GENC 5142 Human Cytogenetics
Summer 2010 Midterm Examination

1. Which of the following four couples faces the greatest risk for live birth of an infant with unbalanced chromosome complement resulting in anomalies and mental retardation?

A. A couple in whom one of the persons is a balanced carrier for a large paracentric inversion. B. A couple in whom one of the persons is a balanced carrier for a large pericentric inversion. C. A couple in whom one of the persons is a balanced carrier for a small paracentric inversion. D. A couple in whom one of the persons is a balanced carrier for a small pericentric inversion.

2. Absence of recombination between a homologous pair of chromosomes during meiotic prophase I, or recombination between the homologous pair that is telomeric increases the likelihood of non-disjunction of that pair of chromosomes in Meiosis I. Given the data on Trisomy 18 pregnancies, which of the following is the leading hypothesis regarding generation of a Trisomy 18 conceptus?

E. Also absence of recombination between the homologous chromosome 18’s during meiotic prophase I F. A couple in whom one of the persons is a balanced carrier for a Robertsonian translocation G. Recombination between the homologous chromosome 18’s during meiotic prophase I that is telomeric, near the q arm telomeres H. Recombination between the homologous chromosome 18’s during meiotic prophase I that is pericentromeric, near the centromeres I. Barring a chromosome 18 rearrangement, advanced maternal age is the only contributing factor

Bruce - Trisomy 18 has been quoted to occur two times more likely as a result of Meiosis II errors than Meiosis I errors. This is much different than all the other trisomies as they occur more often in Meiosis I. A recent group though, showed by polar body FISH analysis contradictory results in that Trisomy 18 occurs as a result of Meiosis I errors. Most of our resources that we've used still quote that the generation of a trisomy 18 conceptus results from a Meiosis II error. It has also been seen that Meiosis II non-disjunction errors are not described by the entanglement model which predicts increased recombination, especially near the centromere. All this being said, my best guess for this question will be answer C and I hope we might be able to clarify this at some point.

3. Several syndromes show particular chromosome instability. Which of the following is characterized by premature centromere separation or heterochromatin repulsion?

J. Ataxia Telangiectasia K. Bloom Syndrome L. Fanconi Pancytopenia M. ICF Syndrome N. Robert Syndrome

4. Look at Karyotype 1. The only chromosome that is abnormal has an arrow pointing toward the abnormality. This is the result of an amniocentesis in which the woman’s only indication for prenatal diagnosis was Advanced Maternal Age. The amnio was performed at 16 weeks gestation and the amniotic fluid AFP measurement is within the normal range.

As the genetic counselor for the case, briefly write how you would work up the case. Also list the possible fetal interpretations of this amniocentesis result depending on what additional testing you recommend to the couple.

The first thing I would investigate for the family would be to do chromosomal studies on each of the parents. By obtaining a karyotype of each of the parents it may allow for the determination if one of the parents is a balanced translocation carrier. If it is determined that one of the parents is a balanced chromosomal carrier it may be seen that FISH studies would be beneficial to determine which part of which chromosomes are stuck together. If obtaining chromosomes from a parent is not likely to happen, FISH studies on the fetus may be a good practice to determine what part or parts are now on chromosome 8. This may lead to future literature investigation