GENETIC ABNORMALITIES

Prenatal Diagnosis of Genetic Abnormalities

Fromal Outline

Prenatal Diagnosis of Genetic Abnormalities

Introduction

Discussion

Polymerase Chain Reaction

Direct Detection Methods by DNA Sequencing

Indirect Detection Methods

Polymorphic Markers and Molecular Diagnosis

Molecular Analysis of Genetic Alterations

Southern Blotting

Florescence in Situ Hybridization

Array Based Comparative Genomic Hybridization

Epigenetic Alterations

RNA Analysis

Prenatal Diagnosis of Genetic Abnormalities

Introduction

Prenatal genetic analysis is performed whenever a patient is cytogenetically at risk for abnormal progeny. It is performed on material obtained by amniocentesis, chorionic villus biopsy material or umbilical cord blood samples (Robbins & Cortan, 2010). There are some significant indications require the procedure. They are as follows:

Advanced age of either of the parents, especially the mother.

Parents who are the carrier of translocations such as balanced reciprocal, robertsonian or inversions.

Those who have a previous child with genetic alteration.

A fetus detected with abnormalities, through ultrasound.

A parent being the carrier of X-linked alterations.

Altered levels of fetal proteins such as, AFP, Beta-HCG and estriol and so on.

This led us to a beneficial prognosis of genetic alterations. Following are some of the procedures followed to detect such alterations in human genomes, beneficial for human use (Epstein & Golbus, 1978).

Discussion

Polymerase Chain Reaction

The procedure involves exponential amplification of DNA. This is now being widely used procedure for the molecular diagnosis of human disorders. Using appropriate DNA polymerases and thermal cycling, the DNA is amplified between the two primer sites. Identification of an abnormal sequence can be seen (Robbins & Cortan, 2010).

Direct Detection Methods by DNA Sequencing

Sequenced DNA is obtained and compared with a normal sequence so that mutations can be identified. Many of the mendelian disorders have been identified and definitively diagnosed of mutated genes by this procedure. Recessive inheritance is mostly associated with a limited number of recurrent mutations, for instance, cystic fibrosis, whereas dominant inheritance can have many of them. The procedure is very difficult and costly. For example, Duchenne muscular dystrophy has an associated gene with seventy nine exons, the one in marfan syndromes, the FBN1 has sixty five exons; sequencing of such genes is quiet expensive with current methodologies. Some other difficulties are detection of insignificant alterations, which are not pathogenic. Quick developing technology will be soon able to make these applications feasible to use in routine diagnosis. One such throughput technology is hybridization on microarrays of oligonucleotides. The procedure involves labeling the samples with fluorescent dyes and then hybridizing the targets. If mutation has occurred, it will cause hybridization at the complementary mutant oligonucleotide. After this, computerized algorithm are used to decode the sequence of DNA on the chip, this helps identify the potential mutations rapidly. One more recently introduced technology is the next generation sequencing. This procedure involves PCR performance in an oil emulsion (Robbins & Cortan, 2010).

Indirect Detection Methods

They are less costly and highly effective methods. Some good examples of indirect detection method are as follows:

One such method is digesting DNA with restriction enzymes that recognize and cut the target at specific sites. If the mutation is there at a restriction site, then DNA is first amplified and then digested. As the mutation effects a restriction site, both ...