5- Cytogenetics - mine

Microdeletions and duplications mediated by segmental duplications are recurrent due to their underlying mechanism. Which of the following disorders is the most common recurrent microdeletion syndrome? A. Aniridia-Wilms tumor B. Retinoblastoma C. Prader-Willi syndrome D. VCF/DiGeorge syndrome E. Cri-du-chat syndrome

22q11 deletion syndrome--including DiGeorge syndrome and VCF (velocardiofacial syndrome) is the most common deletion syndrome in humans, occurring in ~1/4000 births. This is a common, recurrent microdeletion mediated by NAHR of flanking low-copy repeats (LCRs). Other LCR genomic disorders (PWS, AS, Williams, Smith-Magenis, Sotos) occur at ~1/10,000- 1/20,000. Random deletion syndromes such as cri du chat, Wolf-Hirschhorn, Miller-Dieker syndrome, retinoblastoma, aniridia-Wilms tumor are less common (1/50,000-1/100,000 or less). The correct answer is D.

A balanced reciprocal translocation is observed in cells from an amniotic fluid sample. What should your next step be? A. Chromosome analysis on the parents to see if one has the same translocation B. High resolution banding to better determine the chromosome breakpoints C. Microarray studies to determine which genes are affected by the rearrangement D. No additional studies since the translocation appears balanced. E. Prenatal screening test for alpha-fetoprotein and human chorionic gonadotrophin

A

A couple has a child with Down syndrome who has a karyotype of 47,XY,+21. The probability for their next child to have Down syndrome is closest to: A. 1% B. 5% C. 10% D. 15% E. 33.30%

A

A patient has mosaic Down syndrome. Which one of the following is least likely to result in this phenotype? A. Dispermy B. Fusion of a zygote with a karyotype of 46,XX with another zygote with a karyotype of 47,XX,+21 C. Fusion of a zygote with a karyotype of 46,XX with another zygote with a karyotype of of 46,XX,-21,=rob(21q21q) D. Meiotic non-disjunction with anaphase rescue during mitosis after fertilization E. Mitotic non-disjunction after fertilization

A

A patient with the karyotype 46,XX,t(1;5) has A. A balanced translocation between chromosomes 1 and 5 B. An unbalanced translocation between chromosomes 1 and 5 C. A chromosomal aneuploidy D. A ring chromosome E. A Robertsonian translocation

A

About 90% of trisomy 21 Down conceptions are due to nondisjunction during a) meiosis I in the female. b) meiosis II in the female. c) meiosis I in the male. d) meiosis II in the male.

A

Comparative genomic hybridization (CGH) is one method that can be used for copy number variation (CNV) detection. Which of the following issues is a limitation of this methodology compared to a G-banded karyotype? A. Cannot detect polyploidies B. Cannot detect single copy differences C. Cannot detect unbalanced translocations D. Lower resolution than G-banded karyotype E. Requires cells to be cultured

A

During your time in the Genetics clinic you are asked to call the cytogenetics lab for results of a peripheral blood analysis for a healthy 34-year old man with a history of infertility. The lab faxes over the report which reads: 46,XY,t(9;22)(p22;q13) What is the most likely interpretation of these results? A. He has a balanced translocation between 9p and 22q B. He has an unbalanced translocation between 9p and 22q C. He has the Philadelphia translocation and should see an oncologist immediately D. He has a balanced translocation between 9q and 22q E. He has an unbalanced translocation between 9q and 22q

A

FISH testing is not used in routine diagnosis of cystic fibrosis (CF). The reason is that A. FISH is better for detecting large deletions and most CF mutations are point mutations or small deletions B. FISH is better for detecting point mutations and most CF mutations are large deletions C. FISH is better for detecting translocations and most CF mutations are not caused by translocation D. FISH is not appropriate for detecting homozygous mutations E. Other genes related to the CF gene may make the background too high for FISH

A

In a (an)____, the short arm of two acrocentric chromosomes break, and the long arms join, forming an unusual, long chromosome. a) Robertsonian translocation b) reciprocal translocation c) inversion d) duplication

A

In a cytogenetics laboratory, the prometaphase preparation differs from the metaphase preparation in that in the prometaphase preparation: A. The chromosomes appear longer and banding resolution is higher B. The chromosomes appear longer and the banding resolution is lower C. The chromosomes appear shorter and the banding resolution is higher D. The chromosomes appear shorter and the banding resolution is lower E. the chromosomes are the same length as is the banding resolution

A

Microarray-based comparative genomic hybridization studies are well suited for the detection of all of the following except: A. Balanced chromosomal translocations B. Deletion C. Duplication D. Monosomy E. Trisomy

A

Mosaicism differs from chimerism in which one of the following ways? A. Mosaics are derived from one zygote while chimeras arise from the fusion of two (or more) different zygotes or embryonic stem cells B. Chimeras are genetically identical from cell to cell, except for one locus, while mosaics differ at multiple alleles at many loci C. All females (with a randomly inactivated X chromosome in every nucleated cell) are mosaic while all males (X chromosome from their mother and Y chromosomE from their father) are chimeras D. Mosaics have heterogeneous germ cells only while chimeras have heterogeneous somatic cells only E. While one can be mosaic to varying degrees one cannot be chimeric to varying degrees

A

The short arms of chromosomes 13, 14, 15, 21 and 22 contain multiple copies of ribosomal RNA genes. Deletion of one or more of these short arms is generally inconsequential. Because of the almost negligible length of the short arms, these chromosomes are called A. acrocentric chromosomes B. isochromosomes C. metacentric chromosomes D. ring chromosomes E. submetacentric chromosomes

A

The technique in which equal amounts of patient DNA and control DNA is used to compete for binding to a large number of DNA templates is called A. comparative genomic hybridization B. DNA library screening C. in situ hybridization D. real-time polymerase chain reaction E. Southern hybridization

A

Using a probe that detects the telomeres of all chromosomes during interphase in a fluorescence in situ hybridization study, you observed 90 dots of light per cell nucleus. Which one of the following karyotypes is most compatible with the study results? A. 45, -21,-22,+t(21;22) B. 46, XY C. 46, XY,-7,+der(7)t(7;15) D. 46, XY,-22,+t(21;22) E. 46, XY,t(7;15)

A

Which of the following individuals has the LOWEST risk of generating abnormal offspring? A. A carrier of a paracentric inversion B. A carrier of a Robertsonian translocation C. A carrier of a balanced reciprocal translocation D. A carrier of a pericentric inversion

A

Which one of the following DNA elements ensures correct segregation of homologous chromosomes during meiosis and mitosis? A. Centromeres B. Nucleosomes C. Origins of replication D. Satellites E. Telomeres

A

Which one of the following cytogenetic abnormalities found in a first trimester fetus results in the highest rate of spontaneous fetal loss? A. 45,X B. 47,XX,+18 C. 47,XX,+21 D. 47,XXX E. 47,XXY

