Aneuploid: A haploid gamete or diploid cell lacking the expected number of chromosomes (n or 2n)
Translocation: Following chromosomal breakage, material may be exchanged between two or more chromosomes. When no genetic material is lost, the translocation is balanced. Translocations may be reciprocal or robertsonian (acrocentric chromosomes: chromosomes 13,14,15,21,22).
Single gene: The DNA sequence encoding a single protein.
Mendelian Inheritance: Genetic traits that follow the Mendelian laws of segregation and independent assortment.
Multifactorial / polygenic: A combination of genetic and environmental factors must be invoked for anomalies whose recurrence risks are greater than the general population but less than that expected on the basis of a single recessive or dominant gene (25% and 50% respectively)
Polymerase chain reaction (PCR): Amplification of short sequences (up to 2kb) of DNA without the need for cloning. This method is based on the use of DNA primers that are complementary to sequences on either side of the DNA of interest. Approximately 35 cycles of denaturation (95ÉC), primer annealing (60ÉC), and extension (72ÉC) are then performed.
Genetic amniocentesis: The prenatal diagnostic procedure involving a needle puncture into the amniotic sac and obtaining amniotic fluid which contains cells of fetal origin. These cells can then either be used directly for fetal DNA analysis or cultured for fetal karyotype.
Percutaneous umbilical cord blood sampling (PUBS): The prenatal diagnostic procedure involving a needle puncture into the fetal umbilical blood vessels and obtaining fetal blood. The fetal blood then may be used directly for fetal DNA analysis, cultured for fetal karyotype, a fetal blood count, or assessment of fetal acid base status.
American College of Obstetricians and Gynecologists (A.C.O.G.) recommendations. 21.4% of couples will show at least one positive response, with 7.8% requiring formal genetic counseling. Advanced maternal age is the most common indication for further testing.
The genetic history
Inquire about the health status of 1st, 2nd, and 3rd degree relatives.
Record abnormal reproductive outcomes such as repetitive spontaneous miscarriage, stillbirths, and anomalous fetuses.
Record maternal and paternal drug exposure.
Record maternal and paternal ages.
Record maternal and paternal ethnic origins.
Principles and prerequisites of genetic screening
Screening programs versus case detection programs
One does not expect to detect all affected cases in a given population.
Establishing technical feasibility for screening a given disorder alone does not justify screening.
Capacity to alter clinical management
Reliable means of assessment
Capacity to handle problems
Specific indications for heterozygote genetic screening
The trait, the incidence of which usually 1 / 1000 live births, usually involves a single organ system or embryologically related organ systems.
The frequency of similarly affected cotwins is higher among monozygotic than dizygotic twins.
Unlike mendelian inheritance, the recurrence risk increases after more than one progeny is affected. The risk rarely approaches the 25% expected for recessive traits or the 50% expected for dominant traits.
The more serious the defect, the higher the recurrence risk. Bilateral cleft palate carries a higher recurrence risk than unilateral cleft palate.
If the trait occurs more frequently among members of one sex, the risk for relatives is higher if the proband (index case) is of the less frequently affected case. Pyloric stenosis occurs more frequently in males; thus, the recurrence risk is higher if the proband is female.
As the degree of relation decreases, the recurrence risks for relatives decreases more rapidly than that observed for autosomal dominant traits.
the family history, reproductive outcomes, maternal and paternal ages, maternal and paternal ethnic origins, and drug exposures .
Be familiar with common genetic syndromes and teratogens.
There exist a number of prenatal diagnostic procedures, amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, and fetoscopy, that have their indications, advantages, and disadvantages.
Be familiar with advancing molecular technology and its utility in the clinical setting. It is our responsibility as physicians to keep up with rapidly advancing diagnostic techniques. Techniques such as FISH, isolation of fetal cells in maternal circulation, and fetal stem cell transplantation are in our patients near future.