An infant born to a 34-year-old woman has a flat facial profile, prominent epicanthal folds, and a holosystolic murmur heard loudest at the left sternal border. Karyotype analysis is consistent with trisomy 21. Maternal and paternal karyotypes are normal. A restriction fragment length polymorphism (RFLP) analysis is conducted to determine the parental origin of the extra chromosome. DNA samples from the child, mother, and father are obtained and the DNA is fragmented with a restriction enzyme. The fragments are then sorted by size using the Southern blot technique. Labeling is done using a probe that binds to a specific DNA sequence close to the centromere of chromosome 21. RFLP analysis for the child, mother, and father is shown below. In which of the following meiosis events did the nondisjunction most likely occur?

Question

An infant born to a 34-year-old woman has a flat facial profile, prominent epicanthal folds, and a holosystolic murmur heard loudest at the left sternal border.  Karyotype analysis is consistent with trisomy 21.  Maternal and paternal karyotypes are normal.  A restriction fragment length polymorphism (RFLP) analysis is conducted to determine the parental origin of the extra chromosome.  DNA samples from the child, mother, and father are obtained and the DNA is fragmented with a restriction enzyme.  The fragments are then sorted by size using the Southern blot technique.  Labeling is done using a probe that binds to a specific DNA sequence close to the centromere of chromosome 21.  RFLP analysis for the child, mother, and father is shown below.  In which of the following meiosis events did the nondisjunction most likely occur?

Quizplus · Accepted Answer

11ec160b_3760_bac0_9249_695b1e3c283d_MD0001_00 Nondisjunction is the failure of chromosome pairs to separate properly during cell division. This could be due to a failure of homologous chromosomes to separate in meiosis I or a failure of sister chromatids to separate during meiosis II or mitosis. In monosomy, a single chromosome is lost. In trisomy, a single chromosome is gained. Monosomies or trisomies can result from nondisjunction in meiosis I or II. Restriction fragment length polymorphism (RFLP) analysis shows that both parents demonstrate 2 bands. Each parental band represents a homologous chromosome 21. The child has 3 bands, indicating that he has 3 different versions of chromosome 21 that he obtained from his parents. He received the lower band from the father and both of the upper bands from the mother. The fact that he received 2 different bands from the mother indicates that he inherited both of her homologous chromosomes. Therefore, the problem occurred in the mother during meiosis I, when homologous chromosomes are separated. In fact, the vast majority of Down syndrome cases arise due to nondisjunction during maternal meiosis I. (Choice B) If the mother had a failure in meiosis II, the child's RFLP analysis would reveal only two bands (see example). There would be a single band from the father and a darker, thicker band from the mother. The darker, thicker band signifies the inheritance of both sister chromatids, which will produce equal-size restriction fragments (but twice the normal amount). (Choice C) If the father had a failure in meiosis I, the child's RFLP analysis would reveal 3 bands (see example). In this instance, there would be a single band inherited from the mother with two bands inherited from the father. (Choice D) If the father had a failure in meiosis II, the child's RFLP analysis would reveal two bands (see example). In this instance, there would be a single band inherited from the mother and a second band from the father. The father's band would be darker and thicker, signifying the inheritance of both sister chromatids. Educational objective: Nondisjunction is the failure of chromosome pairs to separate properly during cell division. This could be due to a failure of homologous chromosomes to separate in meiosis I or a failure of sister chromatids to separate during meiosis II or mitosis. __________ References: The meiotic stage of nondisjunction in trisomy 21: determination by using DNA polymorphisms. (http://www.ncbi.nlm.nih.gov/pubmed/1347192)

An Infant Born to a 34-Year-Old Woman Has a Flat