Analysis of Chromosomal Disorders in the Clinic - 2 Flashcards
(21 cards)
What are the aims of the analysis of chromosomal disorders?
• Compare and contrast conventional cytogenetics with newer methods to detect genomic imbalance
• Appreciate that broad range of copy number anomalies exist in health and disease
• Understand different methods to assay for deletions and duplications of different sizes in the genome
• Understand the principles and uses of chromosomal microarray
What percentage of spontaneously aborted fetuses have chromosomal abnormalities?
50%
What percentage of stillborn babies have chromosomal abnormalities?
10%
What percentage of newborn babies (neonates) have chromosomal abnormalities?
0.7%
What is the modern way to look for chromosomal imbalance?
Chromosomal MicroArray
What are the colors indicating on a chromosomal microarray?
• Green = deletion
• Red = duplication
• Balanced at that locus
What is a challenge when interpreting chromosomal microarray results?
Distinguishing pathogenic copy number variants from ‘normal’ background variation seen in the general population
What condition is characterized by conjugated hyperbilirubinaemia, heart defects, and spinal anomalies?
Alagille syndrome
What are the diagnostic options for Alagille syndrome?
- Sequence the JAG1 or NOTCH2 genes
- Look for small scale deletions and duplications in genes
- Look for larger deletions or duplications that encompass the JAG1 or NOTCH2 genes
What does chromosomal microarray diagnose?
Genomic imbalance at high resolution
What technology has largely replaced optical microscopic analysis in cytogenetics?
Chromosomal microarray
What does the term ‘de novo’ refer to in genetic analysis?
A mutation or deletion that arises spontaneously and is not inherited from the parents
What does a 3 Mb deletion on chromosome 20 indicate in relation to Alagille syndrome?
It is highly likely to be causative of the syndrome
What is the penetrance of the chr22q11 duplication associated with developmental neuropsychiatric traits?
Approximately 20%
True or False: Genetic factors can be susceptibility factors even if strong associations exist.
True
Fill in the blank: The chromosomal microarray uses genomic _______.
DNA
What is a critical consideration when interpreting high-resolution chromosomal microarray results?
Background variation
What is the relationship between a unique genetic variant and its phenotype?
It can be interpreted by asking if it segregates with the phenotype or has arisen de novo
What is Cri du chat syndrome associated with?
Terminal and interstitial deletions of 5p
What variant type requires caution in interpretation due to its uncertain significance?
Copy number variants
What is the importance of family history in genomic analysis?
It can be very valuable for interpretation of rare variants
