24-Chromosome Screening with Translocation and Inversion Diagnosis

Pre-Implantation Genetic Diagnosis (PGD) allows for the diagnosis of inherited diseases or conditions within an embryo during In Vitro Fertilisation (IVF). In the case of PGD for a Translocation and/or Inversion, embryos are tested for an unbalanced chromosomal rearrangement called an unbalanced translocation or inversion due to a balanced chromosomal rearrangement in one of the parents. With locations in the United Arab Emirates (Dubai and Abu Dhabi), Australia, the Kingdom of Saudi Arabia, Lebanon and more locations coming soon, Viafet's services are available to a wide network of clinicians and patients

Viafet's ExactCCSPLUS™ is an important tool for couples who are carriers of balanced chromosomal rearrangements to simultaneously screen all 24 chromosomes (1-22, X and Y) for aneuploidy and unbalanced translocations or inversions that may occur in embryos due to their specific balanced chromosomal rearrangement. Couples with balanced chromosomal rearrangements undergoing IVF with genetic screening such as ExactCCSPLUS™ are at a significantly decreased risk of miscarriage and chromosomally abnormal live births.

If requested, ExactCCSPLUS™ can also diagnose instances of haploidy , polyploidy and uniparental disomy in embryos -- this requires blood samples from the couple at the start of an IVF cycle. With over 15 years of experience in Reproductive Genetics, during which over 15,000 samples have been tested, Viafet specialises in PGD and PGS.

Is ExactCCSPLUS™ right for me?

Couples with the following medical histories most often select to complete ExactCCSPLUS™ with their IVF cycles:


Balanced Chromosomal Rearrangements

In about 5% of couples with more than one miscarriage, one person is found to have a balanced chromosomal rearrangement. Carriers of balanced chromosomal rearrangements are usually perfectly healthy and unaware that they have a balanced chromosomal rearrangement. However, more than 70% of pregnancies in couples where at least one parent carries a balanced chromosomal rearrangement will result in miscarriage while up to 10% may result in a chromosomally abnormal live birth. This is due to a resulting unbalanced chromosomal rearrangement developing in the embryos. Balanced chromosomal rearrangements can easily be identified in the couple through a simple test called karyotyping completed through blood test. To learn more about completing karyotyping, consult with your physician.

A balanced chromosomal rearrangement is when all of the genetic information is present in the correct amount but it is in the wrong location or in a different order. Chromosomal rearrangements may occur during egg, sperm or embryo development. Balanced chromosomal rearrangements exist as either translocations or inversions .

  • Balanced Translocation: Balanced translocations occur when two or more pieces break off from two or more different chromosomes and swap places. One particular kind of balanced translocation is known as a Robertsonian Translocation.
  • Balanced Inversion: In a balanced inversion, a chromosome breaks in two places and the resulting piece of DNA is reversed and re-inserted into the chromosome.

In both balanced translocations and inversions, chromosomal material is equally rearranged so that the same amount of genetic material is present but it has moved to a different place. Individuals with balanced chromosomal rearrangements are perfectly healthy, although they may face difficulty in conceiving and are more likely to have children with unbalanced chromosomal rearrangements. If either parent carries a balanced translocation or inversion, it is possible for their child to inherit a balanced or unbalanced chromosomal rearrangement. If they inherit a balanced chromosomal rearrangement, similar to their parents, they will be perfectly healthy. However, a child with an unbalanced chromosomal rearrangement either has additional or missing chromosomal material that can lead to a chromosomal disorder. The severity on the disorder depends on the chromosomes involved and the amount of missing or additional genetic material.

Based on your medical history, Viafet advises you to consult with your physician in order to determine if completing genetic testing such as ExactCCSPLUS™ is right for you. For more information on ExactCCSPLUS™, to discuss any questions related to genetic testing, or to learn where you may complete an IVF cycle with ExactCCSPLUS™, contact Viafet today. Our team of geneticists is available by phone or email to answer any questions you may have.


Robertsonian Translocation

A Robertsonian translocation is a rare form of chromosomal rearrangement that occurs in five chromosomes pairs known as acrocentric, namely chromosomes 13, 14, 15, 21 and 22. Acrocentric chromosomes differ from other chromosomes in that they possess a centromere that partitions the chromosome into a long arm, containing the majority of genetic material, and a short arm, containing a much smaller portion of genetic material. A Robertsonian translocation may involve two homologous (paired) chromosomes or non-homologous chromosomes (two different chromosomes, not belonging to a pair).

