* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Unbalanced Translocation Breakout
Hybrid (biology) wikipedia , lookup
Human genetic variation wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Saethre–Chotzen syndrome wikipedia , lookup
Fetal origins hypothesis wikipedia , lookup
Gene expression programming wikipedia , lookup
Public health genomics wikipedia , lookup
Medical genetics wikipedia , lookup
Genetic engineering wikipedia , lookup
Cell-free fetal DNA wikipedia , lookup
Preimplantation genetic diagnosis wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
DNA paternity testing wikipedia , lookup
Designer baby wikipedia , lookup
Genetic testing wikipedia , lookup
Microevolution wikipedia , lookup
Y chromosome wikipedia , lookup
X-inactivation wikipedia , lookup
Genome (book) wikipedia , lookup
Unbalanced Translocation Breakout Kent Nicholls 5p- Society Rebecca Okashah Genetic Counselor Children's Hospital of San Antonio July 26, 2014 San Antonio, TX 5p- Society Annual Conference Revised 8/3/2014 Balanced & Unbalanced Translocations Defined • Balanced Translocation • A chromosome abnormality caused by pieces of separate chromosomes breaking off of their original chromosomes and switching places. All of the genetic material is present (balanced). • Unbalanced Translocation • When an unbalanced translocation occurs, there is both too much of one chromosome and too little of another chromosome present as a result of pieces of separate chromosomes breaking off of their original chromosomes and switching places. • In 5p-, the translocation involves the short arm (p) of chromosome 5 and any chromosome. What causes an unbalanced translocation? • One parent has a balanced translocation • New occurrence at conception (meiosis) Diagram of a translocation (reciprocal) Possible Results • For example, if there is a parent with a balanced translocation involving 5p and 10q having a child, the possible results are: a) Normal b) Translocation carrier – child has a balanced translocation c) 5p- and 10q+ Partial monosomy of some portion of 5p and trisomy of some portion of 10q. d) 5p+ and 10qTrisomy of some portion of 5p and partial monosomy of some portion of 10q. • Mathematical risk is 25% for each possibility, but in practice, the expected risk of carrying a child to term with an unbalanced translocation (either c or d above) is approximately 20% How is an unbalanced translocation detected? • An unbalanced translocation is usually detected by a blood test at birth or by an amniocentesis or CVS during pregnancy. Recurrence Risk for Future Children • If a child has an unbalanced translocation and the parents do not have a balanced translocation, then the risk for future children is approximately 1%. • If a child has an unbalanced translocation and one of the parents has a balanced translocation, then the risk for future children is approximately 20%. • 70% of translocations are inherited • the balanced translocation is equally likely to be from the mother or the father • the risk of a future child having an unbalanced translocation is also affected by the size of the balanced translocation. A person with an unbalanced translocation is unique • 5p- unbalanced translocations occur in about 10% of 5pcases • Missing genetic material (5p deletion) and added genetic material (partial duplication of another chromosome). • The amount of protein synthesized is often proportional to the number of gene copies present • Extra genes can lead to excess protein and deletions can also affect gene dosage • Each child is unique with virtually infinite combinations of missing and added material. • 5p- is a spectrum disorder • Classically defined Cri du Chat syndrome does not accurately encompass the symptoms experienced by these children. Prognosis for this group of children • Our families are writing the book on this! • Anecdotal observations suggest those persons with a 5p- unbalanced translocation may perform toward the low end of the range of the 5p- spectrum. • Insufficient information is available for persons with a 5p+ unbalanced translocation. Options for having more children • This is a very personal family decision and we respect that! • Adoption • Prenatal Testing • Chorionic villus sampling (CVS) – at about 11 to 12 weeks • Amniocentesis – at about 16 to 18 weeks of pregnancy • Non-Invasive Prenatal Testing (NIPT) analyzes cellfree fetal DNA circulating in maternal blood – at about 10 to 22 weeks In Vitro Fertilization (IVF) • Analyze, select and transfer only embryos that do not have abnormalities in their chromosomes • Comprehensive Chromosome Screening (CCS) • Obtain 5-10 cells on day 5 or 6 from blastocyst • Examine cells with quantitative real-time polymerase chain reaction (qPCR) • Preimplantation Genetic Diagnosis (PGD) of embryos prior to transferring to the uterus • A single blastomere is removed on day 3 • Genetic evaluation is performed using PCR, FISH, or comparative genomic hybridization (CGH). • Process, limitations, issues, successes Personal Stories • SB – personal experience with IVF • LD – personal experience with IVF • Other stories from break-out attendees Research Suggestions • What can be done to mitigate symptoms and enhance quality of life? Q&A with Rebecca Okashah • Can an unbalanced translocation be missed on test and leave other family member at risk? • Can an unbalanced translocation be mosaic? • Why is my child not similar to another child with the same chromosome unbalanced translocation (i.e. 5 & 10) • Are some unbalanced translocations less impactful, such as 5 & x? • What is about 5p+ children? • What if our family has multiple people with 5p- but no translocation is identified? Internet links for more information • Comprehensive Chromosome Screening (CCS) • • • • http://www.medscape.com/viewarticle/817499 http://www.rmact.com/getting-started/fertility-testing/ccs-comprehensivechromosome-screening http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0061838 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348286/ • Preimplantation Genetic Diagnosis (PGD) • • • http://emedicine.medscape.com/article/273415-overview http://www.givf.com/geneticservices/whatispgd.shtml#chromosomerearrangemen t http://www.pennmedicine.org/fertility/patient/clinical-services/pgdpreimplantation-genetic-diagnosis/ • Non-Invasive Prenatal Testing (NIPT) • • http://www.rcog.org.uk/files/rcog-corp/SIP_15_04032014.pdf http://www.ncbi.nlm.nih.gov/pubmed/24785862