A

Which one of the following cytogenetic abnormalities is expected to yield abnormal results when fluorescence in situ hybridization (FISH) using probes for the sub-telomeric regions of all 24 chromosomes (22 autosomes, X and Y) is performed? (Note: all probes are labeled with the same fluorochrome) A. 45,X/47,XXX B. 46,XY,t(4;8)(p22;q32) C. 46,XY,del(15)(q11-q12) D. 46,XY,dup(15)(q11-q12) E. 46,XY,inv(9)(q21q31)

A

Your fellow medical student confided in you that she has not attained menarche yet, and became worried after an endocrinology lecture that the class attended recently. Her past medical history is unremarkable except for an inguinal hernia repair in infancy. Family history was unremarkable, except for an aunt who could not bear children. She also revealed that her primary care physician was puzzled at her recent school physical that she had no pubic hair, but has fully developed breasts. You suspect a genetic cause for her primary amenorrhea. What is the most likely result of her chromosome analysis? a. 46,XY b. 45,X c. 46,XY/46,XX d. 47,XYY e. 45,X/46,XX

A

Your patient is a 4-year old boy with developmental delay. You order a whole genome comparative hybridization array (array CGH), and it comes back normal. Which of the following underlying explanations for developmental delay would this test be least likely to detect? a. Fragile X syndrome b. Down syndrome c. 22q11 deletion syndrome d. A de novo 1 Mb deletion on chromosome 15q e. A subtelomere rearrangement

A

Nondisjunction of chromosome 21 during meiosis II in human females can result in all of the following chromosome complements in a zygote except (assume the oocyte is fertilized by a sperm with a normal chromosome set) a) no chromosome 21. b) euploid for chromosome 21. c) monosomic for chromosome 21. d) trisomic for chromosome 21.

A. Nondisjunction of chromosome 21 during meiosis II in human females cannot result in no chromosome 21 in the zygote

A young woman is found to have a balanced translocation after a family history and pedigree analysis, during a preconception counseling visit, raised a red flag for a chromosomal abnormality. Based on this clinical finding, which of the following statements about chromosomal segregation and possible offspring is the most likely clinical outcome? A. Offspring resulting from alternate segregation will be chromosomally normal. B. Offspring resulting from alternate segregation are likely to be phenotypically normal. C. Offspring resulting from adjacent-1 segregation will be chromosomally normal. D. Offspring resulting from adjacent-1 segregation are likely to be phenotypically normal. E. Offspring resulting from adjacent-2 segregation are likely to be phenotypically normal.

Alternate segregation results in normal gametes and in gametes with balanced chromosomal translocation. Thus the offspring are phenotypically normal but not chromosomally normal in all cases. Offspring from adjacent-1 or adjacent-2 segregation will all be unbalanced and all will be chromosomally abnormal. They would also be phenotypically abnormal, except in very unusual circumstances. Adjacent segregation-1 is when homologous centromeres segregate, in contrast to adjacent-2 where the homologous centrmorees go to the same cell. Adjacent-2 is rare compared to adjacent-1. The correct answer is B.

A couple (both chromosomally normal) has a child with trisomy 21. Assuming the Down syndrome was caused by nondisjunction in maternal meiosis I, use the genotypes given to predict the mother's genotype. Genotypes for a chromosome 21 marker with two possible alleles: Father: [2,2] Down syndrome child: [1,2,2] Based on the information given, the mother's genotype is: A. 1,1 B. 1,2 C. 2,2 D. Uninformative; cannot be predicted

B

A man, Donald, with X-linked hemophilia, and a healthy woman, Shirley, whose father had X-linked hemophilia, have a healthy son, Kiefer, with Klinefelter syndrome (47, XXY). The son undergoes testing and is shown not to be a carrier of hemophilia. When was non-disjunction most likely to occur? A. maternal meiosis I B. maternal meiosis II C. paternal meiosis I D. paternal meiosis II E. Cannot tell from the information provided

B

An 18-year-old woman presents with primary amenorrhea and short stature. Physical exam reveals neck webbing, a low posterior hairline, a broad chest with widely spaced nipples. Which of the following is the most appropriate method for confirming her genetic disorder? A. Biochemical Testing B. Cytogenetic analysis C. Linkage analysis D. DNA methylation analysis E. PCR multiplex deletion test

B

An individual with the chromosomal description 45, X would be a: a) normal female. b) female with Turner syndrome. c) male with Klinefelter syndrome. d) cannot be determined.

B

Array CGH (array comparative genomic hybridization) is a microarray based technology that can be used alone or in addition to more traditional cytogenetic testing. Of the following options, which abnormality is most likely to be detected by array CGH? A.Balanced rearrangements including pericentric and paracentric inversions B.Small terminal deletions and duplications C.Partial loss of acrocentric short arm material D.Most Robertsonian translocations (except those involving homologous chromosomes) E.All categories of inherited (familial) chromosome rearrangements

B

Exchange of genetic material (crossing-over) between homologous chromosomes occurs during which phase and which division of meiosis? A. Interphase B. Prophase I C. Prophase II D. Metaphase I E. Metaphase II

B

In G-banding, the non-centromeric dark bands represent: A. α-satellite repeats B. AT-rich regions of chromatin C. euchromatin D. GC-rich regions of chromatin E. gene-rich regions of the chromosome

B

In nondisjunction, which parent leads to the sex chromosome aneuploid XYY? a) mother b) father c) either parent d) both parents

B

Klinefelter syndrome (47,XXY) is most often caused by meiotic nondisjunction. Of the following options, which error can be EXCLUDED as a potential cause of this chromosome abnormality? A.Male meiosis I nondisjunction B.Male meiosis II nondisjunction C.Female meiosis I nondisjunction D.Female meiosis II nondisjunction

B

Microdeletion syndromes are relatively rare, yet are a clinically important class of genetic disorders. Of the following statements, which provides the most likely etiology giving rise to microdeletions? A. Nondisjunction is more likely in older mothers. B. Low-copy repeats increase the chance of unequal crossovers. C. Linkage disequilibrium gives rise to haplotype blocks. D. Homologous chromosomes should segregate during meiosis I. E. SNPs are abundant and located throughout the genome.

B

Telomerase contains A. a single-stranded DNA template for elongation of the 3' overhang at the end of a chromosome. B. a single-stranded RNA template for elongation of the 3' overhang at the end of a chromosome. C. a single-stranded DNA template that makes Okazaki fragments for lagging strand synthesis unnecessary during telomeric extension. D. a single-stranded RNA template that makes Okazaki fragments for lagging strand synthesis unnecessary during telomeric extension. E. no nucleic acid component.

B

The photographic arrangement of chromosomes is called a (an) a) karyotype. b) idiogram. c) anagram. d) chromogram.

