Chromosomal Microarray Analysis: Pros and Cons

Chromosomal Microarray Analysis: Pros and Cons

Since the 1960s, the traditional way of screening for prenatal genetic disorders was through amniocentesis, an invasive procedure, which slightly increases the risk of miscarriage. A new method of genetic testing, called chromosomal microarray analysis, can detect submicroscopic genetic anomalies that other tests can not find. In this method, fetal DNA is obtained through a sample of a pregnant woman's blood. This technology is believed to be safer, faster and more accurate than the traditional, invasive test.

While there are many benefits to this more efficient prenatal genetic screening method, skeptics worry that babies will be born with a "syndrome label." Prior to this new technology, in 2005 in Mississauga, Ontario, at twenty-one weeks pregnant, the trisomy 13 disorder was detected in Barbara Farlow's unborn daughter. When Ms. Farlow's daughter, Annie, was about three months old, she suffered a respiratory attack and was admitted into the hospital. Annie died within 24 hours and the official cause was "complications of trisomy 13." However, Ms. Farlow and her husband still do not know all of the details, despite years of inquiry. They did find out, though, that a do-not-resuscitate order was issued by someone without their consent. They believe that the results of the prenatal genetic testing ultimately determined her fate and that "she was treated as a syndrome. She wasn't treated as a child."

Advocates for the new test say expectant parents can never be too informed and that more knowledge empowers people to make better choices. Other points made are that the test can be performed earlier than amniocentesis and that it provides the maximum amount of information about a fetus, allowing a prospective parent to either terminate the pregnancy or prepare for a child with disabilities. Microarray testing has already been used extensively as a diagnostic tool in pediatrics. When used to identify the genetic roots of mental retardation in children, for instance, it has proven twice as effective as conventional techniques. Researchers say it may be even more useful for prenatal diagnosis, detecting up to 200 genetic abnormalities, while returning ambiguous results in only 1% of cases.

Since prenatal genetic screening is most often an elective procedure, prospective parents can avoid the undue stress of a flood of prenatal genetic information, if they so choose. Many parents-to-be decide that results of prenatal genetic testing will not change or affect their decision to continue a pregnancy, so they opt out of it.

Neoglycoproteins and neoglycopeptides

Recent developments in glycobiology have shown the importance of glycoproteins and their derived glycopeptides in immunologicals processes, tissue differentiation, function of protein ligands and receptors, infectious agents and many other biological processes. Therefore, there is a need for a supply of these compounds to satisfy the needs of the researchers. Glycosylation, the process of adding carbohydrate residues to a polypeptide, is an enzymatic process that readily occurs at the asparagine, serine and/or threonine residues. Yet, glycosylation of these residues by synthetic methods is not easy to achieve.

It has become evident is that the nature of the link between the amino acid residue and the sugar as well as the nature of the amino acid itself is not crucial for the functions of the glycosylated product. What appears to be important is the nature of the oligosaccharide chain and in some cases its location in a polypeptide chain. Based on these findings a new kind of bioconjugates of carbohydrates linked to proteins or peptides has been developed, called neoglycoproteins or neoglycopeptides respectively. The amino acids of choice to substitute the asparagine, serine or threonine residues are lysine and cysteine. The reasons for selecting these amino acids being their available functional groups, amino and thiol correspondingly, which readily react with a number of well identified activated linkers. Other alternative sites in polypeptides available for glycosylation are the terminal amino and carboxyl groups. The possibility of selecting the size of the linker chain may allow the optimization of the conditions for recognition of the carbohydrate moieties by certain receptors.

For instance, studies concerning fertilization had shown that neoglycoproteins built using serum albumin as the required backbone can be used to identify the oligosaccharides responsible for initiating key events during this process. A similar approach using serum albumin as a scaffold for the oligosaccharides had been used to identify the cell receptors for some infectious agents, e.g. Porphyromonas gingivalis and Toxoplasma gondii. In general neoglycoproteins are largely used to identify or study the roles of the sugar moieties.

Recent advances in peptide synthesis can allow the preparation of authentic neoglycopeptides by using glycosylated amino acids as building blocks, thus avoiding the need to express the protein in a cell system. Applications of neoglycopeptides can be found in the targeting and translocation of oligonucleotides. The sugar moiety would be responsible for targeting specific cells, while the peptide would carry out the translocation of the oligonucleotides. Thus, neoglycopeptides offer new avenues for diverse areas of research. Bio-Synthesis has been producing synthetic peptides for over 25 years. Our expertise in custom synthetic polypeptide manufacturing allows us to produce the high-quality, large-scale, and GMP peptides with the highest success rate with long standing records. We have been delivered more than 100,000 peptides to customers worldwide, including very hydrophobic polypeptide, peptide with multiple disulfide bonds, multi-phosph0rylated peptides and extremely long peptides. Our large scale non-GMP ever delivered 5 kilograms of peptides on a single order and has the capacity of 10,000 peptides per month. Our capacity of GMP peptide is 10 kilograms.

How to determine the extinction coefficient of the PNAs in water at room temperature?

Normally, the extinction coefficient (e) could be calculated at wave length 260 nm, based on the # of base A, C, G, T in a PNA and their extinction coefficient respectively. The formula is:

e = [ 13.7 × # of A + 6.6 × # of C +11.7 × # of G + 8.6 × # of T ] mL/(µmole × cm)

If known the concentration (c) of a PNA solution, the extinction coefficient (e) could also be calculated by measuring its absorbance (A) at 260 nm. The calculation formula is:

e = A/(c × l)

note: l is the path length of the light travels through the solution

In order to get a good result, the value of absorbance (A) should be within 0.1 ~1.0 when do the measurement.