Rare disease common variants hypothesis

Beacon 1STEP 1: Assemble disease cohort

  • Assemble a disease or clinical trial cohort of 100 – 1, 000 cases.
  • EXAMPLE – Consider that Disease X is caused by genetic variants in 3 different genes (Genes X1, X2, X3), wherein each patient has a mutation in only 1 of these 3 genes (i.e., there are 3 genetic subtypes of Disease X).
  • [NOTE: In actuality, >20 genes may be independently causing a common disease.]

STEP 2: Perform genome-wide CNV analysis

  • Perform high-resolution genome-wide CNV analysis
  • Identify CNV ‘beacons’ – CNVs that occur exclusively or at far lower frequency in controls vs. cases – using PDx’s Normal Variation Engine® database of CNVs generated on healthy subjects.
  • EXAMPLE – Disease X is dissected into 3 subtypes (3 genes) with disease-associated CNVs (colored bars) to solve:
  • Gene X1, 5 of 13 cases
    Gene X2, 1 of 5 cases
    Gene X3, 3 of 6 cases

STEP 3: Perform targeted sequencing

  • Perform targeted sequencing of CNV-identified genes to find pathogenic SNVs (indels, etc.).
  • Alternatively, can identify pathogenic SNVs in exome and whole genome data via targeted interpretation of CNV Beacon® genes.
  • EXAMPLE – Disease X is further dissected by identifying disease-associated SNVs (colored vertical lines) and, combined with CNVs, solves:
  • Gene X1, 13 of 13 cases
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Popular Q&A

What disease was rare 50 years ago but is a common killer today?

I think Diabetes which was uncommon 50 years ago, has become a 'Silent Killer' today. With more and more people succumbing to this deadly disease, this might turned out in epidemic proportion in India by 2020,as per WHO's prediction. As Diabetes affects lung,eye,kidney and foot,people are falling prey due to liftstyle change, stress and other factors and more and more people carrying this disease without their knowing it.

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