Define cytogenetics.
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The study of metaphase chromosomes in the cell, including genomic structure, function, variation, and their role in disease and heredity.
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Define cytogenetics.
The study of metaphase chromosomes in the cell, including genomic structure, function, variation, and their role in disease and heredity.
What is the primary focus of constitutional cytogenetics?
The diagnosis of heritable genetic abnormalities in children, adults, pregnancy, and fetal loss.
What is the primary focus of cancer cytogenetics?
The detection of acquired or somatic genetic abnormalities for diagnosis, prognosis, therapy, and monitoring of many types of cancer (especially hematologic).
What are the three key features scientists use to identify chromosomes?
Centromere position, banding pattern, and size.
What are the names of the short and long arms of a chromosome?
The p arm (short) and the q arm (long).
What term describes a chromosome where the centromere is located in the middle, making both arms approximately equal in length?
Metacentric
What term describes a chromosome where the centromere is off-center, resulting in one arm being clearly shorter than the other?
Submetacentric
What term describes a chromosome where the centromere is located very near one end, resulting in a very small p arm often containing a stalk and satellite?
Acrocentric
Which human chromosomes are classified as acrocentric?
Chromosomes 13, 14, 15, 21, and 22.
What is the term for the stalks on acrocentric chromosomes that associate during interphase to form the nucleolus?
Nucleolar organizing regions (NORs).
What are the primary functions of the nucleolus?
rRNA transcription and processing, and ribosome assembly.
How are chromosomes 1 and 3 classified according to Denver nomenclature?
Metacentric.
What are the general characteristics of Group D chromosomes (13-15)?
Medium-sized, acrocentric with satellites.
According to Denver nomenclature, which group includes the Y chromosome?
Group G (21, 22, Y).
What characteristic do homologous chromosomes share regarding their appearance after staining?
They share the same banding pattern.
What is the standard procedure for G-banding in cytogenetic laboratories?
Trypsin digestion followed by Giemsa staining.
What type of DNA is found in dark G(+) bands?
AT-rich DNA.
For what specific purpose is R-banding useful?
Studying the telomeres of chromosomes (which are hard to see on G-banded preparations).
What is an ideogram in the context of human cytogenetics?
A schematic representation of a standardized set of chromosomes with G-banding, used as a reference for size and banding patterns.
What is the minimum resolution of standard karyotyping for identifying chromosomal changes?
3-5 Mbp.
How can higher banding resolution (e.g., 850 bands vs 400 bands) be achieved?
Staining chromosomes in prometaphase (when they are less condensed).
From which tissue types can cells be obtained for chromosome analysis?
Bone marrow (directly) or stimulated lymphocytes, fibroblasts, and fetal cells (after culture).
What is the role of phytohemagglutinin (PHA) in the preparation of a karyotype?
To stimulate lymphocytes to divide.
What is the function of Colchicine (or Colcemid) in chromosome preparation?
It acts as an anti-mitotic drug that prevents microtubule polymer elongation, blocking cells in metaphase.
What is the purpose of using hypotonic saline during cell harvest for cytogenetics?
To cause cell swelling, facilitating chromosome spreading.
What is the distinction between a karyotype and a karyogram?
Karyotype is a verbal description using symbols; Karyogram is an organized micro-photograph of the chromosomes.
Which technique uses fluorescently labeled single-stranded probes to detect the presence or absence of specific DNA sequences?
Fluorescence in situ hybridization (FISH).
Explain the basic principle of Array Comparative Genomic Hybridization (Array-CGH).
Competitive hybridization of test (patient) and reference DNA to a microarray of mapped clones to detect copy number variations (CNV).
What type of chromosomal abnormalities cannot be detected by Array-CGH?
Balanced abnormalities, such as inversions or balanced translocations.
In Array-CGH, what does a red signal intensity greater than the green signal intensity (RED > GREEN) typically indicate?
The patient has a duplication at that genomic location.
Define euploid.
A cell having one or more complete sets of chromosomes (e.g., n, 2n, 3n).
Define aneuploid.
A cell having one or more chromosomes extra or missing from the normal full euploid set (e.g., 2n+1, 2n-1).
What is the most common cause of human triploidy (3n)?
Dispermy (fertilization of an egg by two sperm).
By what mechanism does tetraploidy (4n) typically arise?
Endomitosis (DNA replication without subsequent cell division).
What are the two primary mechanisms leading to aneuploidy?
Nondisjunction and anaphase lagging.
What occurs during nondisjunction?
Failure of homologous chromosomes (Meiosis I) or sister chromatids (Meiosis II/Mitosis) to separate properly.
Describe the process of anaphase lag.
A chromosome or chromatid movement is delayed in anaphase, fails to be included in the new nucleus, and eventually degrades.
What is the clinical outcome for autosomal monosomies in humans?
Invariably lethal at the earliest stages of embryonic life.
Which three autosomal trisomies can survive to term in humans?
Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13).
What is the standard karyotype for Down syndrome?
47,XX,+21 or 47,XY,+21.
What is the most frequent cause (90% of cases) of trisomy 21?
Maternal nondisjunction during the first meiotic division.
What factor is strongly associated with an increased incidence of Down syndrome?
Increasing maternal age.
List three common physical features of Patau syndrome (Trisomy 13).
Cleft lip/palate, microcephaly, and polydactyly.
Which autosomal trisomy is associated with Edwards syndrome and has a survival rate of maximum one year?
Trisomy 18 (maximum 1 year).
What is trisomy rescue?