B

When you study the chromosomes of a patient using a fluorescence in situ hybridization (FISH) probe that detects all centromeres, you detect 46 dots of light. However, when instead you use a FISH probe that detects a gene of the long arm of the X chromosome, you see 3 dots of light. Which one of the following karyotypes is consistent with these findings? A. 45,X B. 46,X,i(Xq) C. 46,XX/47,XXX D. 47,XXX E. 47,XXY

B

Which one of the following represents an unbalanced translocation? A. 45, XY,-15,-22, +rob(15q;22q) B. 46, XY,-8,+der(8)t(8;20)(p12;q13) C. 46, XY,t(8;20)(p12;q13) D. 47, XXX E. 69, XXX

B

You see a 4-year-old in clinic with delayed milestones, cleft palate, history of a ventricular septal defect (VSD) repair, and lack of a thymus. The most appropriate genetic test to order is: A. Chromosome analysis to look for an extra chromosome B. FISH analysis to look for a deletion C. Whole genome sequencing as the specific mutation is not known D. Microarray testing to assess for a gene duplication

B

____ contains protein-encoding genes. a) heterochromatin b) euchromatin c) pericentric inversions d) aneuploids

B

Structural chromosome abnormalities result from an assortment of molecular mechanisms. Our knowledge is most complete for which of the following specific molecular mechanisms? A. terminal deletion B. interstitial deletion C. isochromosome D. reciprocal translocation E. ring chromosome

B is correct. Common, recurrent micodeletions (22q11, 17p11, 15q11-q13, etc.) are interstitial deletions with flanking low-copy repeats (LCRs) with very high sequence homology. In meiosis, mispairing of proximal and distal copies (non-allelic homologous recombination, NAHR), leads to unequal cross-over producing deletion or duplication. Specific mechanisms at a sequence level are not known for other classes of structural chromosome rearrangements. The correct answer is B

Chorionic villus sampling is performed on a 38-year-old woman who is concerned about having a child with a chromosomal disorder. Which one of the following karyotypes carries the highest risk for this woman to deliver a chromosomally abnormal livebom? A. 45,XX,der(13;14)(q10;q10) B. 45,XY,der (14;21)(q10;q10) C. 46,XY,inv(2)(p11.2q13) D. 46,XX,inv(2)(q31q35) E. 46,XX,t(11;22)(q23;q11.2)

Both maternal and paternal carriers of rob(13q14q) have about a 1% chance of having a child with translocation trisomy 13. Fathers who carry rob(14q21q) have less than a 1% chance of having a child with translocation Down syndrome. Both types of inversions, regardless of the parental origin, have almost no chance of abnormal offspring. The pericentric inversion (C) is a common inversion found in the population and the paracentric inversion (D) would result in nonviable dicentric and acentric products. Mothers who carry the t(11;22) are at a 6% risk for an abnormal offspring typically have 47 chromosomes with a small extra der(22) and have mental retardation and other anomalies. The correct answer is E.

A (an)____ chromosome has its centromere near a tip so that it has one long arm and one very short arm. a) metacentric b) submetacentric c) acrocentric d) none of the above

C

A 12 week fetus is noted to have a significantly increased nuchal translucency on ultrasound scanning. CVS is performed. What is the most likely karyotype finding? A. 47,XX,+13 B. 47,XX,+18 C. 47,XX,+21 D. 47,XXX

C

A 15-year-old boy is evaluated by a clinician for failure to develop normal male secondary sexual characteristics. Physical examination reveals small testes, a small penis, and gynecomastia. The boy has had some difficulties in school, but cognitive development is within normal limits. The child's condition is most likely due to which of the following? A. Deletion B. Nondisjunction of an autosome C. Nondisjunction of a sex chromosome D. Reciprocal translocation E. Robertsonian translocation

C

A 3-year-old female presents with short stature and her chromosome study shows a 45,X/46,X,+mar mosaic karyotype with a small marker chromosome of unknown origin. What is your major concern for this child? A. delayed onset of puberty B. developmental delays C. increased risk for gonadoblastoma D. increased risk for leukemia E. stigmatization due to stature

C

A man is found to have 45 chromosomes because his two chromosome 21s are joined at the centromere to form a single chromosome (i.e. 21/21 Robertsonian translocation). Which statement is true about his gametes? A. He has 23 chromosomes in each of his sperm. B. He has 22 chromosomes in each of his sperm. C. He has a mixture of sperms, some of which have 22 chromosomes and some have 23 chromosomes. D. He has 45 chromosomes in each of his sperm

C

A triploid human karyotype has how many chromosomes? a) 23. b) 46. c) 69. d) 92.

C

A two year old boy exhibits cognitive impairment, low set ears, Brushfield spots (speckled iris), a depressed nasal bridge and epicanthic folds. He is diagnosed with Down syndrome based on the results of a karyotype analysis. Which of the following events was the most likely cause of his condition? A. Fertilization of an ovum by two sperm B. Genomic imprinting C. Nondisjunction during meiosis D. Mitotic loss E. Reciprocal translocation

C

Alagille syndrome results from a (an) a) inversion. b) duplication. c) translocation. d) isochromosome

C

An individual with two normal sets of autosomes and a single X chromosome has a) Down syndrome. b) Patau syndrome. c) Turner syndrome. d) Klinefelter syndrome.

C

Approximately ____ percentage of spontaneous abortions result from extra or missing chromosomes. a) 10 b) 25 c) 50 d) 75

C

Consider the following normal sequence of genes: a b c d e f g h. The sequence a b f e d c g h represents a (an) a) deletion. b) duplication. c) inversion. d) translocation.

C

Heterochromatic regions at the ends of chromosomes are called a) centromeres. b) euchromatin. c) telomeres. d) satellites.

C

How many chromosomes does a person with Edward syndrome have? a) 45 b) 46 c) 47 d) 48

C

In a chromosomal analysis using G-banding ("routine" chromosomal analysis), a chromosome is noted to be dicentric (having two centromeres). Based on what you know about centromeric behavior, which one of the following is most likely to be true? A. An isochromosome will form in the next cell division. B. A ring chromosome will form in the next cell division. C. One of the two centromeres will be functionally suppressed because each chromosome can only "tolerate" one centromere. The mechanism of this suppression is unknown. D. The cell will die in the next cell division because this chromosome will break into multiple fragments which will be degraded. E. This dicentric chromosome will be entirely deleted from the genome.

