Cytogenetics
Core concepts
Master the karyotype nomenclature (ISCN): p and q arms, band numbering, and the meaning of common designations such as 46,XX, 47,+21, 45,X, 46,XY,t(9;22)(q34;q11.2), del(5p), inv, dup, and ish/arr prefixes. Understand resolution limits, the difference between balanced and unbalanced rearrangements, mosaicism (and how it is expressed as a ratio in ISCN), and Robertsonian vs reciprocal translocations.
Know the roles of G-banding, FISH, CMA, and optical genome mapping. Understand meiotic segregation patterns in carriers of balanced translocations (adjacent-1, adjacent-2, alternate, 3:1) and the resulting risk of unbalanced offspring. Recognize common microdeletion syndromes (22q11.2, 15q11-q13, 7q11.23, 16p11.2) and their detection method.
Traps
Questions often confuse balanced vs unbalanced - a balanced translocation carrier is typically phenotypically normal but at reproductive risk. Another trap: assuming a normal karyotype excludes a microdeletion (it does not). Watch for mosaic vs non-mosaic reporting, and for confusing a Robertsonian translocation (whole-arm fusion of acrocentrics 13,14,15,21,22) with a reciprocal one. Remember that CMA does not detect balanced rearrangements.
Rule of thumb
Balanced = phenotype usually normal, reproductive risk; unbalanced = phenotype affected, dosage change. If the question asks about recurrence risk in a translocation carrier, think segregation patterns, not variant classification.
Worked example
A couple with recurrent pregnancy loss: maternal karyotype shows 46,XX,t(11;22)(q23;q11.2). This is a balanced reciprocal translocation; offspring may inherit unbalanced derivatives, so prenatal diagnosis with karyotype or CMA (plus karyotype for balance) is offered.