc.
• Advanced maternal age (AMA), generally ≥ 35 yrs
• Parental or familial chromosome/genomic abnormality
Postnatal, childhood growth and development

• Perinatal/newborn: Birth defects, malformations,

• dysmorphisms, ambiguous genitalia
• Growth: failure to thrive, growth delay, short stature
• Developmental delay (fine and gross motor, speech)
• Cognitive: intellectual disability, learning disability
• Neurological: hypotonia, seizures, ataxia
• Behavioral: autism, OCD, psychiatric illness
Origin of sample

Postnatal
• Peripheral blood, buccal swab, skin biopsy

Prenatal
• Amniotic fluid, chorionic villus sampling, fetal
tissues
Sampling Tehniques-
Prenatal Genetic Testing
Cytogenetic Techniques

Fluorescent in
Multiplex-FISH
situ
Karyotyping (M-FISH)
hybridization
(FISH)

Comparative
Spectral
Genomic
Karyotyping
Hybridization
(SKY)
(CGH)
Chromosome banding-Karyotype

• Chromosome banding methods are either based on staining

chromosomes with a dye or on assaying for a particular function. The
most common methods of dyebased chromosome banding are G-
(Giemsa), R-(reverse), C-(centromere) and Q-(quinacrine) banding.
• Chromosome analysis, also called a karyotype, is considered the gold
standard for diagnosing aneuploidy.
• It provides information of normalcy, identification of sites of
chromosome breaks and alterations, and location of specific genes
When chromosome becomes viable?

• Chromosomes are not visible under the light microscope in non-

dividing (interphase) cells.
• As the cell begins to divide, the threads of chromatin (DNA-protein
complex) in the nucleus begin to condense into multiple levels of
coiled structures recognizable as chromosomes.
• At metaphase the chromosomes are at their most condensed state,
with spindle fibers attaching to the area of the centromere called
the kinetochore, forming pole-chromosome fibers.
• The addition of colchicines to arrest cells in metaphase and the
use of hypotonic solution to obtain better chromosome spreads
Karyotype

Based on size
and shapes
Fluorescent in situ hybridization (FISH)

• a method to visualise chromosomes using fluorescent-labelled

probes.
• Because FISH is done on interphase cells, results can be available in one to
two days. This can be very helpful in reducing patient anxiety; however, the
patient needs to be reminded that these are just preliminary results,
• Using FISH, cytogeneticists can detect chromosomal abnormalities
that involve small segments of DNA if their probe is situated
• The technique relies on exposing chromosomes to a small DNA
sequence called a probe that has a fluorescent molecule attached
to it.
• Sepasang Suami Istri sudah menikah 5 tahun dan belum dikaruniai
anak. Ibu Riwayat keguguran 2 kali. Keguguran dialami usia
kehamilan 5 minggu dan 6 minggu. Sang ibu diketahui memiliki
Riwayat penyakit
• Preimplantation genetic testing.