Analysis of Chromosomal Disorders in the Clinic - 2

Question 1

What does CMA stand for?

Answer 1

Chromosomal Microarray

Question 2

What is the function of CMA?

Answer 2

A generalized, genome-wide survey for imbalances

Question 3

What do the different colours stand for on the CMA.

Answer 3

Green = deletion in sample at that locus
Red = duplication in sample at that locus 
Yellow = balanced at that locus

Question 4

What causes normal neonatal jaundice?

Answer 4

Bilirubin is unconjugated (bilirubin is the breakdown of the haem)

Question 5

What does conjugated hyperbilirubinemia imply?

Answer 5

Liver or biliary disease

Buildup of bilirubin (problem expressing bilirubin into bile ducts)

Question 6

Name the symptoms/characteristics of Alagille syndrome.

Answer 6

Multiple malformations - biliary tract, heart, spine, eyes
Variable expressivity
A characteristic face - angular, long face, pointed chin, deep set eyes

Question 7

What causes the jaundice in Alagille syndrome?

Answer 7

Hypoplasia of the biliary tree - a developmental defect

Caused by mutations in one of two genes - JAG1 and NOTCH2

Question 8

List the diagnostic options for Alagille syndrome.

Answer 8

Sequence the JAG1 or NOTCH2 genes
Look for small scale deletions/duplications in genes
Look for larger deletions/duplications that encompass the JAG1 or NOTCH2 genes
Last choice above is method of choice for chromosomal microarray

Question 9

Describe the basis of chromosomal microarray.

Answer 9

Diagnoses genomic imbalance at high resolution.
Optical microscopic analysis is used rarely now
Accurate sizing of deletions and duplications
Substantially bridges the gap between chromosomal analysis and sequencing level analysis of genetic disorders

Question 10

What does the chromosomal microarray use?

Answer 10

Genomic DNA

Question 11

Describe how a chromosomal microarray occurs.

Answer 11

Looks for a balance in the genome of a test case & a control genome.
No need for metaphases
Differential labelling of patient & normal DNA
Hybridization of 1:1 mixture to a spotted DNA array (chromosomal microarray = Comparative Genomic Hybridization)
Detect relative difference in DNA content of test vs normal by differences in red: green fluorescence ratio