C

In the following cytogenetic descriptions, which one suggests the highest dosage of genes from chromosome region 3q21-3q23? A. 46,XY,-3,+der(3)t(3;5)(q21;q23) B. 46,XY,del(3)(q21q23) C. 46,XY,dup(3)(q21q23) D. 46,XY,inv(3)(q21q23) E. 46,XY, t(3;5)(q21;q23)

C

Males with balanced translocations are at increased risk for which of the following conditions? A. coronary artery disease B. diabetes C. infertility D. prostate cancer

C

Of the following options, which ONE occurs in BOTH mitosis and meiosis? A. Homologs pair B. The ploidy level changes C. Sister chromatids segregate D. Two cell divisions occur E. Crossing-over occurs

C

The most common cytogenetic mechanism leading to Down syndrome is: A. Post-fertilization mitotic error B. Robertsonain translocation C. Maternal meiosis I nondisjunction D. Paternal meiosis II nondisjunction

C

The use of whole genome analysis of all gene coding regions has recently become technically feasible for clinical testing. What technology has allowed for simultaneous, rapid assessment of the entire genome at a low cost? A. DNA microarray B. Genome wide association study C. Next generation sequencing D. Polymerase chain reaction (PCR) E. Single nucleotide polymorphism (SNP) genotyping

C

When chromatids divide along the wrong plane, structures with identical arms called ____ are formed. a) ring chromosomes b) translocations c) isochromosomes d) satellites

C

Which of the following cell types is not used to examine chromosomes? a) white blood cells b) bone marrow cells c) red blood cells d) all of the above can be used

C

Which of the following individuals is MOST likely to be phenotypically normal? A. A person with the karyotype 45, X B. A person with a deletion of a single band on chromosome 4. C. A person with a pericentric inversion of chromosome 6. D. A person with the karyotype 47, XX +21 E. A person with the karyotype 46, XX,rob(14;21),+21

C

Which of the following provides the best explanation of the reproductive risk observed in carriers of a balanced reciprocal translocation? A.The translocation leads to structural abnormalities in other (previously normal) chromosomes, followed by clonal expansion. B.Nondisjunction causes the majority of gametes to have too much genetic material. C.During meiosis, unbalanced gametes may be produced. D.There is increased risk of unequal crossing over between low copy repeats. E.The translocation tends to be mitotically unstable causing it to be lost from some cells.

C

Which one of the following cytogenetic abnormalities is least likely to yield abnormal results when chromosomal microarray analysis using comparative genomic hybridization (CMA-CGH) is performed? A. 45,X/47,XXX B. 46,XY,-21,+rob(21q21q) C. 46,XY,t(3;15)(p21;q21) D. 46,XY,del(13)(q12-q22) E. 46,XY,dup(13)(q12-q22)

C

Which one of the following cytogenetic designations describes a trisomy? A. 45,X B. 46,i(Xq) C. 47,XX,+13 D. 47,XXY E. 69,XXX

C

Your pediatric patient has trisomy 13, and his parents are concerned that they might have another child with this condition. Which of the following aspects of their family history would suggest an increased recurrence risk compared to most families with a child with trisomy 13? a. Your patient is very severely affected by trisomy 13 b. There is a family history of Down syndrome c. The couple had four miscarriages before their child was conceived d. The mother is 35 years old

C

Which of the following prenatal testing methods can detect confined placental mosaicism? A. amniocentesis B. chorionic villus sampling C. fetal cells in maternal blood D. maternal blood E. percutaneous umbilical blood sampling

CVS samples chorionic villi from the placenta and can detect the mosaicism. The other tissues sampled do not include placental cells and will not allow for detection of mosaicism confined to the placenta. The correct answer is B.

A baby is born with clinical features of Down syndrome. Karyotype analysis reveals an unbalanced Robertsonian translocation. Which of the following karyotypes is consistent with this diagnosis? A. 47,XY,+21 B. 47,XX,der(13;21)(q10;q10),+21 C. 45,XY,der(14;21)(q10;q10),+21 D. 46,XX,der(21;21)(q10;q10),+21

D

A blood sample from a dysmorphic infant is sent to the cytogenetics laboratory for karyotype analysis. The laboratory report states that the child's karyotype is "46,XY,4p-". Given these results, should the laboratory perform karyotype analysis on the parents? If yes why, and if no, why not? A. No, because this karyotype is a normal variant and karyotyping the parents will give you little useful additional information B. No, because this karyotype is abnormal, and you require no additional information to make the diagnosis. C. Yes, because this karyotype may be a normal variant, and if one of the parents has the same karyotype it allows you to determine whether it is a normal variant or not. D. Yes, because this karyotype is abnormal, and karyotyping the parents will allow you to determine whether the abnormality arose de novo (is the result of a new mutation). E. Yes, because this karyotype is abnormal and karyotyping the parents will allow you to determine which parent is the carrier for a partial chromosomal deletion.

D

A couple in their late 20s who have a child with Down syndrome with a 47,XX,+21 karyotype present to you for genetic counseling. Which of the following topics should you discuss with the parents? A. Adults with Down syndrome are at risk for Huntington disease B. Parents should be karyotyped to look for Robertsonian translocations C. This disorder is tested for as part of the state newborn screening program D. The child is at risk for leukemia E. The majority of babies with Down syndrome are born to mothers over age 35

D

A couple seeks testing and counseling after they have a child with cystic fibrosis. Testing reveals that the mother is a carrier, but the father is not. How can these results be explained? a) the man tested is not the biological father b) a mutation altered the child's normal allele c) uniparental disomy (from the mother) d) all are possible explanations, additional testing is needed

D

A man is found to have 45 chromosomes because his two chromosome 21s are joined at the centromere to form a single chromosome (i.e. 21/21 Robertsonian translocation). What is the risk of a future child having Down syndrome? A. 1% B. 25% C. 50% D. 100%

D

A newborn infant is suspected to have Down syndrome. A chromosome analysis shows that 30% of the blood lymphocytes have the karyotype 46,XX and the remaining 70% have the karyotype 47,XX,+21. Which of the following events, occurring alone, is the can best explain this finding? A. Dispermy B. Error in oogenesis C. Error in spermatogenesis D. Meiotic non-disjunction E. Mitotic non-disjunction

D

A woman comes to you for counseling because of recurrent miscarriages. Which one of the following potential cytogenetic findings in her would result in the lowest likelihood of a liveborn infant with a chromosomal abnormality? A. A balanced reciprocal translocation B. A balanced 14;21 Robertsonian translocation C. A balanced 21;21 Robertsonian translocation D. A paracentric inversion E. A pericentric inversion

D

All of the following aneuploids result from female nondisjunction except a) Klinefelter syndrome. b) triplo-X. c) Turner syndrome. d) Jacobs syndrome.

D

Choose the one abnormal karyotype that is MOST likely to result from paternal meiosis II nondisjunction A. 45,X/46,XX B. 47,XXX C. 47,XXY D. 47,XYY E. 47,YYY

D

Cri-du-chat syndrome is associated with a) a missing chromosome number 5. b) an additional chromosome number 5. c) a deletion of the long arm of chromosome number 5. d) a deletion of the short arm of chromosome number 5.

D

In oogenesis, meiosis I is competed at: A. birth. B. fertilization. C. implantation. D. ovulation. E. puberty.

