C. Exome Seq. & Mendelian Disorders Flashcards
What are the main objectives of re-sequencing?
a. Discovery of novel mutations (rare Mendelian disease)
b. Genotyping of known variants (shared within a population) ex. Breast-cancer genes.
Features of resequencing?
a. Straightforward: by mapping (to find the best match in ref. seq.)
b. High reproducible: by high-depth sequencing (~ 40X)
c. Effective diagnosis: replacing cumbersome biochemical methods used in clinics (ex. amniocentesis test - karyotyping)
How is resequencing straightforward?
by mapping (to find the best match in ref. seq.)
How is resequencing highly reproducible?
High reproducible: by high-depth sequencing (~ 40X)
How does resequencing contribute to effective diagnoses?
Resequencing replaces cumbersome biochemical methods used in clinics (ex. amniocentesis test - karyotyping)
Minimal _____ coverage necessary for making reliable genotype calls (diploid)
Minimal 10X coverage necessary for making reliable genotype calls (diploid)
Which kinds of discordant reads support translocation-type of SVs?
?
How to call variants and kinds of variants collected by re-sesequencing?
Each read as one observation: high coverage –> precise calls
Small variants
SNPs (single nucleotide polymorphisms) Small Indels (insertion- deletions)
Large variants
CNVs (copy number variations), SVs (Structural variations)
- Use of discordant paired-end reads to collect SVs
How to distinguish benign and severe as 4-5 million variants are found in each individual?
By exome sequencing, which reduces the cost of sequencing. But its set-up requires large investment.
What is Exome?
Exome (protein-coding) + other identified genes (15 - 20 thousands)
equilibrated frequency distribution (p, q, r, etc.) can be used for measuring base- position-specific selection pressure
MAF can be used