During a Robertsonian translocation, the participating chromosomes break at their centromeres and the long arms fuse together to form a single chromosome with a single centromere. The short arms also fuse together, which typically amount to a chromosome with nonessential genes that is usually lost within a few cell divisions.

Most people with Robertsonian translocations have 45 (rather than 46) chromosomes in each cell, however all essential genetic material is present and they appear normal. However, their children may either be normal or carry the fusion chromosome, or they may inherit a missing or extra long arm of an acrocentric chromosome. Completing screening during your IVF cycle will enable you to identify any embryos carrying a Robertsonian translocation. If you have any questions or would like to discuss your personal medical history with a geneticist, contact Viafet today.



Uniparental Disomy

Uniparental disomy (UPD) occurs when an individual receives two copies of a chromosome, or of part of a chromosome, from one parent and no copies from the other parent.

In rare instances, UPD can occur in a chromosome carrying a recessive disorder, resulting in rare recessive disorders. UPD should be suspected if they are affected by a recessive disorder of which only one parent is a carrier.

If a UPD occurs in a chromosome carrying imprinted genes it can result in physical disabilities. Though few imprinted genes have been identified, UPD of an imprinted gene can result in the loss of gene function - this can lead to delayed development, mental retardation or other medical problems.

In cases where UPD occurs in a chromosome that is not carrying a recessive disorders or one that is not involved in imprinting, the individual is most likely unaffected.

Examples of diseases associated with UPD include Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome.


Haploidy

Haploidy occurs when an embryo has only one set of chromosomes in each pair, amounting to a total of 23 chromosomes rather than 46. Haploid embryos do not survive during pregnancy and will result in abortion or no pregnancy.


Polyploidy

Polyploidy refers to a numerical change in the entire set of chromosomes. Instead of having 46 chromosomes, polyploid embryos will have 69 chromosomes (refers to as triploidy) or 92 chromosomes (tetraploidy). The extra set of chromosomes observed in triploid embryos may be the result of either mother or father. Tetraploidy is more rarely diagnosed than triploidy, though both instances are quite rare.

How does ExactCCSPLUS™ work?

When?

Completing genetic testing during your IVF cycle provides a wealth of information about each embryo before being transferred back to your uterus. During an IVF cycle, PGD for unbalanced translocations or inversions with simultaneous 24-chromosome aneuploidy screening can be performed day 3, 4 or 5 after Egg Retrieval. A single cell or cells are removed from the developing embryo and sent to Viafet for testing. Results are available 24-hours after receiving the samples. Viafet's fast reporting time allows for embryos to be transferred fresh or frozen, depending on your IVF physician's protocol.

How?

ExactCCSPLUS™ is performed by array-CGH, a method that amplifies (magnifies) and compares the amount of DNA present for all 24 chromosomes (1-22, X and Y) to that of a healthy standard, detecting monosomies (missing chromosomes), trisomies (extra chromosomes) and other abnormalities. In 2004, the founder of Viafet Genomics Laboratory, Dr. Ali Hellani, established a new method of DNA amplification that improved the quantity and quality of resultant DNA from one embryonic cell. Today, after being adopted as the array-CGH protocol of Agilent Technologies, Dr. Hellani's protocol is utilized by scientists worldwide completing PGS through array-CGH.

In comparison to ExactCCS™ which screens all embryos for aneuploidy, ExactCCSPLUS™ testing produces a result with higher resolution that allows for inversions or translocations of small size to be detected.

If haploidy , polyploidy or uniparental disomy testing is requested with ExactCCSPLUS™ a second method will be utilized that can detect variations in the DNA called SNPs. Through this method, Viafet is able to report if a chromosome is inherited from the mother or father.

Results obtained through this method are >99% accurate.

Where can I get testing?

Talk to your IVF physician about PGD and if it right for you. If your physician does not yet offer Viafet testing, please suggest that they contact us - testing can get started immediately. If your physician is already offering Viafet testing, all coordination for your case will be completed between your IVF centre and Viafet's team.

With locations in the United Arab Emirates (Dubai and Abu Dhabi), Australia, the Kingdom of Saudi Arabia, Lebanon and more locations coming soon, Viafet's services are available to a wide network of clinicians and patients. If at any time during your journey you have questions or would like to speak with a Genetic Counselor, contact Viafet and we will schedule an appointment immediately.