D

NOEY2 is a paternally expressed imprinted gene located on chromosome 1. Based on the information given, which of the following options would be associated with the HIGHEST level of NOEY2 gene expression? A. Microdeletion of the maternal chromosome (including the NOEY2 gene region) B. Microdeletion of the paternal chromosome (including the NOEY2 gene region) C. Maternal uniparental disomy (for chromosome 1) D. Paternal uniparental disomy (for chromosome 1) E. Chromosomally normal individual

D

Of the following options, which describes the location of the ribosomal RNA (rRNA) genes? A. Centromere B. Telomere C. Submetacentric long arm D. Acrocentric short arm E. Chromosome 9q21

D

On microarrays, what is the primary method used to distinguish sequence variants from one another? A. Reverse transcription of size fractionated RNA molecules B. Nuclease protection of the target sequence C. Mass differences measured by spectrometry D. Hybridization to sequence-specific DNA molecules E. Size fractionation by capillary electrophoresis

D

Our closest relative, according to karyotypes is the: a) mouse. b) domestic cat. c) gorilla. d) chimpanzee.

D

Prenatal diagnostic techniques that obtain fetal chromosomes include all but a) amniocentesis. b) fetal cell sorting. c) chorionic villus sampling. d) fluorescence in situ hybridization.

D

The most common autosomal aneuploid is a) trisomy 13. b) trisomy 15. c) trisomy 18. d) trisomy 21.

D

This structure emanates from the centromere and contacts the spindle fibers during mitosis: a) alpha satellite b) subtelomere c) euchromatin d) kinetochore

D

Which of the following karyotypes is not possible in the offspring of a translocation carrier (involving chromosomes 14 and 21) and a normal individual. a) deficient 14 or deficient 21 b) normal c) translocation Down syndrome d) all are possible outcomes

D

Which of the following karyotypes represents an UNBALANCED chromosome abnormality? A. 46,XX, t(5;20)(q22.2;q31.2) B. 45, XY, Rob(13;21)(q10;q10) C. 46,XX, ins(6;4)(q13.1;q12q24) D. 46,XY,del(10)(q23q25)

D

Which of the following pregnant women is at the MOST risk of delivering a child with Down syndrome: A. A 23 year old mother of a previous child with trisomy 21. B. A 42 year old mother of two normal children. C. A 23 year old woman who is a carrier for a 14;21 Robertsonian translocation D. A 23 year old woman who is a carrier for a 21;21 Robertsonian translocation E. A 23 year old woman whose partner carries a 13;21 Robertsonian translocation

D

Which of the following syndromes results from a chromosome deletion in a major proportion of cases? A. CHARGE syndrome B. Fragile X syndrome C. Mowat-Wilson syndrome D. Prader-Willi syndrome E. Charcot-Marie-Tooth syndrome

D

Which one of the following cytogenetc findings would be properly classified as an aneuploid state? A. 23,X B. 46,XY,inv(1)(q23q32) C. 46,XY,t(4;8) D. 48,XXYY E. 69,XXX

D

Which one of the following hypothetical risk factors gives a woman the highest risk of having a liveborn child with a chromosomal abnormality? A. Her age, which is 25 B. Her blood chromosome study result, which shows 46,XX/45,X C. Her blood chromosome study result, which shows a large paracentric inversion of chromosome 2 D. Her blood chromosome study result, which shows a large pericentric inversion of chromosome 2 E. Her family history, which shows that she has a brother with 47,XY,+21.

D

Why would one perform clustering of microarray expression data? A.To reduce the number of subjects who must be analyzed B.To minimize the number of microarrays that must be processed C.To reduce the number of statistical tests that must be performed D.To visually represent the similarities in gene expression among genes and subjects E.To group together genes that are close to one another on each chromosome

D

You are fascinated by cytogenetics and volunteer in the lab. A snowstorm prevents all the staff from getting to work and you are asked to help out by scoring a FISH experiment. The sample is an amniotic fluid from a woman who is 42 years old. Mix 1 contains probes for 13 (green) and 21 (red). Mix 2 contains X (red), Y (green) and 18 (aqua). You find the following pattern: Mix 1: 2 green, 3 red. Mix 2: 3 red, 1 green and 2 aqua. Assuming all other chromosomes are normal, the karyotype of the fetus is most likely to be: A. 48,XX,+13,+21 B. 49,XY,+13,+18,+21 C. 49,XXY,+13,+18 D. 49,XXXY,+21

D

You perform an interphase FISH analysis using a probe that detects the telomeres of all chromosomes in a cell nucleus. You see 94 fluorescent dots. Which one of the following groups of diagnoses is most compatible with this observation? A. Balanced chromosomal rearrangement states B. Monosomies C. Single gene disorders D. Trisomies E. Unbalanced chromosomal rearrangement states

D

After a normal meiosis I cell division, the resulting cells contain which of the following number of chromosomes and chromatids? A. Contains 23 chromosomes and 23 chromatids B. Contains 23 chromosomes and 46 chromatids C. Contains 46 chromosomes and 23 chromatids D. Contains 46 chromosomes and 46 chromatids E. Contains 46 chromosomes and 92 chromatids

D Keywords: meiosis Explanation: Meiosis is a reduction division. In meiosis I, homologous chromosomes replicate so each chromosome consists of two sister chromatids glued together by cohesins. In the final phases of meiosis I, homologous chromosomes segregate into separate daughter cells with each of the four resulting cells containing 23 chromosomes each of which consists of two sister chromatids.

A newborn presents with a cardiac defect, cleft palate and a hypoplastic thymus. Which of the following chromosome abnormalities is the most likely cytogenetic imbalance in this patient? A. A deletion of 1q.21.1 B. A deletion of 2q11.1 C. A deletion of 16p11.2 D. A deletion of 22q11.2 E. A deletion of 22q13.3

Deletion 22q11.2 causes VCF/DiGeorge syndrome. The three phenotypic characteristics listed are most consistent with a clinical diagnosis of 22q11.2 deletion. The correct answer is D.

A baby with several dysmorphic features and a congenital heart defect has a chromosomal microarray analysis (CMA) by comparative genomic hybridization (CGH) done to search for the cause of the patient's phenotype. In this case, the patient's DNA is labeled with a red fluorochrome, and DNA from a normal individual is labeled with a green fluorochrome. When the CMA-CGH is completed, all dots on the chip show a yellow color under fluorescence scanning, except for one dot which shows a significant green shift from the yellow. Without knowing which probe was on that dot on the chip, which one among the following diagnoses is the most likely? A. Down syndrome B. Fragile X syndrome C. Klinefelter syndrome D. Trisomy 18 E. Williams syndrome

E

A woman is a balanced carrier of a Robertsonian translocation involving chromosomes 14 and 21. Her husband is chromosomally normal. They have two children: a daughter who is a balanced translocation carrier and a son with translocation Down syndrome. Given below are genotypes for a polymorphic marker on the long arm of chromosome 21. Based on the genotypes given for three family members, predict the genotype of the translocation Down syndrome son. Mother: [1,2] Father: [2,2] Balanced carrier daughter: [1,2] Translocation Down syndrome son: ? A. 1,1 B. 1,2 C. 2,2 D. 1,1,2 E. 1,2,2

