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Cytogenetics - Coggle Diagram
Cytogenetics
Current diagnostic technologies
Genomic Sequencing
Comparative Genome Microarray
SNP Microarray
type of chromosome microarray
Detects variants and copy number
consanguinity
parental disomy
can express recessive trait when only one parent is carrier
two alleles, but both come from one parent
SNPs of clinical interest
Limitations
Only detects certain SNPs
Detects genetic vairiants at numerous predetermined loci
comparative genome hybridization CGH
Because these are so wide spread in their search, they may yield unexpected findings
Comparing a patient against reference DNA to identify differences
G-banded chr.
FISH (Floresence In Situ Hybridization)
Benefits
Rapid analysis for high-risk pregnancies
No need for chromosome spread (~48 hour turnover)
Gotta purchase florescent fragments of DNA that are hybridized into the gene
Really quick turnover
Clinical applications of FISH
Need to be suspicious of what you're looking for to order probes
Suspected deletion/duplication (parental follow up of anomaly found in child)
aneuploidy
sex chr.
Limitations
See only region complementary to probe
May not detect low level mosaicism or structural chromosomal abnormalities
MS-MLPA (imprinting disorders)
Recognize features of major aneuploidies
Turner syndrome 45,XO
90% w/ amenorrhea
Short stature
Normal intelligence
30% webbed neck
Aneupoloidy means diff # chromosomes
Nomenclature
Nomenclature: modal number, sex chromosomes, +chromosome
Autosomal trisomies often are lost in gestation
Trisomy 21 (Down syndrome)
Common features in neuborns:
congenital heart defects
flattened face
epicentral folds
Developmental delays
Mild to moderate ID
Edwards Syndrome
Often stillborn, rare survival 6 months
20-40% survival first month
10% survival first year
Identify major structural features of chromosomes
Chromatin is composed of DNA, histones and other protiens
chromosome structure
Telomeres
Specialized structures at the end of chromosomes
Stalk
q arm = long arm
p arm = short arm
bands are numbered from the centromere going outward
Satellite
Location of the centromere defines chromosome morpholoty
Metacentric
submetacentric
Acrocentric
G-banded chormosomes
Stretched out chromosomes to see bands
provides an overall view of the entire genome
mosaicism
deletions >5Mb
some translocations
aneuploidy
ring, marker, isochomosomes
Structural variations
Additional rearrangements
Isochromosomes
Ring chromosomes
~6% of Turner syndrome is ring chr.
short stature
ovaries w/ few/absent follicles - amenorrhea
Marker chromosomes
Inversions
nomenclature
46,XXinv(2)q15q36)
Details
outcomes related to whether centromere is part of inverted segment
paracentric - within arm of chormocome
may need to nonviable offspring
pericentric - includes chromosome
may lead to risk of child w/ duplication (dup) and deletion (del)
can lead to unbalanced gametes
balanced rearrangement, often no phenotype
two break intrachormosomal rearrangement
material between breakpoints flips over
Translocations (t)
Robertsonian (rob)
q arm fusion of acrocentric chorosomes
q10;q10 means robertsonian translocation
yield metacentric or submetacentric chromosome, often dicentric (break points at or near centromere (q10)
carriers often unaffected
short p arms lost
long arms remain intact
risk of infertility or children w/ unbalanced translocations
Balanced
no net loss or gain of genetic material w/ non homologous chormosomes
increased risk of miscarriage or children w/ abnormalities
chromosomes are always named by source of centromere
often unique to families
recurrence risk influenced by:
ascertainment
size of translocated degment
chromosomes/genes affected
unbalanced
arise by fertilization of a gamete bearing a balanced translocation
result may be 46 chr. but w/ monosomy and trisomy for some regions
most are actually normal and balanced as far as recurrence is concerned
Deletions and Duplications
Deletions
Velocardiaofacial syndrom (VCFS)/DiGorge syndrome
Duplications
Charcot-Marie-Tooth Type 1A (CMT1A)
Muscle atrophy
Types
Interstitial - between the termini
terminal - extends to end
May result in
contiguous gene syndrome
loss/duplication of multiple genes contribute to trait
meiotic non-allelic homologous recombination of low copy repeats is primary mechanism by which del and dup arise
Duplications often cause milder issues than deletions
Factors that affect pathogenicity of anomalies
mosaicism - extent, timing, location
different cell types differ due to post-zygotic event
presence of two or more genetically different cell varieties
phenotypes vary greatly
Mosaic DS has milder traits than full DS
extent of genome affected
locaition in genome - what is lost or gained or changed
