Cytogenetics and Aneuploidy Flashcards
Physicians from ___, ___, ___, ____ and ___ all often refer patients to undergo cytogenetic studies
Neonatal
Reproductive health
Neurology
Endocrinology
Hematology/oncology
3 main methods of cytogenetics:
G banded
FISH fluorescence in Situ hybridization
Chromosomal microarrays
Only during ____ are chromosomes visible under the light microscope for G banding. You must have ____ cells
Mitosis
Dividing
Common cells that can undergo Gbanded studies are:
White blood cells, skin, bone marrow
Cells can also be stimulated by ____ to begin dividing
Mitogen
Cells are Gbanded in _____ and treat the slide with ___ and ____ stain
Mitosis
Protease
Giemsa
Each ____ has a unique G banding pattern that is ____ between individuals
Chromosome
Constant
The chromosomes are paired and lined up into a _____
Karyotype
When looking at a chromosome under G banding it looks like there is only one, however we are looking at ___ ___
Sister chromatids
Writing karyotypes:
Typical ____: 46, XX
variant karyotype: 47, XY, +21
Female
____ = the short arm
____ = the long arm
p
q
Each G band typically encompasses millions of bass pairs of DNA. For example, 10p13 has _____ base pairs of DNA encompassing ____ genes. Therefore, when there is a visible chromosome abnormality involving loss or gain of 1 or more Gbands, there are ____ clinical issues
5,100,000
40
Multiple
The limitations of Gbanding is that you must have a ___ cell and we can visualize only ____ regions
Dividing
Large
FISH addresses the limitations of G banding. Don’t need a ___ cell and we can see ____ deletions
Dividing
Smaller
FISH:
Obtain DNA from an interest on chromosome which will serve as the ____. Label the DNA with ____ dye. Place cell on a slide and treat with heat to ____ the DNA. The fluorescent dye will find and bond it’s complementary base pairs in the patients DNA. We then ___ the hybridized (binded) fluorescent spots
Probe
Fluorescent
Denature
Count
3 copies of 13, instead of 2
Limitations of FISH:
Only looking at a ____ region of each chromosome. Can only look at a few ___ per assay.
Small
Probes
Trisomy 21 is Down syndrome. 40 to 50% of children with Down syndrome will have a structural ____ defect in the atrioventricular canal. Other Common associates are ____
Heart
Hearing loss
Hypothyroidism
Duodenal atresia
Hypotonia- low muscle tone
Early onset of leukemia
______ is abnormal segregation of chromosomes (meiosis I) or sister chromatids (meiosis II, mitosis) and causes trisomy 21. 90% of the time it arises by ____ Nondisjunction error during oogenesis
Nondisjunction
Meiosis I
Review
Two homologs should be separating, but both go in to one cell
Down syndrome occurs in _____ births. Chance increases as the mother gets older
1/800
Trisomy 21 is one of the only _____ trisomies that is compatible with life into adulthood
Autosomal
Trisomy 13 and trisomy 18 are the only other trisomies that may be ____.
Live born
Trisomy 13 causes ____ with incomplete development of the forebrain. Cleft lip is common. ____ of hands and feet. Severe cognitive disabilities. Cardiac anomalies. Abnormal genitalia
Holoprosencephaly
Polydactyly
Most autosomal trisomies will result in ____.
Miscarriage
Chromosome abnormalities account for approximately ___% of miscarriages. Trisomy 16 has strong association with advanced maternal age and most commonly causes miscarriages
50
____ of ___ is a chromosome study performed on tissue from the miscarriage, from the placenta.
Products of conception
Sometimes an autosomal trisomy can be seen in a live born if it is in ____ state with a non trisomic cell line
Mosaic
_____ is when two or more populations of cells are identified, each has a different karyotype. Usually associated with a ____ severe phenotype but cannot tell what the different distribution of cell lines is in different tissues
Mosaicism
Less
Chromosome 21 is one of 5 pairs of chromosomes known as _____ chromosomes (13,14,15,21,22) meaning they have short p arms composed of repetitive DNA sequence coding for _____ RNA
Acrocentric
Ribosomal
____ ____ are the most common type of translocation in humans. They involve the joining of two acrocentric chromosomes and there centromeres. In this process, the ____ ____ are lost. Fortunately the lost of the repetitive short arm will not be clinically significant
Robertsonian translocation
Short arms
_____ robertsonian translocation is when there is still enough information there it is just rearranged. we don’t have extra of a chromosome or complete loss of a chromosome
Balanced
C and D
The chromosome 21 and 14 are hooked together in a robertsonian translocation. There are 6 different ways it can segregate:
3 of the 6 gamete’s lead to miscarriage, the one that is viable and not normal is trisomy 21
______ robertsonian translocation does cause clinical significant. A physician the must study _____ chromosomes to make sure one of the parents is not carrying the robertsonian translocation in an in ____ form
Unbalanced
Parental
Balanced
____ of balanced robertsonian translocations lead to increased probability for pregnancy with trisomy 21
Carriers
The mechanisms giving rise to trisomy 21:
Extra copy of a sex chromosome do not lead to as severe ____ as trisomies of autosomes
Phenotypes
Most sex chromosome aneuploidy do not result in a visible _____. May cause developmental delays or behavior problems. Rarely are these karyotypes brought to medical attention
Abnormalities
One common feature of XXX, XXY, and XYY is tall stature due to _____ gene being located on the end of the short arm of both X and Y
SHOX
XXY causes _____ syndrome and usually does get brought to medical attention. Causes infertility, small testes, decreases testosterone, enlarged breast, delayed or incomplete puberty
Klinefelter
Monosomy X is loss of a sex chromosome, causing ____ syndrome (45X). Results in short stature, primary _____, web neck, scoliosis, edema, cardiac abnormalities, hypothyroidism, renal abnormalities. No ____ disability
Turner
Amenorrhea: reproduction problems
Cognitive
____ is very common in Turned Syndrome. Have to do more studies and look at the karyotype to determine the variability in cells
Mosaicism
Practice