E

An infant with multiple congenital anomalies is found to carry one structurally abnormal chromosome, conferring both partial trisomy and partial monosomy. In order to provide the parents with information on the risk of recurrence in a future pregnancy, what additional testing should be considered? Choose the single best choice from the options provided. A. Gene scanning in the parents to rule out a chromosome breakage syndrome B. Gene scanning in the parents to rule out partial trisomy and/or partial monosomy C. Array CGH (comparative genome hybridization) in the parents to rule out partial trisomy and/or partial monosomy D. Routine chromosome analysis of both parents to rule out partial trisomy and/or partial monosomy E. Routine chromosome analysis of both parents to rule out a balanced chromosome translocation

E

If a proper biopsy of the inguinal mass was obtained prior to "hernia" repair in infancy, what would you most likely expect to find? a. gonadoblastoma b. intestinal tissue c. ovarian tissue d. ovotesticular tissue e. testicular tissue

E

Only a few specific autosomal trisomies are seen in live born infants. Of the following options, the best explanation for this is: A.Only a few specific chromosomes are at risk to undergo nondisjunction during meiosis. B.Nondisjunction occurs primarily in spermatogenesis, and the sperm produced are unlikely to fertilize the egg. C.The autosomal trisomies are largely underdiagnosed, since most affected infants are phenotypically normal. D.Since autosomal monosomy is so much more common, the autosomal trisomies are rare. E.Although nondisjunction may involve any chromosome, most autosomal trisomies are lethal.

E

Using a probe specific for the centromere of chromosome 21, a fluorescence in situ hybridization (FISH) study was performed on a patient sample. 3 dots of fluorescence were seen in each of 100 interphase chromosome spreads. Other than Down syndrome due to trisomy 21, which one of the following diagnoses is also compatible with this finding? A. Down syndrome due to Robertsonian translocation between chromosomes 14 and 21 B. Down syndrome due to trisomy 21 mosaicism C. Monosomy 21 D. Paracentric inversion of chromosome 21 E. Triploidy

E

Using a probe that detects the centromeres of all chromosomes in a fluorescence in situ hybridization study, how many dots of light would you expect to see in most patients with Down syndrome? A. 2 B. 3 C. 45 D. 46 E. 47

E

Which of the following is the most common cause of triploidy? A. Nondisjunction in maternal meiosis I B. Nondisjunction in maternal meiosis II C. Fertilization of an aneuploid egg by a normal sperm D. Fertilization of a normal egg by an aneuploid sperm E. Fertilization of a normal egg by two normal sperm

E

Which of the following would not routinely be detected by comparative genomic hybridization analysis performed on a patient's blood sample? A. Down syndrome B. Trisomy 18 C. Williams syndrome D. Klinefelter syndrome E. Balanced translocation

E

Which one of the following DNA repeat elements protects a chromosome from being inserted into another chromosome through random recombination? A. a-satellites B. Centromeres C. Microsatellites D. Minisatellites E. Telomeres

E

Which one of the following cytogenetic abnormalities is most readily detected by comparative genomic hybridization using chromosomal microarray? A. 45,-21,-21,+rob(21;21) B. 46,XX/46,XY (ratio of 95:5) C. 46,XX,inv(8) D. 46,XX,t(5;7)(q12;p22) E. 48,XXYY

E

Which one of the following denotes a pericentric inversion? A. 46, -X, +i(Xq) B. 46, XX, del(5)(p11) C. 46, XX, dup(5)(p13;p22) D. 46, XY, inv(1)(p21;p36) E. 46, XY, inv(1)(p21;q21)

E

Which one of the following is most likely to be a consequence of dispermy? A. 45,X/46,XY B. 46,XX/47,XX,+21 C. 46,XY,t(7;15) D. 47,XY,+21 E. 69,XXX

E

Which of the following microarray confirmation methods can allow the cytogeneticist to determine the mechanism of an imbalance detected on comparative genome hybridization studies? A. Fluorescence In Situ Hybridization (FISH) B. Junction fragment PCR C. Multiplex ligation-dependent probe amplification (MLPA) D. Quantitative PCR E. Targeted microarray for the abnormal region

Only FISH can show the localization of the signal on chromosomes and allow for a determination of the mechanism for the imbalance. The correct answer is A

During meiosis, homologs must pair in order for recombination to occur. Which of the following events allows optimal pairing and normal segregation: A. One or more chiasma per chromosome B. Two or more chiasma per chromosome arm C. Distal position of chiasma on chromosome arm D. Medial position of chiasma on chromosome arm E. Centromere pairing of chromosomes

Optimal pairing includes one chiasma per chromosome arm, or two per chromosome. The correct answer is A.

Meiotic recombination is necessary for genetic diversity and rates of genetic recombination are different in males than females and for different chromosomal regions. The highest rate of recombination is observed in which of the following situations? A. in females compared to males near centromeres B. in males compared to females near centromeres C. in males compared to females in the middle of each chromosome arm D. near centromeres compared to near telomeres E. near telomeres compared to near centromeres

Overall, recombination rates in human females are significantly higher (~50%) than males, except near telomeres, where male recombination rates are higher than female. Human recombination is about twice as high as that in mouse, perhaps due to our biarmed chromosomes compared to all telocentric chromosomes in mice (remember the obligatory 1 crossover per chromosome arm for stable pairing and segregation). Recombination is suppressed near centromeres, and increases greatly near telomeres in both males and females (but more so in males). The correct answer is E..

An MRI shows lissencephaly in your patient, however the patient does not have any dysmorphic facial features. Which of the following is the most likely mutation? A. Point mutation within the LIS1 gene coding region. B. Terminal deletion of 17p which includes the LIS1 gene C. Terminal deletion of 17q which includes the LIS1 gene D. Terminal duplication of 17p which includes the LIS1 gene E. Triplet repeat expansion involving the LIS1 gene

Point mutations within the LIS1 gene cause Isolated Lissencephaly syndrome. These individuals can only exhibit lissencephaly without the more dysmorphic features that are associated with Miller-Dieker syndrome, which is caused by larger deletions of 17p. The correct answer is A

Triploidy is the result of three copies of each human chromosome and is one of the most common causes of spontaneous miscarriage. Which of the following occurrences is the most common mechanism by which triploidy arises? A. chimerism B. duplication of an entire maternal haploid chromosome set C. one egg fertilized by two sperm D. tetraploid conception with loss of one copy of each chromosome E. two eggs fertilized by one sperm

Polyspermy is the most common cause of triploidy. Chimerism may caused by the fusion of two embryos and differs from mosaicism. The other options are not likely to be observed. The correct answer is C.