In a nonviable trisomic embryo, the chance loss of one extra chromosome by anaphase lag produces a disomic cell that can form a viable embryo.
What is the karyotype for Klinefelter syndrome?
47,XXY.
List common physical features of Klinefelter syndrome.
Tall stature, feminized physique, gynecomastia, and testicular atrophy/infertility.
What is the most common karyotype for Turner syndrome?
45,X.
What are the characteristic features of Turner syndrome?
Short stature, webbed neck (pterygium colli), underdeveloped breasts, and streak gonads (infertility).
What is the karyotype for Double Y condition?
47,XYY.
What is the primary physical characteristic of individuals with 47,XYY?
Taller than average height.
What is the karyotype for Trisomy X (Triplo X condition)?
47,XXX.
What causes the 46,XX male condition?
Translocation of the SRY gene (mammalian Y-chromosomal testis-determining gene) to an X chromosome.
Define mosaicism.
The presence of two or more cell lineages with different chromosomal content arising from a single zygote in one individual.
Define chimera.
An organism derived from more than one zygote (e.g., through fusion of zygotes or cell exchange).
What treatment is required for females with Turner syndrome?
Hormone replacement (to develop female phenotype).
Besides dispermy, how else can polyploidy (like tetraploidy) be caused?
Mitotic failure or fusion of two diploid zygotes.
Which sex chromosome monosomy is always lethal and never viable?
45,Y.
Why does having extra X chromosomes (e.g., in 47,XXX or 47,XXY) have fewer ill effects than autosomal trisomies?
X-inactivation (ensures each cell has only one functional X).
What symptom tends to worsen in rare variants of Klinefelter syndrome as the number of extra X chromosomes increases (e.g., 48,XXXY or 49,XXXXY)?
Intellectual disability (IQ is lower with more X chromosomes).
What is the primary cause of structural chromosomal rearrangements?
Chromosome breaks.
What are the two types of chromosomal inversions, and how do they differ?
Paracentric inversion (same arm) and pericentric inversion (different arms, includes centromere).
Define chromosomal deletion.
Loss of a terminal or interstitial segment of a chromosome.
In the karyotype 46,XY,del(4)(p16.3), what type of deletion is represented?
Terminal deletion (breakpoint at 4p16.3).
What is a chromosomal duplication?
Part of a chromosome is copied abnormally, resulting in extra genetic material.
How is a ring chromosome formed?
Two breaks occur on different arms of a chromosome, and the broken ends fuse together.
What is an isochromosome?
An abnormal symmetrical chromosome consisting of two identical arms (either two p arms or two q arms).
What is the fate of an isochromosome X (iXq) in a cell?
It always becomes a Barr body (inactivated).
What is the genetic dosage consequence for a female with 46,X,iXq (Turner syndrome variant)?
The person is monosomic for the lost short arm genes and trisomic for the long arm genes.
Why are ring chromosomes problematic during cell division?
They are unstable during cell division and can form interlocking or fused rings.
What is a terminal deletion?
Deletion of the distal part of a chromosome arm.
What is an interstitial deletion?
A deletion within the arm of a chromosome (two breakpoints).
What happens to a chromosome segment during an inversion?
The segment of the chromosome is present in the opposite orientation to normal.
Define haploinsufficiency.
A locus requires more gene product than what is produced by a single functional allele to maintain a normal phenotype.
What is a marker chromosome (+mar)?
A chromosome of unknown origin, often unidentified in classical karyotyping.
What is a reciprocal translocation?
The exchange of segments between two non-homologous chromosomes.
Define a balanced translocation.
A translocation where pieces of chromosomes are rearranged but no genetic material is gained or lost.
What is a Robertsonian translocation?
A translocation between the short arms of two acrocentric chromosomes, where the short arms are lost and the long arms fuse at the centromere.
What happens to the acentric fragment formed during a Robertsonian translocation?
It is lost during mitosis but has no phenotypic effect (due to redundant rRNA genes on other acrocentric chromosomes).
What is the typical karyotype of a balanced Robertsonian translocation carrier involving chromosomes 14 and 21?
45,XX,-14,-21,rob(14;21).
What is the practical risk of having a child with Down syndrome if one parent is a balanced rob(14;21) carrier?
10% if the mother is the carrier; 5% if the father is the carrier.
What specific chromosomal abnormality is the hallmark of Chronic Myeloid Leukemia (CML)?
The Philadelphia chromosome (resulting from t(9;22)).
What is non-allelic homologous recombination (NAHR)?
Recombination between misaligned, highly homologous but non-allelic DNA repeats (low-copy repeats) on the same or different chromosomes.
What does NAHR between repeats in the same orientation produce?
Deletions or duplications of the sequence between the repeats.
What chromosomal abnormality causes Cri-du-chat syndrome?
Deletion of a variable portion of the short arm of chromosome 5 (5p-).
Which chromosomal region is deleted in DiGeorge syndrome?
22q11.21 region deletion (approx. 30 genes).
What are the clinical symptoms of DiGeorge syndrome?
Thymus aplasia (immunodeficiency), cleft palate, hypocalcaemia, and great vessel abnormalities (e.g., Fallot tetralogy).
What is the location of the microdeletion in Williams-Beuren syndrome?
7q11.23.
In Williams-Beuren syndrome, the deletion of the ELN gene is associated with which clinical features?
Connective-tissue abnormalities and cardiovascular disease (elastin insufficiency).
Describe the characteristic social behavior of individuals with Williams-Beuren syndrome.
They are extremely social ("true social creatures"), like to make friends, and talk to strangers ("cocktail party personality").
