How many chromosomes are there in normal human cells?

Chromosomally normal human somatic cells contain 46 chromosomes (22 pairs of autosomes and 1 pair of gonosomes) (Figure 1). Normal gamete cells contain half this number that is 23 chromosomes (22 autosomes and 1 gonosome).

Figure 1: Normal male karyotype (46,XY)

Which methods are used for chromosomal analysis?

Cytogenetic methods are used for the numerical and structural analysis of chromosomes. Short and long culturing techniques can be used for karyotyping the cells. 

What samples are needed from the patient for chromosomal analysis?

Cytogenetic analysis can be applied to several kinds of samples:

• Peripheral Blood
• Fetal Blood (Cord blood)
• Amniotic Fluid
• Chorionic Villi
• Abortus Material
• Skin Samples

What is prenatal diagnosis (PND)?

Prenatal diagnosis, or prenatal screening, is testing for chromosomal abnormalities or diseases in a fetus before it is born. The aim is to detect chromosomal abnormalities such as Down Syndrome (Trisomy 21), Edwards Syndrome (Trisomy 18), and Patau Syndrome (Trisomy 13).

There are three methods of prenatal diagnosis: chorionic villus sampling (CVS), amniosynthesis and cordosynthesis (Figure 2).

Figure 2: In prenatal and postnatal diagnosis, the aim is to achieve best quality (band resolution) metahaphase cells for karyotype analysis.

Under what circumstances is prenatal diagnosis advisable?

If one or more of the following have been diagnosed during pregnancy:

• Abnormal ultrasound findings
• Abnormal trimester test
• Abnormal triple test

If either partner

• is the carrier of a chromosomal rearrangement
• is the carrier of an inherited disorder
• has gonadal mosaicism

If the female partner

• is of advanced maternal age
• has a history of a chromosomally abnormal fetus
• has been experiencing recurrent pregnancy losses 

What is Chorionic Villus Sampling (CVS) and when it can be performed?

During CVS, samples of trophoblast cells and chorionic villi are withdrawn transabdominally or transcervically, depending upon placental and uterine position. Chorionic Villus Sampling (CVS) can be performed between weeks11 and14 weeks of gestation.

What is Amniosynthesis and when it can be performed?

Under ultrasound guidance, a needle is inserted through the mother’s abdomen and approximately 20ml of amniotic fluid is withdrawn. Amniosynthesis can be performed from week 14 and usually up to about 20 weeks.

What is Cordosynthesis and when it can be performed?

Cordosynthesis is performed after 18 gestational weeks.  Under ultrasound guidance, a needle is inserted through the mother’s abdomen to obtain fetal blood from the umbilical vein.

For what type of genetic disorders can PND be performed?

Prenatal genetic diagnosis can also be performed for single gene disorders such as thalassemia, sickle cell anemia, cystic fibrosis, and fragile x syndrome. For these conditions, molecular analysis methods are used. In the case of an autosomal recessive disease, when both parents carry the same autosomal recessive disorder the fetus has a 25% risk of being affected. However, for autosomal dominant disorders, the risk of the fetus being affected is 50%. (Figure 2B)

What is Postnatal Genetic Diagnosis?

Postnatal genetic diagnosis is the analysis of chromosomes usually in peripheral blood samples. It aims to identify whether there are any karyotipic abnormalities.

When is it advisable?

Postnatal genetic diagnosis is mainly carried out for couples with

• Repeated IVF failures
• Recurrent pregnancy losses
• Abnormal fetus history
• Severe male factor infertility
• Family history of chromosomal rearrangement
• Family history of genetic disease (monogenic disorders)

Karyotype analysis can also be performed for children with dismorphic features or suspected conditions such as microdeletions or an unbalanced chromosomal rearrangement.

When is screening advisable?

Couples with a family history of a genetic disorder, or chromosomal abnormalities are strongly advised to be screened for this condition before planning a pregnancy.