G-banding has been the preferred method for cytogenetic analysis since the late 1960s. The underlying DNA content corresponds to the staining pattern observed by G-banding. Which of the following descriptions details the difference(s) between G-negative bands and G-positive bands? A. G-negative bands are more gene rich than G-positive bands B. G-positive bands are GC rich regions and are early replicating C. G-negative bands are AT rich and are late replicating D. G-negative bands are GC rich and are late replicating E. G-positive bands are more gene rich than G-negative bands

R-bands are the reverse of G-bands, so there are the same number of each. G-positive bands are AT-rich and relatively later replicating. The correct answer is A

If you were a T-lymphocyte destined for cytogenetic analysis, some of the treatments you would experience along the way (in correct order) are: A. Hypotonic solution, acetic acid, Giemsa, trypsin B. Hypotonic solution, lysis buffer, trypsin, Giemsa C. Phytohemagglutinin, hypotonic solution, fixative, Colcemid, Giemsa D. Phytohemagglutinin, Colcemid, hypotonic solution, fixative, trypsin E. Trypsin, acetic acid, hypotonic solution, Giemsa

T-lymphocytes are stimulated to a blast phase with the red kidney bean extract phytohemagglutinin (PHA). After 48-72 hours, a mitotic poison such as Colcemid or colchicine is used to block spindle formation and attachment to "arrest" cells in mitosis, a hypotonic treatment is used to swell the cells, they are fixed in 3:1 methanol:acetic acid, put onto slides, and then most often treated with trypsin prior to Giemsa staining to produce G-banding patterns. The correct answer is D.

A young woman with severe mental retardation, short stature, and other malformations has a karyotype of 45,X/46,X,r(X). Which of the following explanations is most likely to account for the constellation of clinical features noted above? A. Both X chromosomes are likely to be active in the cells with 46 chromosomes. B. The normal X is likely to be inactive in most or all of the cells with 46 chromosomes. C. The ring X is likely to be acentric explaining its absence in the 45,X cell line. D. The ring X is likely to be inactive in most or all of the cells with 46 chromosomes. E. The XIST gene will almost certainly be present on the ring X chromosome.

The abnormal phenotypes seen in association with mosaic karyotypes of the type indicated are associated with failure of X inactivation. This is usually also associated with lack of expression of the XIST gene. This means that both the normal X and the ring X are likely to be active. The XIST gene is considerably more likely to be deleted than to be present on the ring X, although deletion of the X inactivation center may be more pertinent than deletion of the XIST gene. As mentioned above, both X chromosomes are likely to be active. The ring is not likely to be acentric. The correct answer is A.

Chromosomal rearrangements can result from a variety of mechanisms during meiosis or mitosis. Which of the chromosome rearrangements listed below always involves at least two chromosomes? A. Balanced Translocation B. Duplication C. Interstitial deletion D. Isochromosome E. Pericentric inversion

The correct answer is A. Keywords: structural chromosomal abnormalities Explanation: A balanced translocation in the only structural chromosomal abnormality in the list provided to involve at least two chromosomes. All other listed abnormalities involve only one chromosome.

Aneuploidies typically result from meiotic errors but the specific missing or additional chromosome is not necessarily derived from the maternal or paternal gametes at an equal rate. Which of the following aneuploidies virtually always arises as a result of maternal meiotic error? A. 45,X B. 47,XY,+16 C. 47,XX,+21 D. 47,XXX E. 47,XXY

The correct answer is B. Keywords: aneuploidy, nondisjunction Explanation: Trisomy 16 is a prenatal lethal aneuploidy due to a maternal meiosis I nondisjunction in 100% of cases. Turner syndrome (45,X) is 70% paternal and 30% maternal in origin. Trisomy 21 is 92% maternal and 8% paternal in origin. 47,XXX is 90% maternal and 10% paternal in origin. Klinefelter syndrome (47,XXY) is 54% maternal and 46% paternal in origin.

41. A phenotypically normal person carries a reciprocal balanced translocation between two autosomes. When segregation occurs in this individual during meiosis I, which of the following statements regarding the eventual offspring appropriately associates the genotype with the expected phenotype? A. Alternate segregation always leads to a normal karyotype with a normal phenotype B. Alternate segregation can lead to an abnormal karyotype with a likely normal phenotype C. Adjacent-1 segregation leads to a normal karyotype with an abnormal phenotype D. Adjacent-1 segregation leads to an abnormal karyotype with a likely normal phenotype E. Adjacent-2 segregation leads to a normal karyotype with a likely normal phenotype

The correct answer is B. Keywords: segregation of a balanced translocation Explanation: Alternate segregation can produce either normal or balanced translocation in the offspring. If the carrier is phenotypically normal, then the offspring carrying the same balanced translocation will most likely be phenotypically normal. Adjacent-1 segregation can only produce the unbalanced versions of the translocation in the offspring with an abnormal phenotype. Adjacent-2 segregation is very rare and will also produce unbalanced products that are phenotypically abnormal.

Imprinting plays a role in determining the phenotype of many different conditions. In which of the following groups of disorders can all of the diagnoses be associated with imprinting as a major determinant of phenotype? A. Angelman syndrome, Prader-Willi syndrome, DiGeorge syndrome B. Ovarian teratoma, Trisomy 13 mosaicism, Beckwith-Wiedemann syndrome C. Triploidy, Prader-Willi syndrome, ovarian teratoma D. Triploidy, Williams syndrome, Beckwith-Wiedemann syndrome E. Prader-Willi syndrome, Trisomy 8 mosaicism, Russell-Silver syndrome

The correct answer is C. Keywords: imprinting Explanation: Imprinting plays a major role in the phenotype of Angelman syndrome, Prader-Willi syndrome, Beckwith-Wiedmann syndrome, Russell-Silver syndrome, ovarian teratoma, and triploidy. Imprinting does not play any role in the phenotype of Trisomy 13 and Trisomy 8 mosaicisms, DiGeorge syndrome, and Williams syndrome.

Recurrent microdeletions and their reciprocal microduplications are the result of which molecular mechanism? A. Allelic homologous recombination (AHR) B. Fork stalling and template switching (FoSTeS) C. Non-allelic homologous recombination (NAHR) D. Non-homologous end joining (NHEJ) E. Replication slippage

The correct answer is C. Keywords: molecular mechanisms, recurrent CNVs Explanation: Recurrent microdeletions/microduplications are caused by NAHR, which is mediated by the homologous flanking segmental duplications. FoSTeS, NHEJ, and replication slippage, all result in non-recurrent copy number changes. AHR is a normal recombination mechanism that does not result in copy number changes.

A patient carries an interstitial deletion in the proximal region of the long (q) arm of the paternal homologue of chromosome 15 [del(15)(q11.2q13.1)]. This patient is expected to present with which of the following disorders? A. Angelman syndrome B. DiGeorge syndrome C. Miller-Dieker syndrome D. Prader-Willi syndrome E. Williams syndrome

The correct answer is D. Keywords: microdeletion, genomic disorders Explanation: 15q11.2q13.1 deletion on the paternal chromosome 15 causes Prader-Willi syndrome, whereas the same deletion on the maternal chromosome 15 causes Angelman syndrome. DiGeorge syndrome is due to a 22q11.2 deletion. Miller-Dieker syndrome is due to a 17p13.3 deletion. Williams syndrome is due to a 7q11.23 deletion.

