Genomics in Modern med

Question 1

_______ is a new, structured approach to disease discovery, diagnosis and management that prominently features next-generation sequencing and analysis

Answer 1

Genomic medicine

Question 2

\_\_\_\_\_\_\_
•Gene by gene, exon by exon sequencing
•Multiplexing can accommodate small panels
•Time consuming
•Limited to known genes/regions
Gold standard of genomic testing

Answer 2

Sanger PCR

Question 3

_____: can do more than 1 gene or exon at a time

Answer 3

Multiplexing

Question 4

_____ = Technologies that permit rapid interrogation of DNA, up to and including entire genomes, via massively parallel sequencing
•Technology took shape in early 2000s
•The term emphasizes a distinction from initial approaches that involved sequencing of one DNA strand at a time.
•Decreasing cost and comparatively rapid results are creating a paradigm shift in genetics; particularly in monogenic disease.

Answer 4

Next Generation Sequencing (NGS)

Question 5

DNA changes
•Common: found in >1% of population aka SNPs (can be advantageous/silent/risk associated)
•Rare: <1% of population (all of the above + pathogenic)
•Account for about 75% of all DNA changes
•Found in about 1 in every 100 to 300 nucleotides

Answer 5

Single nucleotide variants

Question 6

DNA Changes:
•Insertions and deletions of up to 50-100 nucleotides
•Occur 1/10th as often as SNV
•90% are 1-10 nt in length

Answer 6

In-del

Question 7

DNA Changes:

•Least frequent but large so, in total, affect the most nucleotides

Answer 7

Copy number variants: CNVs

Question 8

____ is the process of selection of DNA that you want and don’t know

Answer 8

Enrichment

Question 9

While there are subtle differences between tests, all samples undergo _____

Answer 9

library prep

Question 10

The goal of library preparation is add _____ and _____ to identify individuals

Answer 10

add primers and barcodes

Question 11

• Involves selecting out specific regions of interest for sequencing using capture probes
• Pooling allows for samples to be mixed together beforehand
• Allows for more sequencing of targeted regions
• Decreases costs and time per sample

Answer 11

Enrichment

Question 12

• Sample preparation and sequencing are only a small part of the process
• Utilize custom and commercial software solutions

Answer 12

Bioinformatics

Question 13

______ allows for diagnosis of atypical presentations that would not have otherwise be considered

Answer 13

Next Generation sequencing (NGS)

Question 14

• Inherited syndromes that affect ______
• Mineralization Defects (PHEX, DMP1, FGF23)
• Ectodermal dysplasias

Answer 14

tooth development

Question 15

_____ is seen in the following gene: PAX9

Answer 15

•Hypo/Oligodontia

Question 16

• Several forms of autosomal dominant enamel dysplasia

* Enamel hypoplasia or hypocalcification

Answer 16

Amelogenesis imperfecta

Question 17

At least 18 genes associated with non-syndromic AI, including what 3?

Answer 17

• AMELX (Amelogenin)
• AMTN (Amelotin)
• ENAM (Enamalin)