L48: Chromosomal Aberrations Flashcards
Explain the meiotic problems arising from an inversion
- Inversion results when a c/s suffers two breaks and the broken off fragment is re-inserted in the wrong orientation. - As this is a type of balanced alteration, carriers are asymptomatic - Problems arise in offspring as chromosome with inverted region forms inversion loop during pairing with normal homolog. If crossing over occurs, material is translocated and some gametes are inviable.
Explain the rationale and procedure for karyotyping
- Karyotype: study of the chromosome composition - Rationale: problems of early growth/development, stillbirth/neonatal death, fertility problems, pregnancy with advanced maternal age, cancer, family history - Procedure: culture live cells from pt (most often lymphocytes), arrest cells in metaphase, lysing cells in hypotonic solution, fix spread chromosomes on microscope slides, stain (Giemsa stains AT rich bands and FISH)
Explain how the Philadelphia chromosome affect the health of a carrier
- Philadelphia chromosome = translocation bw c/s 9 & 22 - ABL tyrosine kinase is moved from 9 to BCR region on 22. - BCR-ABL protein functions as dominant oncogene causing CML
Name two main sources for mutations affecting chromosome structure
1.) Nonhomologous End Joining during double-strand break repair 2.) Unbalanced recombination between non-homologous sequences
Compare and contrast balanced and unbalanced alterations
- Balanced: does not change the amount of DNA in the affected cell and there is often no impact on the carrier - Unbalanced: reduces or increases the amount of DNA per cell, often impacting carrier severely
Describe chromosomal defects in cri-du-chat
- Deletion in chromosome 5 p. Usually a new mutation - Facial changes: microcephaly, hypertelorism (wide set eyes), micrognathia (undersized jaw). Brain/CNS changes: severe mental retardation. Cardiovascular: heart defects. Characteristic cat-like cry.
Describe chromosomal defects in Di George Syndrome
- Deletion in chromosome 22 q. Frequency = 1/4000. Usually a new mutation - Malformations include: congenital heart defect, immunodeficiency, hypoparathyroidism, mental retardation, cleft palate
Explain why balanced chromosomal alteration often cause infertility of otherwise health carriers. Explain the inheritance of balanced alterations.
- Carriers of balanced alterations ~ 0.2% of live births are not aware of their condition as there is typically no impact on the carrier - Their genetic abnormality does; however, shows at reproduction when they lead to the production of aberrant gametes. See image below
Describe the characteristics of a pedigree of a family with a chromosomal aberration
1.) Chromosomal aberrations cause multiple abnormalities usually with developmental delay. Presence of several individuals with multiple abnormalities in a pedigree points to chromosomal inheritance. 2.) Chromosomal aberrations frequently cause spontaneous abortions. Multiple miscarriages are a second indicator for chromosomal inheritance. 3.) Chromosomal aberrations frequently cause infertility.
Explain how to the Robertsonian translocations affect the health of a carrier
- Robertsonion translocation is movement of long and short arms of two chromosomes. Result = one chromosome composed of both the long arms the other composed of both of the short arms. The shorter derivative chromosome does not contain essential genetic information and is typically lost during cell division. Common Robertsonion translocation involves c/s 13 q and 14 q – happens at frequency of 1/1300.
Numerical chromosomal aberrations seen in humans
1.) Autosomes - Trisomy 13 – Patau - Trisomy 18 – Edward - Trisomy 21 – Down 2.) Sex Chromosomes - 45X: Turner - 47XXY: Klinefelter - 47XYY - 47XXX
Give the frequency of chromosomal aberrations, both at conception and at birth
- Structural chromosomal abnormalities (rearrangements, loss and duplications) occur in approximately 0.5 % of pregnancies and 0.2 % of live births
