Cytogenetics Review Questions
Unit 1
List the three broad categories of clinical indications for chromosomal analysis.
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Prenatal, Constitutional, Cancer/Acquired |
Which family members should have chromosomal analysis?
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List 5 prenatal indications for cytogenetics analysis.
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What are the indications for chromosomal analysis of products of conception?
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Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results
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What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?
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List 8 standard techniques for cytogenetics analysis.
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List 5 Molecular cytogenetics techniques.
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What is g-banding?
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Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome. |
Outline the general procedure for cytogenetics study.
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Broadly what at the three main morphological groups of chromosomes?
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Metacentric, acrocentric, submetacentric. |
What are the 4 minimum items included in a standard banding nomenclature?
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What are the clinical indications for an individual to have chromosomal analysis?
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What is q-banding?
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Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome. |
What is R-banding?
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Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding. |
What is C-banding?
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C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y |
What is NOR?
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NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes) |
List the metacentric chromosomes.
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List the submetacentric chromosomes.
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List the acrocentric chromosomes.
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What is Bloom syndrome?
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Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[1]] |
What is SCE (Sister chromatid exchange?
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SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids. |
What is DAPI staining?
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DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y. |
Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.
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Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase. |
Unit 2
Describe the 4 steps of mitosis.
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Prophase, metaphase, anaphase, telophase |
List the 8 steps of meiosis.
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What is the main difference between constitutional and acquired chromosome anomalies.
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Constitutional affects the whole patient, acquired usually limited to 1 organ. |
What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?
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{{{2}}} |
What is meant by a homogeneous chromosomal anomaly?
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Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired. |
What is meant by a mosaic chromosomal anomaly?
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Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired. |
What are chromosomal polymorphisms?
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Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere. |
List 3 known chromosomal polymorphisms, according to ISCN 2013.
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Classify numerical abnormalities of chromosomes.
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What are the four main types of abnormalities in chromosome structure?
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What is the key difference between a balanced and an unbalanced chromosomal rearrangement?
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Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype. |
List three types of balanced chromosomal rearrangements.
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Translocation, inversion, insertion. |
List three unbalanced numerical chromosomal rearrangements.
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trisomy, monosomy, multiploidy |
List 5 structural unbalanced chromosomal rearrangements.
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What is the karyotype for a female infant with cri-du-chat?
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46,XX,del(5)(p15.1) |
Unit 3
What is FISH?
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FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei. |
When is interphase FISH more helpful than metaphase?
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Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue. |
What is the approximate resolution of cytogenetic FISH?
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3-5Mb |
What are the three types of FISH probes?
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List 7 applications of FISH technology?
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List 5 microdeletion syndromes.
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Briefly describe Cri-du Chat Syndrome
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Describe 3 mechanisms by which uniparental disomy occurs.
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What is imprinting?
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Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation. |
Which chromosomes are known to have imprinted genes?
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Chromosomes 6,7,11,14,and 15. |
Describe Prader-Willi Syndrome.
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Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene |
Briefly describe Williams Syndrome.
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{{{2}}} |
Describe DeGeorge Syndrome.
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What is SKY?
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A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour. |
What kinds of chromosomal transformations is SKY used for?
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What are thelimitations of SKY?
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1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar |
Explain the basic principle of Comparative Genomic Hybridization.
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References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome. |
How do CGH arrays work?
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CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe. |
Unit 4
Miscellaneous
What is Allerdice or Sandy Point Syndrome?
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It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays. |
What is the most common robertsonian translocation?
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Translocation between the long arms of 13 and 14. |
What is the most common non-robertsonian translocation?
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t(11;22)(q23;q11) |
What is a marker chromosome?
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A structurally abnormal chromosome in which no part can be identified cytogenetically. |
What is the most common chromosomal abnormality in humans?
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Aneuploidy - about 5% of pregnancies. |
What is the most common cause of triploidy?
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Dispermy in 60% |
What is the recurrence risk for parents of Down's syndrome child with a "free chromosome"?
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1% |
List 5 features of Trisomy 8.
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List 5 features of Trisomy 9.
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List 5 features of Trisomy 13.
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List 5 features of Trisomy 14.
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List 5 features of Trisomy 18.
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List 5 features of Trisomy 21.
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What is the most common outcome of a pregnancy when the parent has a balanced translocation?
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Misscarriage |