A baby presents at a clinic with a severe neurodevelopmental disorder that you suspect may be caused by a de novo (sporadic) genetic mutation. Describe how you could identify candidate Single Nucleotide Polymorphisms (SNP) that may cause the disease, without having access to samples from the child’s parents or from any other family member. Briefly describe a different approach that you could use to identify Copy Number Variants (CNV)

question

identifying SNPs and CNVs Without Parental Samples

layout

aspects,details

aspects

Scenario
Goal
Approach for SNPs
Variant Filtering

        Prioritization Tools

        Databases
        Approach for CNVs
        CNV Interpretation

Scenario

Baby with severe neurodevelopmental disorder; no parental/family samples.

Goal

Identify candidate de novo variants (SNPs and CNVs).

Approach for SNPs

Use Whole Genome or Whole Exome Sequencing.

Variant Filtering

• Exclude common variants (e.g. in gnomAD).
  - Focus on rare, likely damaging variants.

Prioritization Tools

• SIFT, PolyPhen (predict pathogenicity).
  - Evolutionary conservation.

Databases

OMIM, ClinVar, HGMD.

Approach for CNVs

Array CGH or depth-of-coverage analysis from WGS/WES.

CNV Interpretation

Use CNV databases (e.g., DECIPHER) to assess pathogenicit