The mammalian somatic cell cycle is approximately 24 hours in length. Which of the following phases of the cell cycle requires the most time? A. G1 B. S C. G2 D. Interphase E. Mitosis

The correct answer is D. All of the phases of mitosis take approximately one hour.

Which of the following recurrent translocations is diagnostic of chronic myeloid leukemia (CML)? A. t(8;21)(q22;q22) B. t(15;17)(q22;q21) C. t(12;21)(p13;q22) D. t(4;11)(q21;q23) E. t(9;22)(q34;q11.2)

The correct answer is E. Keywords: cancer cytogenetics, leukemia Explanation: The t(9;22)(q34;q11.2) is diagnostic of CML and a subset of B-precursor ALL. The t(8;21)(q22;q22) is diagnostic of AML-M2. The t(15;17)(q22;q21) is diagnostic of acute promyelocytic leukemia (AML-M3). The t(12;21)(p13;q22) is diagnostic of a subset of B-precursor ALL. The t(4;11(q21;q23) is diagnostic of a subset of B-precursor ALL observed mostly in infants.

Carriers of balanced structural chromosomal rearrangements are at risk of having offspring with an unbalanced chromosome complement. Which of the following statements is true regarding the risk of unbalanced offspring? A. Carriers of small pericentric inversions have higher risk than large pericentric inversions B. Carriers of paracentric inversions have higher risk than pericentric inversions C. Carriers of balanced autosomal translocations have a 75% risk of having unbalanced offspring D. Female carriers of the 21;21 Robertsonian translocation have a 50% risk of having trisomy 21 offspring E. Female carriers of the 14;21 Robertsonian translocation are at higher risk than male carriers

The correct answer is E. Keywords: risk in carriers of balanced chromosomal abnormalities Explanation: The risk of having a trisomy 21 offspring in female carriers of the 14;21Robertsonian translocation is ~10-15%, whereas the risk in male carriers is ~0-2%. Carriers of large pericentric inversions have higher risk than small pericentric inversions. Carriers of pericentric inversions have higher risk than paracentric inversions. Carriers of balanced autosomal translocations have a 10-15% risk of having unbalanced offspring. Carriers of the 21;21 Robertsonian translocation have a 100% risk of having trisomy 21 offspring.

A child is born with a partial deletion and partial duplication for the same chromosome. Which of the following chromosomal abnormalities represents the likely parental chromosome abnormality predisposing to this occurrence? A. Balanced insertion B. Balanced reciprocal translocation C. Balanced Robertsonian translocation D. Paracentric inversion E. Pericentric inversion

The correct answer is E. Keywords: structural chromosomal abnormalities Explanation: A pericentric inversion is the only structural chromosome abnormality that can predispose to a terminal duplication on one chromosome arm and a terminal deletion on the other chromosome arm in the offspring.

The historical milestones in cytogenetics mark exciting intervals in the development of the field of clinical genetics. Which of the following series of events follows the chronological order in which these milestones were attained? A. Hypotonic treatment of cells > Correct chromosome number is 46 > Y chromosome identified in humans > Chromosome banding techniques>Fragile sites and fragile X syndrome B. Correct chromosome number is 46 >Hypotonic treatment of cells > Y chromosome identified in humans > Chromosome banding techniques> Fragile sites and fragile X syndrome C. Y chromosome identified in humans >Hypotonic treatment of cells > Correct chromosome number is 46 > Chromosome banding techniques> Fragile sites and fragile X syndrome D. Hypotonic treatment of cells > Y chromosome identified in humans> Correct chromosome number is 46 > Chromosome banding techniques> Fragile sites and fragile X syndrome E. Y chromosome identified in humans> Hypotonic treatment of cells > Correct chromosome number is 46 > Fragile sites and fragile X syndrome> Chromosome banding techniques>

The discovery of the Y Chromosome and the XX/XY mechanism of sex determination in humans was by T. S. Painter in 1923, hypotonic treatment of cells by T. C. Hsu in 1953, the correct chromosome number by Tjio and Levan in 1956, chromosome banding techniques in 1969/70, and fragile sites and fragile X in the late 70s. The correct answer is C.

A newborn presents with microcephaly, hypotonia, and a high-pitched cat-like cry? Which of the following cytogenetic abnormalities is most likely to be found on chromosomal analysis? A. 4p deletion B. 5p deletion C. 5q deletion D. 8p deletion E. 11p deletion

The features described fit Cri du Chat syndrome which typically results from terminal deletion 5p from band 5p15.2 to 5pter. 4p- syndrome results in Wolf-Hirschorn syndrome. 5q- and 8psyndromes do not have alternative names. 11p- deletion is associated with WAGR syndrome. The correct answer is B.

A child is born with a partial deletion and partial duplication involving the same chromosome. Which of the following parental chromosomal abnormalities is most likely to lead to this occurrence? A. balanced reciprocal translocation B. balanced Robertsonian translocation C. isochromosome D. pericentric inversion E. paracentric inversion

The occurrence of a deletion and duplication involving the terminal portions of the same chromosome is typically the result if one parent carries a pericentric inversion. This occurs if there is a cross-over within the inversion loop at meiosis. The correct answer is D.

A 2-year-old boy presents with a history of retinoblastoma, dysmorphic features and developmental delay. Which of the following molecular abnormalities is the most likely cause of his clinical findings? A. Nonsense mutation in the RB1 gene. B. Missense mutation in the RB1 gene. C. RB2 gene mutation D. Contiguous gene deletion of 13q14 E. Contiguous gene deletion of Xq27.3

The patient has additional clinical features (dysmorphic features and developmental delay) toretinoblastoma, suggesting a larger deletion that includes more genes than just the RB1 gene. The correct answer is D.

A middle-aged couple visits prenatal clinic for preconception counseling. Based on the wife's age their risk of having a child with Down syndrome is increased. The genetic counselor explains that even if their pregnancy were to result from a trisomy 21 conception there is a reduced likelihood that the pregnancy would lead to a liveborn infant. Which of the following probabilities best represents the likelihood that a trisomy 21 conception will result in a liveborn infant? A. 1% B. 20% C. 70% D. 90% E. 100%

The probability that a trisomy 21 conception will result in live birth is approximately 20%. The correct answer is B.

Which of the following chromosome abnormalities is mostly likely constitutional? A. t(8;21)(q22;q22) B. t(11;22)(q23;q11.2) C. del(5)(q22q33) D. inv(16)(p13q22) E. t(15;17)(q22;q21)

the 11;22 translocation is the most common non-Robertsonian translocation observed in constitutional cytogenetic studies. The correct answer is B.