Next generation sequencing was used to determine the inheritance pattern and risk of recurrence for two brothers with intellectual disability and autism features. Exome sequencing revealed an autosomal recessive trait, meaning their sister is a carrier but healthy brother is not, so there is a risk of recurrence in the family. Clinical testing including genetic panels, biochemical tests, and chromosome microarray had all been normal. Exome sequencing allowed clinicians to determine the mode of inheritance and risk level for family members.

1. Next Generation Sequencing
Clinical Examples 1.0In this tutorial we’re going to briefly go through some of the Clinical applications of Next Generation Sequencing and how it can be useful in determining inheritance patterns, distinguishing diagnosis between patients, and assessing the risks of an illness reoccurring.

2. Next Generation Sequencing can be used in a variety of places ranging from the clinical setting to a laboratory setting.

3. Clinical Example So in this first clinical example is one of [Read Slide]. In this case the 2
brothers have a healthy brother and sister are wondering what the risk is of their own children inheriting the disability. NGS, specifically Exome Sequencing, was used to determine risk of recurrence in the family
• 22 and 24 year old brothers:
– Intellectual Disability
– Severe self-injurious behaviors, autistic features
– Spastic Diplegia

4. Their molecular, cytogenetic, and biochemical conditions were tested and were concluded to be normal .
• Molecular/Cytogenetic:
– Karyotype
– Fragile X
– SNP Chromosome Microarray
– Mitochondrial DNA Sequencing
– XLMR Panels (>90 genes)
• Biochemical:
– Amino acids, organic acids
– Lactate, pyruvate
– Lysosomal enzyme panel
– 7-Dehydrocholesterol
– Very long fatty acids
All Results
Normal

5. Exome Sequence Results

6. Results of Diagnosis
Clinicians were able to:
• Determine the inheritance pattern of the
disorder
– Autosomal recessive trait, not an X-linked trait
• Determine risk of recurring in healthy siblings
– Sister carries the genes, Healthy brother does not.– So it is possible that there could be a recurrence in the family.

7. Works Cited
DeFrancesco, Chris. "News Release." Partnership to Deliver Gains in Medical, Dental
Research. N.p., 28 Sept. 2009. Web. 30 June 2014.
<http://today.uchc.edu/newsreleases/2009/sep09/partnership.html>.
Gonzalez, Kelly. "Making Sense of NextGen Sequencing." Ambry Genetics. N.p., n.d.
Web. 27 May 2014.
<http://www.ambrygen.com/sites/default/files/pdfs/NERRG_4-10-
12_Making_Sense_of_NetGen_Sequencing_KG(3).pdf>.
Schug, Jonathan. "Next Generation Sequencing Core." Next Generation Sequencing.
N.p., n.d. Web. 30 June 2014.
<http://www.med.upenn.edu/cores/NextGenerationSequencingCore.shtml>.
"University of Wisconsin–Madison Biotechnology Center." UWBC DNA Sequencing
Facility. N.p., n.d. Web. 30 June 2014.
<http://www.biotech.wisc.edu/services/dnaseq>.