Genomic Technologies

Question 1

What is the best genetic test?

Answer 1

A three generation family history

Question 2

Why is identifying a specific mutation important?

Answer 2

As in cystic fibrosis, specific genetic etiologies of the disorder can cause some drugs to be effective vs not effective

Question 3

What the molecular resolution of FISH and what should you use at less than this?

Answer 3

100 kilobases, at less than this use next generation sequencing or targeted mutation analysis via Sanger sequencing.

Question 4

When is it recommended to use Array-based technologies for detection of chromosomal abnormalities?

Answer 4

1. Individuals with multiple anomalies but not specific to a defined syndrome
2. Developmental delay or intellectual disability
3. Stillbirths and miscarriages if there are congenital anomalies

Question 5

When is whole exon / whole genome sequencing indicated?

Answer 5

High suspicion of an unknown genetic disorder, exhibiting a phenotype of high genetic variability (i.e. intellectual disability), current testing has not found an etiology

Question 6

What is the primary limitation of next generation whole exon or genome sequencing?

Answer 6

Will likely find multiple sequence variants of unknown pathogenicity which need to be filtered. Every genome will have 50-100 heterozygous variants of genes known to cause disease

Question 7

What is a primary vs secondary finding?

Answer 7

Primary - pathogenic alteration in gene which was relevant to the test ordered
Secondary - incidental pathologic finding which was unrelated to the diagnostic test ordering

Question 8

What is the guideline for reporting secondary findings?

Answer 8

Minimum list of conditions in clinical exome and genome sequencing, includes 56 reportable conditions based on the fact that they are known pathogenic variants for which surveillance or treatment is available.

Patient must opt out during informed consent for WES/WGS.